indication

For the symptomatic management of psychotic disorders, short term management of nonpsychotic anxiety in patients with generalized anxiety disorder, and for the control of severe nausea and vomiting of various causes.

pharmacology

Prochlorperazine is a piperazine phenothiazine related to high-potency neuroleptics such as perphenazine. It shares many of the actions and adverse effects of the antipsychotics.

mechanism of action

The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its antidopaminergic effects. Prochlorperazine blocks the D2 somatodendritic autoreceptor, resulting in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Prochlorperazine also has anti-emetic effects, which can be attributed to dopamine blockade in the chemoreceptor trigger zone. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors, the blockade of alpha(1)-adrenergic receptors resulting in sedation, muscle relaxation, and hypotension.

toxicity

Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus; LD₅₀=400mg/kg (orally in mice)

biotransformation

Hepatic. Undergoes metabolism in the gastric mucosa and on first pass through the liver, CYP2D6 and/or CYP3A4.

absorption

Rapidly absorbed following oral administration

half life

6 to 8 hours

drug interactions

Amphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Benzphetamine: Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.

Bromocriptine: The phenothiazine decreases the effect of bromocriptine

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Dexfenfluramine: Decreased anorexic effect, may increase psychotic symptoms.

Dextroamphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Diethylpropion: Decreased anorexic effect, may increase psychotic symptoms.

Donepezil: Possible antagonism of action

Fenfluramine: Decreased anorexic effect, may increase psychotic symptoms.

Galantamine: Possible antagonism of action

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanethidine: Prochlorperazine may decrease the effect of guanethidine.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Mazindol: Decreased anorexic effect, may increase psychotic symptoms.

Methamphetamine: Decreased anorexic effect, may increase pyschotic symptoms

Metrizamide: Increased risk of convulsions

Phendimetrazine: Decreased anorexic effect, may increase pyschotic symptoms

Phenmetrazine: Decreased anorexic effect, may increase pyschotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms.

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms.

Rivastigmine: Possible antagonism of action

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Prochlorperazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Trimethobenzamide: Trimethobenzamide and Prochlorperazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Prochlorperazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Prochlorperazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.