Review of Pharmacology - 9E (2015)

Review of Pharmacology
Central Nervous System
Ziprasidone can cause QT prolongation
and Quetiapine can
cause cataract formation.
Asenapine is used sublingually.
• Trifluperazine, fluphenazine and haloperidol
v These are high potency drugs and have least α blocking, anticholinergic, sedative
and proconvulsant actions. However, extrapyramidal symptoms are marked.
• Penfluridol is the longest acting antipsychotic drug.
• Pimozide selectively blocks D 2
receptors without affecting a and muscarinic
receptors. It also possesses long duration of action. It carries the risk of arrhythmias
due to QT prolongation.
• Clozapine is an atypical antipsychotic drug having weak D 2
blocking action. It
mainly acts by blocking 5-HT 2
, a adrenergic and D 4
receptors. It suppresses both
positive as well as negative symptoms (First FDA approved drug for antisuicide indication)
of schizophrenia. It is used only as a reserve drug due to the risk of precipitation
of seizures (even in non-epileptics) and agranulocytosis. Convulsions are dosedependent
adverse effect seen only in high doses whereas agranulocytosis
is independent of dose. Because of association with myocarditis, clozapine is
contra-indicated in patients with severe heart disease. It has powerful anticholinergic
effects (equivalent to chlorpromazine and thioridazine). Risk of extrapyramidal
symptoms is least with the use of this drug. It specifically has two risks of intestinal
dysfunction; potentially severe ileus and sialorrhea.
• Risperidone: It acts by blocking 5-HT 2
, a adrenergic and D 2
receptors. It is more
potent D 2
blocker than clozapine and can cause extrapyramidal symptoms at high
dose. Risk of precipitation of seizures is less than clozapine. Hyperprolactinemia
has been reported more commonly with risperidone than other atypical
antipsychotics. Its active metabolite (paliperidone) has lesser risk of causing
metabolic adverse effects.
• Olanzapine: It has similar mode of action as risperidone. It is also a potent anticholinergic
drug and can cause dry mouth and constipation. It can cause seizures
and weight gain. Apart from its use in schizophrenia, it is also used in acute mania
and bipolar disorder. It has been associated with significantly higher risk of stroke
and death in elderly patients.
• Ziprasidone: It causes QT prolongation and carries risk of arrhythmias.Unlike
other atypical antipsychotics, it is not associated with weight gain, hyperlipidemia
or diabetes.
• Quetiapine: Can cause cataract formation. It has shortest half life.
• Aripiprazole: Acts as a partial agonist at 5-HT 1A
and D 2
receptors and antagonist
at 5-HT 2A
receptors. It is also known as dopamine- serotonin stabilizer. It has quite
long half life. It has also been approved for treatment of irritability associated with
autistic disorders in children.
• Asenapine is used sublingually for schizophrenia and acute mania.
• Iloperidone has less risk of extrapyramidal adverse effects but cause orthostatic
hypotension and can prolong QT interval.
328
Acute muscular dystonia is the
earliest appearing symptom
whereas akathisia is the most
common extrapyramidal symptom.
Adverse Effects
• Sedation (maximum with chlorpromazine; minimum with ziprasidone and
aripiprazole), weight gain (with all, less with ziprasidone) and aggravation of
seizures (more with clozapine, olanzapine and chlorpromazine; less chances with
risperidone and quetiapine).
• Postural hypotension and inhibition of ejaculation (α blocking property).
• Weight gain (with all except haloperidol). All atypical anti-psychotics may result in
weight gain, hyperlipidemia and new-onset diabetes except ziprasidone.
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