Clozapine

Question 1

Indication

Answer 1

-Treat severe schizophrenia unresponsive to standard drugs
-Reduce the risk of recurrent suicidal behavior in schizoaffective disorders

Question 2

Mechanism of Action

Answer 2

Production of antipsychotic effects by interference with dopamine binding to dopamine receptors in limbic region of the brain

Question 3

Contraindication

Answer 3

-Hypersensitivity
-Avoid alcohol
-Avoid smoking
-Avoid caffeine
-ANC <1500/mm3

Question 4

Interactions

Answer 4

Adverse reactions with select antidepressants, ClassIA&III, and antiarrhythmics increase reactions
Carbamazepine, phenytoin, and rifampin decrease the plasma level of clozapine

Question 5

Side Effects

Answer 5

CNS: akinesia, ataxia, confusion, delirium, insomnia, paresthesia, cataplexy, TD, (see p 253)

CV: palpitations, hypercholesterolemia, hypertriglyceridemia, HTN

EENT: blurred vision, dry mouth, glaucoma

GI: abdominal discomfort, anorexia, cholestasis, colitis, N/V

GU: ejaculatory disorders, priapism, urinary retention

HEME: elevated hemoglobin, hematocrit, and erythrocyte rate
MS: myalgia

RESP: lower resp tract infection

SKIN: photosensitivity

Other: hyperuricemia, weight gain

Question 6

Life-threatening SE

Answer 6

CNS: neuroleptic malignant syndrome, seizures, sleep apnea, status epilepticus

CV: atrial or ventricular fibrillation, cardiac arrest, cardiomyopathy, DVT, MI, Torsades de pointes

ENDO: DKA

GI: acute pancreatitis, hepatic cirrhosis, liver failure

GU: renal failure

HEME: agranulocytosis, bone marrow suppression,

MS: Rabdo

RESP: aspiration, PE, respiratory arrest

SKIN: erythema multiforme, Stevens-Johnson syndrome

Other: angioedema, hypersensitivity reactions, hyponatremia, sepsis