Prochlorperazine
Prochlorperazine is a potent **phenothiazine antiemetic** used in veterinary medicine primarily to control severe nausea and vomiting in dogs and cats. Historically, it was widely used in veterinary-specific combination products (such as Darbazineยฎ, which included an anticholinergic), but it is now utilized off-label via human formulations. **Clinical Pearl:** Because of its broad receptor antagonism, prochlorperazine is highly effective for centrally mediated vomiting. However, due to its potential to cause significant sedation and alpha-adrenergic blockade (leading to hypotension), it is generally reserved for cases where newer, more targeted antiemetics (like maropitant or ondansetron) are ineffective or unavailable. It also possesses mild sedative and weak anticholinergic properties.
Mechanism: Prochlorperazine exerts its antiemetic effects primarily by acting on the brain's emetic center and the **Chemoreceptor Trigger Zone (CRTZ)**. Its broad-spectrum efficacy is due to the antagonism of multiple receptor types: * **Dopaminergic (D2) Antagonism** โ Blocks dopamine signaling in the CRTZ, providing the primary antiemetic effect. * **Histaminergic (H1) & Cholinergic (M1) Antagonism** โ Contributes to anti-motion sickness efficacy and mild antispasmodic effects in the GI tract. * **Alpha-1 Adrenergic Antagonism** โ Causes peripheral vasodilation, which is responsible for the primary adverse effect of hypotension. It also has strong extrapyramidal effects due to central dopamine blockade in the basal ganglia.
Dosing by species
- As an antiemetic ยท 0.5 mg/kg ยท SC or IM ยท three times a day ยท Ensure adequate hydration
- As an antiemetic ยท 0.5 mg/kg ยท IM or SC ยท q8h
- As an antiemetic ยท 0.1-0.5 mg/kg ยท IM or SC ยท q6-8h
- All uses (motion sickness, emesis) ยท 0.1-0.5 mg/kg ยท IV/IM/SC ยท q6-8h
- All uses (motion sickness, emesis) ยท 0.5-1 mg/kg ยท PO ยท q8-12h
- As an antiemetic ยท 0.5 mg/kg ยท IM or SC ยท q8h ยท Ensure adequate hydration
- As an antiemetic ยท 0.1 mg/kg ยท IM ยท q6-8h ยท Use with extreme caution in dehydrated or hypotensive animals
- As an antiemetic ยท 0.1-0.5 mg/kg ยท IM or SC ยท q6-8h
- All uses (motion sickness, emesis) ยท 0.1-0.5 mg/kg ยท IV/IM/SC ยท q6-8h
- All uses (motion sickness, emesis) ยท 0.5-1 mg/kg ยท PO ยท q8-12h
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypovolemia or dehydration
- Shock
- Tetanus
- Strychnine intoxication
- Hepatic dysfunction (use with caution)
- Cardiac disease (use with caution)
Adverse effects
- Sedation
- Hypotension
- Muscle fasciculations and tremors (extrapyramidal signs)
- Prolactin release
- Depression
- Extrapyramidal reactions (rigidity, tremors, weakness, restlessness)
Drug interactions
- Antacids ยท May cause reduced GI absorption of oral phenothiazines ยท moderate
- Antidiarrheal mixtures (e.g., Kaolin/pectin, bismuth subsalicylate) ยท May cause reduced GI absorption of oral phenothiazines
- CNS Depressant Agents (barbiturates, narcotics, anesthetics) ยท May cause additive CNS depression if used with phenothiazines
- Dopamine ยท Phenothiazines may decrease pressor effects
- Epinephrine ยท Phenothiazines block alpha-adrenergic receptors; concomitant epinephrine can lead to unopposed beta-activity causing vasodilation and increased cardiac rate (epinephrine reversal)
- Metoclopramide ยท Phenothiazines may potentiate the extrapyramidal effects of metoclopramide
- Opiates ยท May enhance the hypotensive effects of the phenothiazines; dosages of prochlorperazine may need to be reduced
- Organophosphate Agents ยท Phenothiazines should not be given within one month of worming with these agents as their effects may be potentiated
- Paraquat ยท Toxicity of the herbicide paraquat may be increased by prochlorperazine
- Phenytoin ยท Metabolism may be decreased if given concurrently with phenothiazines
- Physostigmine ยท Toxicity may be enhanced by prochlorperazine
- Procaine ยท Activity may be enhanced by phenothiazines
Monitoring
- Cardiac rate, rhythm, and blood pressure (if indicated and possible to measure)
- Anti-emetic/anti-spasmodic efficacy
- Hydration and electrolyte status
- Body temperature (especially if ambient temperature is very hot or cold)
- Heart rate and rhythm
- Blood pressure
- CNS status (sedation level, extrapyramidal signs)
- Liver function (with prolonged use)
Overdose
Overdose generally presents as an exaggeration of adverse effects, particularly profound sedation, hypotension, and **extrapyramidal clinical signs** (such as torticollis, severe tremors, muscle rigidity, and excessive salivation). > **Treatment:** Acute extrapyramidal signs have been successfully treated with injectable **diphenhydramine** in humans. Hypotension should be treated with intravenous fluids; avoid epinephrine due to the risk of "epinephrine reversal" causing further vasodilation.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.