Medicines suppressing the cental nervous system (CNS ...
Transcript of Medicines suppressing the cental nervous system (CNS ...
Medicines suppressing the cental
nervous system (CNS depressant)
NATIONAL PHARMACEUTICAL UNIVERSITY
Department of Pharmacology
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Neuroleptics
(ANTIPSYCHOTIC MEDICINES)
Neuroleptics are psychotropic medicines that are
able to reveal the inhibitory action on the CNS (without
consciousness disturbing) eliminate hallucinations,
delirium and stop the psychomotor excitation (motor and
speech).
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Classification of neuroleptics
Derivatives of
phenotiazine butyrophenone Thioxanthene *,
dibenzodiazepine #,
benzamide &,benzisoxazole $
Chlorpromazine
Levomepromazine
Perphenazine
hydrochloride
Droperidol
Haloperidol
Clozapine #
Chlorprothixene *
Sulpyrid &
Risperidone $
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Pharmacological action
Antipsychotic effect (elimination of delusions, aggression)
is associated with blockade of dopaminergic D2 receptor reticular
formation (removed activating influence on the cortex of the
brain), nuclei, midbrain, limbic system, hypothalamus. With the
same linked primary and side effects - extrapyramidal disorder, a
syndrome similar to Parkinson's disease.
Potential action is caused by blockade a-AR and reticular
formation.
Antiemetic effect is related to the blockade of dopaminergic (D2)
and serotonin receptors "trigger zone“ of medula oblongata and
termination of the signals in the emetic center.
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The Hypothermic effect is the result of adreno- and
serotonin receptors blockade and, therefore, decrease of the activity
of the hypothalamic thermoregulation centres (decrease of the heat
production and increase of the heat emission).
The Antihistamine effect implemented by the blockade of H1-
histamine receptors.
The Hypotensive effect - the result of blockade of AR and a-
dofaminoretseptors in the hypothalamus and peripheral vessels.
The Neuroleptic (weakness, drowsiness, paralysis of will", motor
inhibition) action - blockade of central and a-AR reticular
formation, limbic system, hypothalamus.
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Effects and related indications
Pharmacodynamics (effects) → Indications
Antipsychotic Psychosis (schizophrenia etc.)
Potentiating
(for medicines that suppress CNS)
Neuroleptanalgesia, potentiation
of narcosis
Anti-emetic Uncontrolled vomiting of the
central genesis (in pregnant women
with anti-tumor therapy)
Hypothermic Controlled hypothermia during
narcosis
Antihistaminic Severe neurodermitis
Hypotensive Severe forms of arterial
hypertension with psychomotor
excitation (chlorpromazine only)
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Side effects → Contraindications
Neuroleptic syndrome, drug-
induced parkinsonism, dyspepsia
Depression, parkinsonism
Derivatives of phenotiazine, butyrophenone, thioxanthene
called "typical" neuroleptics, as they lead to the development of
medicinal parkinsonism ( D2 receptor in the black substance and
striped body region)-extrapyramidal disorders.
Risperidone, clozapine are atypical neuroleptics
Side effects of typical neuroleptics and related
contraindications
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These new medications were approved for use in the 1990s.
Clozapine, asenapine, olanzapine, quetiapine, paliperidone,
risperidone, sertindole, ziprasidone, zotepine, and aripiprazole are
atypical antipsychotic drugs. With the discovery of clozapine in
1959, it became evident that this drug was less likely to produce
extrapyramidal effects (physical symptoms such as tremors,
paranoia, anxiety, dystonia, etc. as a result of improper doses or
adverse reactions to this class of drug) in humans at clinically
effective doses than some other types of antipsychotics. Clozapine
was categorized as the first atypical antipsychotic drug. This
category of drugs has also been of great value in studying the
pathophysiology of schizophrenia and other psychoses.
Atypical Antipsychotics,
or Second Generation Antipsychotic Drugs
The pharmacological “face” of neuroleptics
Antipsychotic effect :
Haloperidol Droperidol Closapine Chlorprothixene =
Chlorpromazine =Perphenazine hydrochloride=Sulpyrid
Levomepromazine
Potentiating effect:
Haloperidol Droperidol Levomepromazine Chlorpromazine.
