CNS STIMULANT - s1.fkh.unair.ac.ids1.fkh.unair.ac.id/images/PPT/Sedatif n CNS Stimulant. Iwan...
Transcript of CNS STIMULANT - s1.fkh.unair.ac.ids1.fkh.unair.ac.id/images/PPT/Sedatif n CNS Stimulant. Iwan...
Dr Iwan Sahrial Hamid MSi Drh
SEDATIF-HIPNOTIC
Reduce Stimulation CNS
CNS STIMULANT
Increase Stimulation CNS
A stimulant is a drug that speeds up activities of the CNS
A depressant is a drug that slows brain and body reactions
Stimulants increase Depressants decrease
HR
BP
RRRelax muscle tensionLower alertnessCause drowsiness
Increase Motor ActivityIncrease AlertnessDecrease need for Sleep
Mild CNS
Moderate CNS
SevereCNS
bull Inability to focusbull Decreased interest in
surroundings
bull Decreased perception of heat or cold
bull Sleepbull Drowsiness
bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness
bull Decreased fatiguebull Mental alertness bull Wakefulness
bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity
bull Cardiac dysrhythmiasbull Seizures bull Confusion
Low dose
Over dose
Higher dose
increase dose
bull SEDATIVES ndash reduce anxiety and exert a calming effect
bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep
Increase Sedative-hypnotic Dose
CN
S ef
fect
s
Possible selective anticonvulsant and muscle-relaxing activity
Sedation
Hypnosis
(Benzodiazepines) Anesthesia
Medullary depression
(Barbiturates) Coma
Relationship between dose of benzodiazepines and barbiturates and their CNS effect
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
A stimulant is a drug that speeds up activities of the CNS
A depressant is a drug that slows brain and body reactions
Stimulants increase Depressants decrease
HR
BP
RRRelax muscle tensionLower alertnessCause drowsiness
Increase Motor ActivityIncrease AlertnessDecrease need for Sleep
Mild CNS
Moderate CNS
SevereCNS
bull Inability to focusbull Decreased interest in
surroundings
bull Decreased perception of heat or cold
bull Sleepbull Drowsiness
bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness
bull Decreased fatiguebull Mental alertness bull Wakefulness
bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity
bull Cardiac dysrhythmiasbull Seizures bull Confusion
Low dose
Over dose
Higher dose
increase dose
bull SEDATIVES ndash reduce anxiety and exert a calming effect
bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep
Increase Sedative-hypnotic Dose
CN
S ef
fect
s
Possible selective anticonvulsant and muscle-relaxing activity
Sedation
Hypnosis
(Benzodiazepines) Anesthesia
Medullary depression
(Barbiturates) Coma
Relationship between dose of benzodiazepines and barbiturates and their CNS effect
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Mild CNS
Moderate CNS
SevereCNS
bull Inability to focusbull Decreased interest in
surroundings
bull Decreased perception of heat or cold
bull Sleepbull Drowsiness
bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness
bull Decreased fatiguebull Mental alertness bull Wakefulness
bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity
bull Cardiac dysrhythmiasbull Seizures bull Confusion
Low dose
Over dose
Higher dose
increase dose
bull SEDATIVES ndash reduce anxiety and exert a calming effect
bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep
Increase Sedative-hypnotic Dose
CN
S ef
fect
s
Possible selective anticonvulsant and muscle-relaxing activity
Sedation
Hypnosis
(Benzodiazepines) Anesthesia
Medullary depression
(Barbiturates) Coma
Relationship between dose of benzodiazepines and barbiturates and their CNS effect
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
bull SEDATIVES ndash reduce anxiety and exert a calming effect
bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep
Increase Sedative-hypnotic Dose
CN
S ef
fect
s
Possible selective anticonvulsant and muscle-relaxing activity
Sedation
Hypnosis
(Benzodiazepines) Anesthesia
Medullary depression
(Barbiturates) Coma
Relationship between dose of benzodiazepines and barbiturates and their CNS effect
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Increase Sedative-hypnotic Dose
CN
S ef
fect
s
Possible selective anticonvulsant and muscle-relaxing activity
Sedation
Hypnosis
(Benzodiazepines) Anesthesia
Medullary depression
