Epinephrine Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: For cardiac arrest, use low-dose IV/IO. For anaphylaxis, administer IM at 0.01 mg/kg (0.01 ml/kg of 1:1000) or IV at 0.005-0.01 mg/kg.
Cat	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: For anaphylaxis, administer IM at 0.01 mg/kg (0.01 ml/kg of 1:1000) or IV at 0.005-0.01 mg/kg.
Horse	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: For anaphylaxis, administer IM at 0.01 mg/kg (0.01 ml/kg of 1:1000) or IV at 0.005-0.01 mg/kg.
Cattle	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: For anaphylaxis, administer IM at 0.01 mg/kg (0.01 ml/kg of 1:1000) or IV at 0.005-0.01 mg/kg.
Small Ruminants (sheep, goats)	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: For anaphylaxis, administer IM at 0.01 mg/kg (0.01 ml/kg of 1:1000) or IV at 0.005-0.01 mg/kg.
Rabbit	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: Use with caution; rabbits are sensitive to catecholamines.
Birds/Poultry	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: Use with caution; birds are sensitive to catecholamines.
Exotic/Other	IV	0.01-0.02 mg/kg (10-20 mcg/kg)	Every 3-5 minutes as needed during CPR	Duration: As needed Notes: Dose may vary; use lowest effective dose.

Clinical Indications & Species Uses

General Indications

Emergency treatment of acute anaphylaxis
Cardiopulmonary resuscitation (CPR)
Adjunct to local anesthetics to reduce systemic toxicity and prolong anesthesia
Treatment of severe hypotension refractory to fluid therapy

Dog (Canine)

Cardiac arrest
Anaphylaxis
Severe hypotension
Adjunct in local anesthesia to prolong effect
Treatment of bronchospasm (less common)

Cat (Feline)

Cardiac arrest
Anaphylaxis
Severe hypotension
Adjunct in local anesthesia

Horse (Equine)

Cardiac arrest
Anaphylaxis
Severe hypotension
Adjunct in local anesthesia

Cattle (Bovine)

Cardiac arrest
Anaphylaxis
Severe hypotension
Adjunct in local anesthesia

Small Ruminants (Sheep / Goat)

Cardiac arrest
Anaphylaxis
Severe hypotension
Adjunct in local anesthesia

Rabbit & Small Mammals

Cardiac arrest
Anaphylaxis
Severe hypotension

Avian & Poultry

Cardiac arrest
Anaphylaxis
Severe hypotension

Exotic & Other Species

Cardiac arrest
Anaphylaxis
Severe hypotension

Pharmacology & Mechanism of Action

Drug Class: Sympathomimetic Agent | Pharmacological Group: Catecholamine

Mechanism of Action: Epinephrine is a direct-acting sympathomimetic that stimulates alpha- and beta-adrenergic receptors. Its effects are dose-dependent: at low doses, beta-adrenergic effects predominate (bronchodilation, increased cardiac rate and contractility, vasodilation in skeletal muscle), while at higher doses, alpha-adrenergic effects become prominent (vasoconstriction, increased peripheral resistance, increased blood pressure). It also activates beta-adrenergic receptors in the liver and muscle, promoting glycogenolysis and increasing blood glucose levels.

Pharmacodynamics: Epinephrine produces a rapid and intense sympathomimetic response. It increases heart rate, myocardial contractility, and automaticity via beta-1 receptor activation. It causes bronchodilation via beta-2 receptors. At higher doses, alpha-1 receptor activation causes vasoconstriction in cutaneous, mucosal, and renal vascular beds, while beta-2 activation causes vasodilation in skeletal muscle. It also relaxes gastrointestinal smooth muscle and dilates pupils. It stimulates the renin-angiotensin system and increases metabolic rate.

⚡ Pharmacokinetics Summary

Absorption: Epinephrine is poorly absorbed after oral administration due to rapid metabolism in the gastrointestinal tract and liver. It is well absorbed after subcutaneous or intramuscular injection, with onset of action within 5-10 minutes. Intravenous administration provides immediate effect.

Distribution: Epinephrine is widely distributed throughout the body, crossing the placenta but not the blood-brain barrier to a significant extent. It is taken up by sympathetic nerve endings and metabolized in the liver and other tissues.

Metabolism: Epinephrine is rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and other tissues. Major metabolites include metanephrine and vanillylmandelic acid (VMA).

Excretion: Metabolites are excreted primarily in the urine, with a small fraction excreted unchanged. The renal clearance is high, and the elimination half-life is very short (approximately 1-2 minutes).

Half-Life: 1-2 minutes (plasma half-life in dogs and cats)

Bioavailability: Oral bioavailability is negligible; subcutaneous or intramuscular administration provides variable but adequate absorption. Intravenous administration provides 100% bioavailability.