Anti-emetic effect :
Haloperidol Perphenazine hydrochloride Droperidol
Sulpyrid Chlorpromazine
Neuroleptic effect :
Derivatives of phenothiazine = butyrophenone thioxanthene
Closapine Sulpyrid.
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TRANQUILIZERS
(ANXIOLYTICS, ATARACTICS, ANTIPHOBIC
MEDICINES)
Tranquilizers (in Latin tranquillare – „to make calm”)
are medicines that remove selectively fair, anxiety, emotional
tension increased restlessness and are used mainly in neuroses
and the related states.
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Classification of tranquilizers
Derivatives of benzodiazepines Derivatives of
diphenylmetanum and other
chemical groups
Diazepan Alprazolam
Phenazepam Lorazepam
Chlordiazepoxide Gidazepam
Hydroxysine*
Meprobamat
Medazepam, Gidazepam, Trimetosine are “day time”
tranquilizers as they cause less inhibition of CNS than other
medicines, therefore,they can be used in day time.
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The mechanism of action
They decrease the excitability of subcortical regions of
the brain (the limbic system, thalamus, the reticular formation,
the hypothalamus), that are responsible for emotional reactions,
inhibit the interaction between these structures and the brain
cortex.
Benzodiazepines stimulate mainly benzodiazepine
receptors and that leads to activation of GABA-receptors and
intensification of the inhibitory functions of GABA .
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Benzodiazepines
GABA
The mechanism of Benzodiazepines action
Ion
channel
Extracellular
compartment
Cytoplasm
Membrane
of neuron
Effects and related indications
Pharmacodynamics (effects) → Indications
Аnxiolytic Neuroses
Stress-protective Stress-reaction
Hypnotic Insomnia (especially caused by
negative emotions)
Sedative Neurogenic diseases
Anticonvulsant Convulsions (epilepsy)
Potentiating Premedication
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Side effects → Contraindications
Drowsiness, weakness,
disorders of attention and
locomotion, tolerance, addiction
Activities that require rapid
psychomotor reactions. Long-
term courses of treatment.
Increase of doses
Side effects and related contraindications
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The pharmacological «face» of tranquilizers
Medicines Tranquili-
zing effect
Addiction/
tolerance
Side
effects
Other effects
Phenazepam ++++ +/+ + Anticonvulsant, hypnotic, sedative,
spasmolytic (diazepam)Diazepam +++ +/+ ++
Chlordiaze-
poxide
++ +/+ +
Lorazepam ++ - + Accumulation, anticonvulsant, hypnotic
Alprazolam + - + Anticonvulsant, antidepressant
Gidazepam + - Anticonvulsant, potentiating, stimulating
Hydroxysi-
ne
- + Analgesic, myorelaxant, antiemic
Meproba-
mat
+ ++/+ ++ Anticonvulsant
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Sedative Medicines
Sedative medicines (in Latin sedatio is
calming) are medicines that cause a moderate
sedative effect as a result of decrease of CNS
excitability and its reactivity of different stimuli
The mechanism of action
They increase of the inhibitory processes in the
CNS and decrease of the excitability of the reticular
formation and the brain cortex.
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Classification of medicines
Plant
origin
Bromide compounds *
and Combined **
Persenum**
Valerian extract
Novo-passit**
Sodium bromide*
Corvalol** (Valocordin)
Valocormide**
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Pharmacodynamics (effects) → Indications
Sedative Neuroses, increased irritability,
neurogenic disease, insomnia
Stress-protective Stress-reaction
Potentiating Intensification of effects of CNS
depressants, the early stage of
hypertension
Side effects → Contraindications
Decrease of the mental and
physical activity, feeling of
fatigue, drowsiness
Activities that require rapid
psychomotor reactions
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Effects and related indications
The features of sedative medicines is the lack of
significant side effects because they are widely used in
outpatient practice and in elderly patients.
