Drug Profile

1. King Saud University
College of Pharmacy
Department of
Pharmacology

2. What is Schizophrenia?
 Mental 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: Atypical (2nd 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
10 100
Therapeutic Dose (mg)
Dosage Forms Oral and IM Tablets, Injection, Oral
solution and
suppositories.

17. Conclusion
 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