Ozapez Mechanism of Action

Pharmacotherapeutic group: Antipsychotic. ATC Code: N05AH03.
Pharmacology: Pharmacodynamics: Olanzapine is an atypical or second-generation antipsychotic that is a thienobenzodiazepine-derivative antipsychotic agent.
Mechanism of Action: Olanzapine is an antipsychotic which displays potent antagonism of serotonin 5-HT_2A and 5-HT_2c, dopamine D_1-4, histamine H₁, and alpha₁-adrenergic receptors.
Olanzapine shows moderate antagonism of 5-HT₃ and muscarinic M_1-5 receptors, and weak binding to GABA-A, benzodiazepines, and beta-adrenergic receptors.
Although the precise mechanism of action in schizophrenia and bipolar disorder is not known, the efficacy of olanzapine is thought to be mediated through combined antagonism of dopamine and serotonin type 2 receptor sites.
Pharmacokinetics: Onset of Action: Within 1-2 weeks for control of aggression, agitation, insomnia; 3-6 weeks for control of mania and positive psychotic symptoms. Adequate trial: Typically, 6 weeks at maximum tolerated doses.
Absorption: Olanzapine is well absorbed following oral administration. Olanzapine concentrations occurred peak plasma in approximately 6 hours (range: 5-8 hours) and achieved to steady state after approximately 7 days of continuous dosing and are approximately twice those observed following single-dose administration. Food does not appear to affect GI absorption of Olanzapine.
Distribution: The apparent volume of distribution of the drug averaged 1150 L and ranged from 660 to 1790 L for the 5^th to 95^th percentiles.
Olanzapine is 93% bound to plasma proteins over the concentration range of 7-1100 ng/mL, principally to albumin and α₁-acid glycoprotein.
Olanzapine and its glucuronide metabolite have been shown to cross the placenta in humans.
Olanzapine is distributed into milk.
Metabolism: Highly metabolized via direct glucuronidation and cytochrome P450 mediated oxidation (CYP1A2, CYP2D6); 40% removed via first pass metabolism.
Elimination: Olanzapine, 7% of the dose was recovered in urine as unchanged drug. Approximately 57% and 30% of the dose was recovered in the urine and feces, respectively. After multiple dose of Olanzapine, the principal circulating metabolites are the 10-N-glucuronide, which is present at steady state at 44% of the plasma concentration of the parent drug, and 4'-N-Desmethyl Olanzapine, which is present at steady state at 31% of the plasma concentration of Olanzapine.
The apparent plasma clearance of Olanzapine ranges from 12-47 L/hour (mean: 25 L/hour).
The clearance of Olanzapine in smokers is approximately 40% higher than in non-smokers.
The clearance of Olanzapine in females may be reduced by approximately 30% compared with males.
The elimination half-life of orally administered Olanzapine was 1.5 times longer in healthy geriatric individuals 65 years of age or older than in healthy younger adults.
Olanzapine is not appreciably removed by hemodialysis, probably due to its large volume of distribution and extensive protein binding.