At long use drugs generates bromine "bromizm": general
retardation, drowsiness, weakening of memory, apathy,
decreased potency, tearing, cough, running nose, skin rash.
Treatment: immediately stop taking the drug, the
introduction of large numbers of sodium chloride (20 g per
day) and need to drink a lot.
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Pharmacological «face» of sedative drugs
Preparations EffectsComposition/other effects
Sedative Spasmolytic
Sodium
bromide
+++ Anticonvulsant
Urticae
Canine
Tincture
++
Valerian
extract
+ + Spasmolytic
Persen + + Mint, Melissa
Corvalol ++ + Phenobarbital, mint oil
Valocordin + + Sodium bromide, Convallaria,
Belladonna, Menthol
Novo-passit ++ + Guaphenesine, extracts of Crataegus,
Humulus, Hypericum, Milissa,
Passiflora, Sambucus
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Hypnotic medicinesDisorders of sleep (insomnia, hyposomnia) are one of the
states that are common and occur independently (primary
insomnia), and at the different somatic and psychiatric
pathologies (the secondary insomnia).
If the sleep disorder is repeated more than 4 times a week,
which requires pharmacological correction as insomnia
(violation of physiological rhythms in the CNS) leads to
overexcited, fatigue, exhaustion of the brain and, consequently,
to different forms of pathology of neurogenic origin.
Hypnotics are products that tend to restore the process of
falling asleep, sleep duration and depth of their violation.
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The mechanism of action
of sedative medicinesInhibit some brain structures (mainly cerebral cortex).
Weaken the activating reticular formation of the discharges in the
cerebral cortex.
In the mechanism of action of benzodiazepine and barbituric acid
an important part plays their relationship with benzodiazepine
receptors and barbiturate-benzodiazepine-GABA receptor
complex, leading to strengthening of the natural inhibitory
neurotransmitter GABA (gamma amino butyric acid)
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Hypnotics
Pharmacodynamics (effects) → Indications
Hypnotic Disorder of sleep
Potentiating Intensification of the effects of CNS
depressants
Sedative(low doses) Mild neuroses, neurotic syndrome
Side effects → Contraindications
Apathy, drowsiness, weakness Activities that require the rapid
psychomotor reactions
Most sleeping drugs causes the violation of the structure sleep
syndrome "aftereffect", "return", “withdrawal", physical and psychological
dependence, addiction, cummulation (especially barbiturates).
Closest to the ideal of sleeping drugs - zopiklon and zolpidem.
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Classification of medicines
Derivatives of
benzodiazepine,
barbituric acid
Derivatives of
cyclopyrrolone,
imidazopyridine,*
methylbutamide**
Combined medicines
Nitrozepam
Phenobarbital
Cyclobarbital*
Zopiclone
Zolpidem*
Bromisoval**
Reladorm
(cyclobarbital +
diazepam)
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The pharmacological «face» of hypnotic medicinesPhenobarbital reladorm bromisoval zolpidem = zopiclon nitrazepam
Medicines Sleep
duration
Accu-
mulati
-on
Addiction Effective in disorder of Withdra-
wal
Disorder
of the
sleep
phases
After
action
Falling
asleep
Sleep
duration
Phenobarbital 8-10 +++ +++ + + +++ + +++
Cyclobarbital 5-6 ++ +++ + +++ + ++
Nitrazepam 6-8 + ++ + + ++ + ++
Zopiderm 6-8 - + + + -
Zopiclone 6 - + + -
Bromisoval 6 ++ - + - ++
Reladorm 6 ++ +++ + + +++ ++
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Anticonvulsants
Anticonvulsant medicines decrease or stop
convulsions in pathological states of the organism
Mechanism of action
Inhibition the pathological activity of neurons in epileptic
foci of motor cortex areas and subcortical structures by
reducing the utilization of O2, energetic and exciting action
of amino acids (glutaminum and aspartamum), blocking Ca-
and Na-channels in the epileptic foci, stimulation of GABA-
ergic inhibitory mechanisms
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Classification
Benzodiazepines Valproates Barbiturates
Diazepam
Clonazepam
Valproic acid Benzobarbital
Phenobarbital
Succinimides Iminostilbens Others
Ethosuccimide Carbamazepine Tolperizone
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Pharmacodynamics (effects) → Indications
Anticonvulsant effect Convulsions of different origin
(epilepsy, craniocerebral traumas,
tumours of the CNS, meningitis)
Side effects → Contraindications
CNS inhibition, mental confusion,
drowsiness, depression, tolerance
Activities that require attention,
depression
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Effects and related indications
The principles of correct usage of anticonvulsants:
- Individually assemble the necessary combination of drugs;
- Increase the dose gradually;
- Evaluate the effectiveness of drugs in a few weeks of treatment
(number of convulsions should decrease by 50%);
- If necessary to make the gradual replacement of one drug,
reducing its dose, the second (in increasing doses);
- Conduct continuous therapy (discontinuation of the drug allowed
after 4-5 years in the absence of pathological changes in
electroencephalogram).