Protein Binding: Approximately 50% bound to plasma proteins (mainly albumin).

Available Formulations & Strengths

Injectable Solution 1 mg/mL (1:1000), 0.1 mg/mL (1:10,000) (IV, IM, SC, Intracardiac (emergency))

Auto-injector (for human use, may be used in animals) 0.3 mg/0.3 mL, 0.15 mg/0.3 mL (IM)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to epinephrine or any component
Cardiac arrhythmias (e.g., ventricular fibrillation) unless due to anaphylaxis or cardiac arrest
Coronary insufficiency
Hypertension
Hyperthyroidism
Diabetes mellitus (use with caution)
Narrow-angle glaucoma
During general anesthesia with halogenated hydrocarbons (e.g., halothane) due to risk of ventricular arrhythmias
Do not use in patients with shock (other than anaphylactic shock) or during labor (may delay second stage)

Warnings & Clinical Precautions:

Use with extreme caution in patients with cardiovascular disease, hypertension, or arrhythmias
May cause tissue necrosis if extravasation occurs; administer into a large vein and check for blood return
Use with caution in patients with hyperthyroidism, diabetes, or pheochromocytoma
May cause pulmonary edema if used in excessive doses
In food animals, observe withdrawal times; use extra-label with caution
Do not use in animals with known hypersensitivity
Use with caution in geriatric or debilitated animals
May cause anxiety, tremors, or restlessness
In horses, may cause sweating and muscle tremors
In birds, may cause severe vasoconstriction; use with caution

Adverse Effects & Reactions

Common:

Tachycardia
Pallor
Tremors
Restlessness
Anxiety
Sweating (in horses)
Piloerection

Serious / Severe:

Ventricular arrhythmias
Hypertension
Pulmonary edema
Cerebral hemorrhage
Myocardial ischemia
Tissue necrosis at injection site
Metabolic acidosis

Rare:

Angina
Cardiac arrest
Hyperglycemia
Hypokalemia
Rebound hypotension

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Beta-blockers (e.g., propranolol)	May cause unopposed alpha-adrenergic effects leading to severe hypertension and bradycardia	High
Alpha-blockers (e.g., phenoxybenzamine)	May cause unopposed beta-adrenergic effects leading to hypotension and tachycardia	Moderate
Halogenated anesthetics (e.g., halothane)	Increased risk of ventricular arrhythmias	High
Tricyclic antidepressants (e.g., amitriptyline)	Potentiation of cardiovascular effects	Moderate
MAO inhibitors (e.g., selegiline)	Prolonged and enhanced effects of epinephrine	High
Digoxin	Increased risk of arrhythmias	Moderate
Diuretics (e.g., furosemide)	May potentiate hypokalemia	Mild
Corticosteroids	May potentiate hyperglycemia	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypertension
Tachyarrhythmias
Ventricular fibrillation
Pulmonary edema
Cerebral hemorrhage
Metabolic acidosis
Hyperglycemia
Tremors
Seizures

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Discontinue epinephrine immediately. Administer a rapidly acting alpha-adrenergic blocker (e.g., phentolamine) for hypertension. For arrhythmias, administer a beta-blocker (e.g., propranolol) or lidocaine. Supportive care includes oxygen, fluids, and correction of acidosis. In severe cases, consider extracorporeal removal (not effective due to short half-life).

Food Animal Withdrawal Times

🥩 Meat: 0 days🥛 Milk: 0 days🥚 Eggs: 0 days

Epinephrine is a naturally occurring catecholamine with a very short half-life; no withdrawal times are required. However, extra-label use in food animals must follow AMDUCA guidelines and observe appropriate withdrawal periods as determined by the veterinarian.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (15-30°C) away from light. Do not freeze.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Do not use if solution is discolored or contains precipitate. Keep in tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in veterinary medicine for certain indications (e.g., as an emergency drug). Some formulations are approved for human use but may be used in animals extra-label.

Extra-Label (Off-Label) Use: Epinephrine is a prescription drug. Extra-label use in food animals is permitted under AMDUCA with veterinary oversight; however, due to its short half-life, withdrawal times are generally not required, but a veterinarian should determine appropriate withdrawal periods based on the specific situation.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Epinephrine is a critical emergency drug used for the treatment of anaphylaxis and cardiac arrest in veterinary patients. It is most effective when administered early and at appropriate doses. For anaphylaxis, intramuscular administration into the lateral thigh is preferred due to more reliable absorption. For cardiac arrest, intravenous or intraosseous administration is recommended. Doses should be based on the patient's weight and response. Careful monitoring of heart rate, blood pressure, and electrocardiogram is essential. Extravasation can cause tissue necrosis; if this occurs, infiltrate the area with phentolamine. In food animals, use with caution and follow withdrawal guidelines. Always have emergency equipment and drugs available when using epinephrine.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)