dr. laila m. matalqah ph.d. pharmacology pharmacology of cns part 1 general pharmacology m212

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Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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CNS pharmacology Neurodegenerative disorders : Parkinson disease Alzheimer disease Anxiolytics and hypnotics: Drugs that induce sleep Antidepressants Opioid analgesics: relieve pain and sleep Anticonvulsant: Drugs used to treat epilipsy Antipsychotic drugs Anesthetics

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Page 1: 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

Page 2: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 3: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 4: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 5: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 6: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

Excitatory pathways Inhibitory pathways

Page 7: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 8: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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?

Page 9: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212
Page 10: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 11: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 12: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 13: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 14: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 15: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 16: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 17: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

BenzodiazepinesLong-acting:

ClonazepamDiazepam Flurazepam

Intermediate acting: AlprazolamLorazepamTemazepam

Short-acting: Oxazepam Triazolam

Page 18: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 19: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 20: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 21: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212
Page 22: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 23: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212

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

Page 24: Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS part 1 General Pharmacology M212