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Antiparkinsonian medicines
Pharmacodynamics (effects) → Indications
Antiparksionian effect Parkinsons desease, Parkinson syndrome
Side effects → Contraindications
Antiholynergic tachycardia
glaucoma, constipation
Dophaminenergic psychosis
Antiglutamatergic Epilepsy, hypotension
All medications must be taken with brief intervals
(1-2 days / week) for the prevention of tolerance (habituation).
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The pharmacological «face» of anticonvulsantsMedicines Convulsive attacks:
g\s
Epyleptic status SE Other effects
Benzobarbital +
-
- + Sedative, hypnotic
Phenobarbital +
-
+ ++
Diazepam
-
+ +++ Sedative, hypnotic,
tranquilizing
Clonazepam +
+
+ ++
Carbamazepine +
-
- +++ Antidepressant,
normothymic, analgesic
Valproic acid +
+
- + Anxiolytic
Ethosuccimide -
+
- + Tranquilizing, analgesic
Tolperizone -
+
- + Sedative, hypnotic
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Drugs used to treat Parkinson disease and syndrome of
parkinsonism, including medicinal parkinsonism.
Mechanism of action
At these diseases in the CNS is disturbed balance of neurotransmitters:
the quantity of dopamine and acetylcholine content is increased. These
means restoring the balance between dopaminergic and cholinergic brain
systems.
The mechanism of action of drugs are divided into:
I. Anticholinergic - blocking the central (reducing the influence of
acetylcholine in the CNS) and peripheral M-cholinoreceptors.
II. Dopaminergic - restore the dopamine deficiency in the CNS.
III. Antyglutamatergic - reduce the exciting action of glutamate neurons
in the CNS, which develop on the background of dopaminergic system
failure.
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Drugs for parkinsonism treatment
Classification of medicines
Anticholinergic
(cholinolytic)
Dophaminer-
gic ones
Antiglutamatergic
ones
Trihexiphenydil Levodopa
Levodopa +
carbidopa (Nacom)
Bromocriptine
Selegiline
Amantadine
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Dopaminergic ending
LevodopaLevodopa
DOPA decarboxylase
Amantadine
Bromocriptine
CNS
Amantadine
Postsinaptic D2-receptors
Selegiline
Dopamine
reuptake
Dopamine
release
Dopamine
Mechanism of action
The pharmacological «face» of antiparkinsonian medicines
Medicines Antiparkinsonian
effectSide
effects
Other effects
Levodopa +++
(gold standard
therapy)
+ The maximum effect in a month.Little impact on theautonomic and mental disorders, a characteristicphenomenon of "inclusion and exclusion"
Nacom +
(briefly)
+,
tolerance
Combination: levodopa, carbidopa. The effect is rapid,
less toxic
Selegiline ++ + Antidepressant.The need to combine with levodopa or
nakomom
Trihexilphe-
nydil
+ ++ Cholinolytic
Amantadine + +,
tolerance
Cholinolytic, antiviral
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