Chlorpromazine
Chlorpromazine is the prototype **phenothiazine** derivative, historically used as a neuroleptic and tranquilizer in veterinary medicine, though largely supplanted by acepromazine for these purposes due to acepromazine's higher potency and shorter duration of action. Currently, it is primarily utilized for its **antiemetic properties** in small animals, particularly for managing motion sickness in cats. **Key Clinical Points:** * Effectively inhibits apomorphine-induced emesis in dogs (but not cats) and morphine-induced emesis. * Does not inhibit emesis caused by copper sulfate or digitalis glycosides. * Possesses **negligible analgesic effects**; appropriate analgesia must be provided for painful conditions. * Generally contraindicated in horses due to paradoxical excitation and ataxia. * Can cause significant vasodilation and hypotension; patients must be adequately hydrated prior to administration.
Mechanism: Chlorpromazine acts primarily as a **dopamine (D2) receptor antagonist** in the central nervous system. * **Antiemetic effect:** Blocks D2 receptors in the Chemoreceptor Trigger Zone (CRTZ) of the medulla โ inhibits emetic signaling to the vomiting center. * **Sedative effect:** Antagonizes central **histamine (H1)**, **alpha-1 adrenergic**, and **dopamine** receptors โ depresses the reticular activating system. * **Cardiovascular effect:** Peripheral **alpha-1 adrenergic blockade** โ vasodilation and potential hypotension. * Also possesses weak anticholinergic (muscarinic M1 blockade) and antiserotonergic properties.
Dosing by species
- General use ยท 0.55-4.4 mg/kg IV, 2.2-6.6 mg/kg IM ยท IV/IM ยท Once
- General use ยท 0.55-4.4 mg/kg IV, 2.2-6.6 mg/kg IM ยท IV/IM ยท Once
- General use ยท 2-3.5 mg/kg IV q5-6h ยท IV ยท q5-6h
- As an antiemetic ยท 0.5 mg/kg IV, IM or SC three to four times daily ยท IV/IM/SC ยท q6-8h
- As an antiemetic ยท 2 mg (total dose) per cat PO q12h ยท PO ยท q12h
- As a preanesthetic ยท up to 1.1 mg/kg IM 1-1.5 hours prior to surgery ยท IM ยท Once
- Premedication for cattle undergoing standing procedures ยท Up to 1 mg/kg IM ยท IM ยท Once ยท May cause regurgitation if animal undergoes general anesthesia
- Premedication ยท 1 mg/kg IM ยท IM ยท Once
- Premedication ยท 0.55-3.3 mg/kg IV; 2-4 mg/kg IM ยท IV/IM ยท Once
Routes of administration
Contraindications
- Horses (generally not recommended due to severe ataxia and panic reactions)
- Rabbits (IM injection causes severe muscle discomfort and swelling)
- Hypovolemia or shock
- Tetanus or strychnine intoxication (due to extrapyramidal effects)
Adverse effects
- Hypotension
- CNS stimulation (paradoxical)
- Bradycardia or tachycardia
- Extrapyramidal signs in cats (tremors, shivering, rigidity, loss of righting reflexes)
- Lethargy
- Diarrhea
- Loss of anal sphincter tone
- Ataxia, excitation, and panic reactions in horses
- Hypothermia or hyperthermia
Drug interactions
- Acetaminophen ยท Possible increased risk for hypothermia
- Antacids ยท May cause reduced GI absorption of oral phenothiazines
- 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
- Dipyrone ยท May cause serious hypothermia
- Epinephrine ยท Phenothiazines block alpha-adrenergic receptors; concomitant epinephrine can lead to unopposed beta-activity causing vasodilation and increased cardiac rate (epinephrine reversal)
- Opiates ยท May enhance hypotensive effects; chlorpromazine dosages may need reduction
- Organophosphate Agents ยท Effects may be potentiated; do not give phenothiazines within one month of worming with these agents
- Paraquat ยท Toxicity may be increased by chlorpromazine
- Phenytoin ยท Metabolism may be decreased if given concurrently
- Physostigmine ยท Toxicity may be enhanced by chlorpromazine
- Procaine ยท Activity may be enhanced by phenothiazines
Monitoring
- Cardiac rate, rhythm, and blood pressure (if indicated and possible)
- Degree of tranquilization and anti-emetic activity
- Body temperature (especially in extreme ambient temperatures)
Overdose
Small overdoses typically cause somnolence. Larger overdoses can cause serious effects including **coma, agitation/seizures, ECG changes/arrhythmias, hypotension, and extrapyramidal effects**. * **Treatment:** Most overdoses are managed with supportive care and monitoring. Massive oral overdoses should be treated by emptying the gut if possible. * **Hypotension Management:** Do NOT treat hypotension with epinephrine (due to epinephrine reversal). Use **phenylephrine** or **norepinephrine** (levarterenol). * **Seizure Management:** Control seizures with barbiturates or diazepam.
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.