(Barbiturates) Coma
Relationship between dose of benzodiazepines and barbiturates and their CNS effect
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Why prescribed
1048698 Anxiety
1048698 Short term problems (performance)
1048698 Long term problems (panic GAD PTSD)
1048698 Sleep problems
1048698 Muscle relaxants
1048698 Depression
1048698 Only 20 of prescriptions done by
psychiatrists
1048698 Benzodiazepine is in top 10 of all medical
prescriptions
SEDATIVE - HIPNOTIC
Generalized anxiety
disorder (GAD)
Posttraumatic stress
disorder (PTSD)
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
General Function
1048698 Decrease CNS responding
1048698 Lower anxiety
1048698 General sedation
1048698 Some cognitive slowing
1048698 Major therapeutic use is to relieve anxiety
(anxiolytics) or induce sleep (hypnotics)
1048698 Hypnotic effects can be achieved with most
anxiolytic drugs just by increasing the dose
1048698 All of the anxiolyticssedative-hypnotics should
be used only for symptomatic relief
1048698 All the drugs used alter the normal sleep cycle and
should be administered only for days or weeks
never for months
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Classifications
1048698 Barbiturates (BARBs)
1048698 Benzodiazepines (BZDs)
BENZODIAZEPIN
Appear Effects
Hypnotic Sedation Muscle Relaxation
Anxyolitic and decrease convultion with different
Potention
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Effects of benzodiazepinebull On increasing the dose sedation progresses to
hypnosis and then to stupor
bull But the drugs do not cause a true general anesthesia because
-awareness usually persists
-immobility sufficient to allow surgery cannot be achieved
bull However at preanesthetic doses there is amnesia
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Mechanism of action
Benzodiazepines (BDZs) bind to the gamma
sub-unit of the GABA-A receptor Their binding
causes an allosteric (structural) modification of
the receptor that results in an increase in GABA
A receptor activity BDZs do not substitute for
GABA which bind at the alpha sub-unit but
increase the frequency of channel opening
events which leads to an increase in chloride ion
conductance and inhibition of the action
potential
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Figure 1 Figure and tables index
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Hypothetical model for the excitatory and neurotoxic action of
uremic retention solutes on the central nervous system The model
focuses on reported effects on GABAA receptor (GABAA-R) NMDA-
type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel
(VGCC) but may include other neuroexcitatory effects of these solutes
The excitatory neurotransmitter L-glutamate is released from presynaptic
terminals and binds to AMPA and NMDA receptors GABAergic
interneurons provide synaptic inhibition through activation of GABAA-R
and chloride influx (resulting in inhibitory hyperpolarization of the
membrane) In the presence of GSA or other excitatory uremic retention
solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)
activated lifting the voltage dependent block from NMDA-Rs Ca2+
influx through NMDA-R ionophores and VGCCs activates postsynaptic
Ca2+-triggered events These may include activation of nitric oxide
synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading
to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic
effects of NO and activation of presynaptic VGCC could increase
excitatory glutamate release
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Benzodiazepin Aktivasi GABA a
Aktivasi Reseptor GABA a
Pembukaan kanal Cl- Membran Sel Saraf
Masukknya Ion Klorida Ke Dalam Sel Saraf
Peningkatan Potensial Elektrik Sepanjang Membran Sel
Hiperpolarisasi Hambatan Eksitasi
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
BDZ (Benzodiazepin) Pharmacodynamics
1048698 Benzodiazepines act on GABAa
receptors
GABA receptor
A pentameric protein
Forms an ionotropic receptor complex
Consists of several subunits designated
Alpha (mainly responsible for the
pharmacology of the receptor)
Beta
Gamma (required for high affinity
benzodiazepine binding)
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Anxiolytic and
