Drug Profile: Aripiprazole

Drug Profile

1. Aripiprazole Prepared By: Sarah Abu El-Asrar Supervised By: Dr. Hazzar Yacoub & Dr. Haya Al- Rajeh King Saud University College of Pharmacy Department of Pharmacology

2. What is Schizophrenia? M ental disorder. Patients have difficulties in: Telling the difference between what is real and what isn't. Thinking clearly. Having normal emotional responses. Acting normally in social situations.

3. What causes Schizophrenia? Dopamine Theory Glutamate Theory Serotonin Theory

4. Symptoms of Schizophrenia Positive Symptoms: Delusions Hallucination (Usually in the form of voices) Thought Disorder . Abnormal behaviors, such as: stereotyped movements and occasionally aggressive behaviors.

5. Symptoms of Schizophrenia Continued Negative Symptoms: Withdrawal from social contacts. Flattening of emotional responses.

6. Treatment of Schizophrenia Chlorpromazine (A first generation/ typical antipsychotic.) Aripiprazole (A second generation/atypical antipsychotic.)

7. Aripiprazole Therapeutic Class: A typical (2 nd Generation) antipsychotic drug. MOA: It is a dopamine D2 receptor partial agonist. Partial agonist activity at serotonin 5HT1A receptors. Antagonist activity at 5HT2A receptors. It has alpha blocking activity.

8. MOA

9. Uses of Aripiprazole: Schizophrenia Bipolar Mania Depression Control of agitation and disturbed behavior

10. Side Effects Weight Gain. Postural Hypotension Extrapyramidal Symptoms Tardive dyskinesia on long-term administration Lightheadedness and drowsiness Hyperglycemia and sometimes diabetes. Increased risk of hyperlipidemia.

11. Cautions Hepatic Impairment because Aripiprazole is metabolized by hepatic enzymes (CYP3A4 and CYP2D6). Elderly patients with dementia related psychosis. Pregnancy because Aripiprazole is Category C . Patients with cardiovascular Disease. Patients predisposed to hypotension.

12. Contraindications Hypersensitivity to Aripiprazole has been documented. Therefore avoid in patients with hypersensitivity. Operating Heavy Machinery and work that requires skill (eg. driving) probably because Aripiprazole causes sedation. In breast-feeding. Aripiprazole is secreted in breast milk.

13. Pharmacokinetics Plasma Half- life: Parent Drug, 75 hr.; metabolite, 94 hr. Plasma Peak Time: 3-5 hours . Protein Bound: 99%. Absorption: Oral (3-5 hr.); IM (1-3 hr.) . Metabolism: Aripiprazole is metabolized largely by hepatic CYP2D6 and CYP3A4. Excretion: Feces (55%) and Urine. (25%) Dosage Form: Oral or IM.

14. Drug Interactions Drug Cause Reason Ritonavir Increased concentration of Aripiprazole. Ritonavir is a CYP3A4 (involved in the metabolism of Aripiprazole) inhibitor. Serotonin Reuptake Inhibitors (fluoxetine, sertraline, fluvoxamine) Increased concentration of Aripiprazole. Serotonin reuptake inhibitors are CYP2D6 (involved in the metabolism of Aripiprazole) inhibitors. Carbinoxamine Sedation Carbinoxamine and Aripiprazole both cause sedation. Additive Effect.

15. Comparison Points of Comparison Aripiprazole Chlorpromazine Therapeutic Class 2nd Generation antipsychotic 1st generation antipsychotic Chemical Class Dihydrocarbostyril Phenothiazine Mechanism of Action -D2 receptor partial agonist. -Partial agonist activity at serotonin 5HT1A receptors. -Antagonist activity at 5HT2A receptors. -D2 receptor antagonist. -5-HT2A-receptor antagonist. EPS Mild and transient and respond to dose reduction. Pronounced. T1/2 75 hr 30 hr

16. Comparison Continued Points of Comparison Aripiprazole Chlorpromazine Protein Bound 99% 92-97% Minimum Effective Therapeutic Dose (mg) 10 100 Dosage Forms Oral and IM Tablets, Injection, Oral solution and suppositories.

17. C onclusion Aripiprazole is a second-generation (atypical) antipsychotic drug used in the treatment of various mental conditions such as: schizophrenia, mania, and control of agitation and disturbed behavior. In my opinion, it is better than other antipsychotic drugs such as chlorpromazine as it has mild extrapyramidal side effects due to its unique D2 PA activity.

18. Thank you