indication

For the treatment of schizophrenia and related psychotic disorders.

pharmacology

Aripiprazole is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Aripiprazole is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Aripiprazole acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Aripiprazole. Aripiprazole's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Aripiprazole's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.

mechanism of action

Aripiprazole's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.

biotransformation

Hepatic.

half life

75-146 hours

route of elimination

Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.

drug interactions

Carbamazepine: Carbamazepine, a strong CYP3A4 inducer, may decrease the serum concentration of aripiprazole by increasing its metabolism.

Dihydroquinidine barbiturate: Quinidine increases the effect and toxicity of aripiprazole

Itraconazole: Itraconazole may increase the effect of aripiprazole.

Ketoconazole: Ketoconazole may increase the effect of aripiprazole.

Quinidine: Quinidine increases the effect and toxicity of aripiprazole

Quinidine barbiturate: Quinidine increases the effect and toxicity of aripiprazole

Tacrine: Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Aripiprazole. Monitor for extrapyramidal symptoms.

Telithromycin: Telithromycin may reduce clearance of Aripiprazole. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Aripiprazole if Telithromycin is initiated, discontinued or dose changed.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Aripiprazole. Consider alternate therapy or monitor for therapeutic/adverse effects of Aripiprazole if Terbinafine is initiated, discontinued or dose changed.

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Triprolidine: The CNS depressants, Triprolidine and Aripiprazole, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of aripiprazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of aripiprazole if voriconazole is initiated, discontinued or dose changed.