Sedative-hypnoticsGeneric Name Trade Name
Chlordiazepoxide Librium
Clonazepam Klonopin
Diazepam Valium
Flurazepam Dalmane
Lorazepam Ativan
Oxazepam Serax
Temazepam Restoril
Triazolam Halcion
Non-
Benzodiazepine
anxiolytics
and hypnotics
Buspirone BuSpar
Chloral hydrate Noctec
Zolpidem tartrate Ambien
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Medication
Dose (mg)
Onset of
action
(minutes)
Half-life
(hours)
Metabolic
pathway
Duration of
hypnotic
effect
Estazolam 1-2
(elderly )
05-1 mg
15-30 8-24 Oxidation Intermediate
Flurazepam 15-30 60-120 47-100
including
metabolites
Oxidation Long
Quazepam 75-15
(elderly
75 mg)
20-45 25-41
including
metabolites
Oxidation Long
Temazepam 15-30
(elderly
75-15 mg)
45-60 10-20 Conjugation Intermediate
Triazolam 0125-025
(elderly
15-30 16-54 Oxidation Short
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
PHARMACOKINETICS
bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation
bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)
bull After metabolism these are conjugated and are excreted via kidney
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
KINETIK
Absorpsi Biasanya diberikan secara peroral
absorpsinya cepat tergantung dari lipofilisitas
obat yang berbeda (Triazolam Diazepam
Lebih Cepat)
Distribusi
Lebih mudah larut lemak lebih cepat memasuki
CNS Semua Sedatif-Hipnotik menembus
Plasenta Barrier tidak dianjurkan pada masa
kebuntingan
Kloralhidrat meningkatkan efek antikoagulan
dari Warfarin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Biotransformasi
Hampir semua Benzodiazepin mengalami
oksidasi mikrosomal (Fase I) Metabolit
Aktif yang waktu Paruhnya lebih lama
Reaksi Fase II Konjugasi oleh Glucuronosyl-
Transferase ekskresi urine Glucoronide
Ekskresi
Metabolit larut air diekskresi lewat ginjal
Penurunan fungsi hepar menurunkan proses
klirens
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Classification
1 Long acting barbiturates (More than 8hours) ndash Barbitone
Barbital sodium
Phorobarbital Mephobarbital
2 Intermediate acting barbiturates (4 - 8hours) ndash Allo
barbital hexobarbital
pento hexital sodium
3 Short acting barbiturates (less than 4 hours) ndash Seco
barbital hexobarbital
Pento barbital cyclo barbital
4 Ultra short acting barbiturates ( I-V anaesthetics) ndash
Thiopental sodium
Metho hexital sodium
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Mechanism of action Barbiturates either have a Gama amino butyric acid
(GABA) like action or enhance the effect of GABA aninhibitory transmitter
The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters
When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation
Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
EFEK BARBITURAT
Pada CNS
Dicapainya semua semua tingkat depresi
sedasi ansiolitik hipnosis bbrp tingkat
anestesia koma sampai dengan kematian
Efek Hipnotik dicapai 20-60 menit
Efek Anestesi umum Tiobarbital Oksibarbital
Efek Antikonvulsi Fenobarbital Mefobarbital
Menyerupai kerja Benzodiazepin dosis lebih
tinggi Agonis GABA Depresi lebih berat
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
MODEL STIMULASI
BLOKADE SISTEM PENGHAMBATAN
(STRIKNIN METRAZOL)
PENINGKATAN RANGSANGAN SINAP
(DOKSAPRAM NIKETAMID XANTIN
DERIVED)
Agents which remove inhibition from CNS
neurons increase synaptic excitation
or alter axonal membrane properties
Net result is CNS stimulation
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Pharmacological properties
Produces CNS excitation by blocking
glycine-mediated postsynaptic
inhibition
Sequence of strychnine effects
Tightness of neck and jaw muscles
Hyperreflexia
Tonic extensor thrusts
Tetanic symmetrical convulsions
(opisthotonus)
Respiratory arrest
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
STRIKNIN
ACTION Kompetitif Antagonis Terhadap Inhibitor
Transmiter GLYSIN (Penghambatan
Pasca Sinap)
Konvulsan Spinal Rangsangan pada Medula Spinalis
Rangsangan pada Medula Oblongata Efek pada
Pusat Vasomotor
Peningkatan Tekanan Darah
Peningkatan Tonus Otot
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Sifat Kejang
Ekstensi Tonik Seluruh Tubuh dan Ekstremitas
Kontraksi Ekstensor Simetris yang diperkuat
Rangsangan Sensorik
