drug profile: aripiprazole

King Saud UniversityCollege of PharmacyDepartment of Pharmacology

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.

What causes Schizophrenia?

Dopamine Theory

Glutamate Theory

Serotonin Theory

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.

Symptoms of

Schizophrenia Continued

Negative Symptoms:

Withdrawal from social contacts.

Flattening of emotional responses.

Treatment of

Schizophrenia

Chlorpromazine (A first generation/ typical

antipsychotic.)

Aripiprazole (A second generation/atypical

antipsychotic.)

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.

MOA

Uses of Aripiprazole:

Schizophrenia

Bipolar Mania

Depression

Control of agitation and disturbed behavior

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.

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.

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.

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.

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.

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

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.

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.

Thank you