Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212.
-
Upload
morris-bartholomew-warner -
Category
Documents
-
view
320 -
download
2
description
Transcript of Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212.
Dr. Laila M. MatalqahPh.D. Pharmacology
PHARMACOLOGY OF CNS part 1
General PharmacologyM212
CNS drugsClassification:I. Central Stimulants Drugs which increase the activating
functions of CNS
II.Central Depressants Drugs that decrease the activation of
CNS Most commonly use in therapy
CNS pharmacology Neurodegenerative disorders :
Parkinson disease Alzheimer disease
Anxiolytics and hypnotics: Drugs that induce sleep
AntidepressantsOpioid analgesics: relieve pain and sleepAnticonvulsant: Drugs used to treat epilipsy Antipsychotic drugs Anesthetics
A. Excitatory pathways1.Stimulation of an excitatory neuron causes the
release of neurotransmitter molecules, such as glutamate or acetylcholine,
2.The influx of Na+ causes a weak depolarization effect
3. If the number of stimulated excitatory neurons increases, more excitatory neurotransmitter is released
Neurotransmission in CNS
Neurotransmission in CNSB. Inhibitory pathways1.Stimulation of inhibitory neurons releases
neurotransmitter molecules, such as γ-aminobutyric acid (GABA), glycine or dopamine
2.The influx of Cl– and efflux of K+ cause a weak hyperpolarization. This diminishes the generation of action potentials
Excitatory pathways Inhibitory pathways
1. Parkinson DiseaseParkinsonism is a progressive neurological
disorder of muscle movement, characterized: 1. Tremors, 2. Muscular rigidity, 3. Bradykinesia (slowness in initiating and carrying
out voluntary movements)4. postural abnormalities.
Etiology:1.Reduction of activity of dopaminergic (inhibitory
pathway in the based ganglia and substania nigra2. Increased activity of cholinergic (excitatory) fibers
in the based ganglia
Drugs Used In Parkinson DiseaseA. Increase dopaminergic activity:Levodopa and carbidopa Levodopa is a metabolic precursor of dopamine Dopamine itself does not cross the blood-brain
barrier, but levodopa, is actively transported into the CNS and is converted to dopamine in the brain
Levodopa is decarboxylated to dopamine in the periphery, resulting in side effects that include nausea, vomiting, cardiac arrhythmias, and hypotension. So?
Carbidopa: Carbidopa, a dopa decarboxylase inhibitor
Inhibit the metabolism of levodopa in the GIT and peripheral tissues
increasing the availability of levodopa to the CNS decrease the dose of levodopa needed by 4-5
times decreases side effects.
Actions: levodopa–carbidopa (Sinemet®) decreases the rigidity, tremors, and other symptoms of parkinsonism
Drugs Used In Parkinson Disease
Adverse effects:Peripheral effects:1.Anorexia, nausea, and vomiting: CTZ stimulation2.Tachycardia: dopaminergic action3.Mydriasis: Adrenergic action4.Saliva and urine are a brownish color
CNS effects: 1.Visual and auditory hallucinations and abnormal2.involuntary movements (dyskinesias)3.Mood change
Drugs Used In Parkinson Disease
Ph/K Drug interactionLevodopa has an
extremelyshort half-life (1 to 2
hours)levodopa should be
taken on an empty stomach, typically 45 minutes before a meal.
Withdrawal from the drug must be gradual.
The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness
Drugs Used In Parkinson Disease
B. Dopamine-receptor agonists1. Bromocriptine2. Apomorphine 3. RotigotineS/e : same like levodopa
C. Anticholinergic agents Benztropine and Benzhexol an adjuvant role in antiparkinsonism therapy. S/e: pupillary dilation, confusion, sinus
tachycardia, urinary retention, constipation, and dry mouth
Drugs Used In Parkinson Disease
D. SelegilineMOA: inhibits MAO Type B (which metabolizes
dopamine) at low to moderate dosesS/E: insomnia
E.Amantadineantiviral drug in the treatment of influenzaMOA: increase the release of dopamine,
blocking cholinergic receptorsThe drug has little effect on tremor, but it is more
effective than the anticholinergics against rigidity and bradykinesia
Drugs Used In Parkinson Disease
2. Anxiolytics and Hypnotic Drugs
Anxiety: is a state of tension, apprehension, or uneasiness (a fear that seems to arise from a unknown source).
The physical symptoms of severe anxiety are similar to those of fear (such as tachycardia, sweating, trembling, and palpitations) and involve sympathetic activation.
Anxiolytics DrugsI. BenzodiazepinesII.BarbituratesIII.Others: Chloral Hydrate
BenzodiazepinesMOA:
Activate (GABAA ) receptors (inhibitory NT)Binding of GABA to its receptor triggers an open ing of a
chloride channelTherapeutic Actions1. Reduction of anxiety: at low doses, the benzodiazepines are
anxiolytic (α2-GABA) E.g., clonazepam , lorazepam and diazepam
2. Sedative and hypnotic actions at higher doses. (α1-GABA) Temazepam and Flurazepam
3. Anticonvulsant: to treat epilepsy e.g., , lorazepam and diazepam (α1-GABA)
4. Muscle relaxant: At high doses: e.x: Diazepam for multiple sclerosis
BenzodiazepinesLong-acting:
ClonazepamDiazepam Flurazepam
Intermediate acting: AlprazolamLorazepamTemazepam
Short-acting: Oxazepam Triazolam
BenzodiazepinesAdverse effect1. Drowsiness and confusion2. Psychological and physical dependence on
benzodiazepines can develop if high doses of the drugs are given over a prolonged period
3. Abrupt discontinuation of the benzodiazepines results in withdrawal symptoms, including confusion, anxiety, agitation, restlessness, insomnia.
Overdoses toxicity: Flumazenil is a GABA-receptor antagonist that can rapidly reverse the effects of benzodiazepines
2. Barbiturates MOA: Bind GABAA receptors, which enhances
GABAergic transmission Therapeutic Actions1. Anticonvulsant: Phenobarbital is used in long-
term management of seizures2. Anesthesia: thiopental, are used intravenously to
induce anesthesia. which acts within seconds and has a duration of action of about 30 minutes, is used in the
3. sedative and hypnotic: Pentobarbital, secobarbital and amobarbital are short-acting barbiturates, suppress REM sleep
2. Hypnotic and anxiolytics Drugs
Pharmacokinetics: Enzyme induction: Barbiturates induce
CYP450 in the liver.
Side effects:1. CNS: Drowsiness2. Drug hangover3. Addiction4. Respiratory depression5. Physical dependence: Withdrawal
symptoms: tremor, seizures, cardiac arrest….
Barbiturates
3. Alcohol Ethanol is an important drug of dependence Acute effect:
CNS: decrease learning ability and attention GIT: diluted- stimulate gastric secretion. Conc-
decrease gastric secretion CVS: increase HR and CO Metabolism: Hypoglycemia and metabolic acidosis
• Chronic effect: GIT: cirrhosis of liver, gastritis CNS: acohol withdrwal Myopathy
2. Hypnotic and anxiolytics Drugs
3. Alcohol• Drugs to treat alcohol dependence1. Disulfiram: blocks the oxidation of
acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase (accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea)
2. Naltrexone is better tolerated than disulfi ram
2. Hypnotic and anxiolytics Drugs