( Pendengaran Penglihatan dan Perabaan)
KINETIK
Absorbsi Mudah di Tempat Injeksi
Masuk Sirkulasi Masuk Jaringan
Segera Ekskresi Lewat Urine (Ekskresi
Lengkap 10 Jam)
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
GEJALA KLINIS
Kaku Otot Muka dan Leher
Hiperekstensi
Kontraksi Otot Diafragma Depresi Napas
Akumulasi Asam Laktat dalam Plasma
Asidosis Metabolik
PENTILENTETRAZOL (METRAZOL)
ACTION
HAMBATAN SISTEM GABA ndash ERGIC
EKSITABILITAS SSP MENINGKAT
EXCITATORY
Efeknya Lebih Kecil Dibanding Pikrotoksin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
KINETIK
Absorbsi cepat Distribusi merata
Metabolisme di Hepar cepat
Ekskresi 75 di Urin dalam
keadaan Tidak Aktif
METIL FENIDAT
ACTION Efek Penglepasan Norefineprin
Simpatomimetik Berkurang
Termasuk α2 Agonis
Efek Lebih Menonjol pada Aktivitas
Mental Mirip Amfetamin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
α2 AGONIS
Efek Penglepasan Norefineprin
Aktivasi Prot G(i)
Adenilsiklase
ATP cAMP 5AMP + PI
Aktivasi Kanal K+ Hiperpolarisasi
pada Neuron Mienterik Kolinergik
Pelepasan Asetilkolin
Relaksasi Otot Polos
Aktivasi Kanal Ca2+
Sekresi Insulin
Rangsangan
Simpatis dari
CNS
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam
Distribusi di Otak Lebih Besar
Metabolisme 80 Asam Retanilat
Ekskresi Melalui Urine
DOKSAPRAM DAN NIKETAMID
ACTION
Rangsangan pada seluruh serebrospinal
Meningkatkan derajat Perangsangan
Pada dosis kecil IV Aktivitas Kemoreseptor
karotis dan Neuron Pusat Napas Tidal Volume
Perangsangan Pusat Napas
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Direct acting stimulants
Increase nueronal excitability by
decreasing neuronal recovery time or by
increasing responsiveness to excitatory
neurotransmitters eg doxapram
(Dopram)
Claimed to be a specific respiratory
stimulant and to be useful in
treatment of drug induced respiratory
depression Supportive treatment is
better Sometimes used in anesthesia
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Analeptics ndash Xanthines Derived
bull Pharmacological properties
ndashMechanism of action ndash act as
antagonists at adenosine receptors
Adenosine receptors are located on
presynaptic terminals of noradrenergic
neurons and blocks NE release So
caffeine increases NE release
ndashInhibition of phosphodiesterase occurs
but only at very high doses
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
bull Pharmacological properties
ndashCNS ndash stimulate cortex first then
medulla and spinal cord at high doses
ndashDiuresis
ndashStimulation of cardiac muscle
ndashSmooth muscle relaxation
ndashSecretion
ndashSkeletal muscle - diaphragm
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
bull Adverse effects
ndashAt 1 g dose of caffeine (12 cups
coffee)
bullInsomnia excitement mild
delirium sensory disturbances
bullIncreased heart rate
bullIncreased respiration
ndashAt higher doses (10 g)
bullClonic convulsions rarr death
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
bull Adverse effects
ndashChronic use in pregnant women
may increase rate of spontaneous
abortion
ndashTolerance and physical dependence
can occur Withdrawal symptoms
include lethargy irritability and
headache
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN
ACTION
Efek Perangsangan CNS Kuat Kontraksi Otot Jantung
Efek Diuresis
Relaksasi Otot Polos Bronkus
Menghambat Fosfodiesterase
Mirip Agonis β2 Adrenergik (Salbutamol)
Pada CNS Terutama Teofilin dan Kafein Untuk Depresi
Med Oblongata Merangsang Pusat Napas Kepeka-
an Terhadap CO2
Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah
Perifer
Meningkatkan Frekuensi Jantung
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Stimulasi Pusat Vasomotor dan Stimulasi Miokard
Tekanan Darah
Stimulasi Pusat Vagus dan Vasodilatasi
Tekanan DarahEfek Resultan
Sedikit Tekanan Darah
Mekanisme Seluler
Translokasi Ion Kalsium Intra seluler
Peningkatan Siklik AMP dan GMP
Blokade Reseptor Adenosin
KINETIK
Absorbsi Cepat Peroral PE Suppositoria
Peak Plasma Teofilin 2 jam Kafein 1 jam
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin
Distribusi
Seluruh Jaringan Trans Plasenta Protein
Binding
Metabolisme Hepar
Ekskresi Urine Dalam Bentuk Asam Metil urat
atau Metilxantin