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PHARMACOLOGY OF CNS
part 1
General Pharmacology
M212
Dr. Laila M. Matalqah
Ph.D. Pharmacology
CNS drugs
 Classification:
I.

II.


Central Stimulants
Drugs which increase the activating functions of CNS
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
 Antidepressants
 Opioid analgesics: relieve pain and sleep
 Anticonvulsant: Drugs used to treat epilipsy
 Antipsychotic drugs
 Anesthetics
Neurotransmission in CNS
 A. Excitatory pathways
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
1.
Neurotransmission in CNS
B. Inhibitory pathways
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
1.
potentials
Excitatory pathways
Inhibitory pathways
1. Parkinson Disease
 Parkinsonism is a progressive neurological disorder of muscle
movement, characterized:
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 nigra
2. Increased activity of cholinergic (excitatory) fibers in the based
ganglia
1.
Drugs Used In Parkinson Disease
A. 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?

Drugs Used In Parkinson Disease
 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.
2.
3.
4.
Anorexia, nausea, and vomiting: CTZ stimulation
Tachycardia: dopaminergic action
Mydriasis: Adrenergic action
Saliva and urine are a brownish color
CNS effects:
1.
2.
3.
Visual and auditory hallucinations and abnormal
involuntary movements (dyskinesias)
Mood change
Drugs Used In Parkinson Disease
Ph/K
Drug interaction
 Levodopa has an extremely
 The vitamin pyridoxine
 short 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.
(B6) increases the
peripheral breakdown of
levodopa and diminishes its
effectiveness
Drugs Used In Parkinson Disease
B. Dopamine-receptor agonists
Bromocriptine
2. Apomorphine
3. Rotigotine
S/e : same like levodopa
1.
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. Selegiline
 MOA: inhibits MAOType B (which metabolizes dopamine)
at low to moderate doses
 S/E: insomnia
E.

Amantadine
antiviral drug in the treatment of influenza
 MOA: increase the release of dopamine, blocking
cholinergic receptors
 The drug has little effect on tremor, but it is more effective
than the anticholinergics against rigidity and bradykinesia
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 Drugs
Benzodiazepines
II. Barbiturates
III. Others: Chloral Hydrate
I.
Benzodiazepines
 MOA:
 Activate (GABAA ) receptors (inhibitory NT)
 Binding of GABA to its receptor triggers an open ing of a chloride channel
 Therapeutic Actions
1.
2.
3.
4.
Reduction of anxiety: at low doses, the benzodiazepines are anxiolytic
(α2-GABA) E.g., clonazepam , lorazepam and diazepam
Sedative and hypnotic actions at higher doses. (α1-GABA) Temazepam
and Flurazepam
Anticonvulsant: to treat epilepsy e.g., , lorazepam and diazepam (α1GABA)
Muscle relaxant: At high doses: e.x: Diazepam for multiple sclerosis
Benzodiazepines
 Long-acting:
 Clonazepam
 Diazepam
 Flurazepam
 Intermediate acting:
 Alprazolam
 Lorazepam
 Temazepam
 Short-acting:
 Oxazepam
 Triazolam
Benzodiazepines
Adverse effect
1. Drowsiness and confusion
2. 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. Hypnotic and anxiolytics Drugs
Barbiturates
 MOA: Bind GABAA receptors, which enhances GABAergic
transmission
 Therapeutic Actions
1. Anticonvulsant: Phenobarbital is used in long-term
management of seizures
2. Anesthesia: thiopental, are used intravenously to induce
2.
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
Barbiturates
Pharmacokinetics:
 Enzyme induction: Barbiturates induce CYP450 in the
liver.

 Side effects:
1.
2.
3.
4.
5.
CNS: Drowsiness
Drug hangover
Addiction
Respiratory depression
Physical dependence: Withdrawal symptoms: tremor,
seizures, cardiac arrest….
2. Hypnotic and anxiolytics Drugs
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
Alcohol
• Drugs to treat alcohol dependence
1. Disulfiram: blocks the oxidation of acetaldehyde to acetic
3.
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