THERAPEUTICS

Brands

• Thorazine, Largactil, Sonazine, Promapar

Generic?

• Yes

Class

• Antiemetic, antipsychotic

Commonly Prescribed for

(FDA approved in bold)

• Antiemetic

• Intractable hiccups

• Psychosis, schizophrenia

• Manic depression in bipolar disorder

• Acute intermittent porphyria

• Adjunct treatment for tetanus

• Restlessness and apprehension before surgery

• Hyperactivity and behavioral problems (children)

• Acute treatment for migraine

How the Drug Works

• It is an aliphatic phenothiazine derivative with high antagonistic effect for α1-adrenergic, H1, M1, and 5-HT2 receptors, but low affinity for D1–4 receptors; hence it has high risk for sedation, weight gain, and orthostatic hypotension but lower risk for dyskinesia than haloperidol

How Long Until It Works

• Migraine: 1 hour (oral) or less than 30 minutes (IV)

If It Works

• Use at lowest required dose

• Monitor QTc interval

If It Doesn't Work

• Change to another agent

Best Augmenting Combos for Partial Response or Treatment-Resistance

• For migraine, can be used with dihydroergotamine or NSAIDs

Tests

• Obtain blood pressure and pulse before initial IV and monitor QTc with ECG

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Anticholinergic effects produce most AEs (sedation, blurred vision, dry mouth). Hypotension and dizziness are related to α-adrenergic blockade, and motor AEs are related to dopamine blocking effects

Notable AEs

• Dizziness, sedation, orthostatic hypotension, tachycardia, urinary retention, depression

• Akathisia, extrapyramidal symptoms, parkinsonism

• Long-term use: weight gain, glucose intolerance, sexual dysfunction, hyperprolactinemia

Life-Threatening or Dangerous AEs

• Tardive dyskinesias

• Neuroleptic malignant syndrome (rare)

• Jaundice

• Rare agranulocytosis (mean exposure of 45 days to onset; mean duration of 11 days)

Weight Gain

• Common (with chronic use)

Sedation

• Problematic

What to Do About AEs

• Lowering dose or changing to another antiemetic improves most AEs

• Rarely causes ECG changes. Use with caution in patients if QTc is above 450 (females) or 440 (males) and do not administer with QTc greater than 500