Norepinephrine Bitartrate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV continuous infusion	0.05-0.5 mcg/kg/min (initial 0.05-0.1 mcg/kg/min, titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Administer via central line if possible; monitor blood pressure and heart rate closely.
Cat	IV continuous infusion	0.05-0.5 mcg/kg/min (initial 0.05-0.1 mcg/kg/min, titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Cats may be sensitive; use low end of dose range initially.
Horse	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Monitor for arrhythmias; use with caution in horses with cardiac disease.
Cattle	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Not commonly used; ensure adequate fluid resuscitation first.
Small Ruminants	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Use with caution; monitor for tissue ischemia.
Rabbit	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Use central line if possible; monitor closely.
Birds/Poultry	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Limited data; use with caution.
Exotic/Other	IV continuous infusion	0.05-0.2 mcg/kg/min (titrate to effect)	Continuous infusion	Duration: As needed, titrate to blood pressure Notes: Individualize based on species and clinical response.

Clinical Indications & Species Uses

General Indications

Emergency treatment of acute hypotension
Vasopressor support in shock states

Dog (Canine)

Treatment of hypotension (e.g., septic shock, vasodilatory shock)
Adjunct to fluid therapy in hypovolemic shock
Management of anesthesia-induced hypotension

Cat (Feline)

Treatment of hypotension (e.g., septic shock, vasodilatory shock)
Adjunct to fluid therapy in hypovolemic shock

Horse (Equine)

Treatment of hypotension during anesthesia
Management of vasodilatory shock

Rabbit & Small Mammals

Treatment of hypotension during anesthesia or critical care

Pharmacology & Mechanism of Action

Drug Class: Sympathomimetic (catecholamine) | Pharmacological Group: Alpha-1 and beta-1 adrenergic agonist

Mechanism of Action: Norepinephrine is a potent alpha-1 and beta-1 adrenergic receptor agonist. It primarily acts on alpha-1 receptors in vascular smooth muscle, causing vasoconstriction and increasing systemic vascular resistance (SVR). Its beta-1 agonism increases cardiac contractility and heart rate, but the reflex bradycardia from baroreceptor activation often offsets the chronotropic effect. It has minimal beta-2 activity, so bronchodilation and vasodilation are negligible. The net effect is a rise in mean arterial pressure (MAP) with variable changes in cardiac output.

Pharmacodynamics: Norepinephrine produces dose-dependent increases in blood pressure and systemic vascular resistance. It increases myocardial oxygen demand due to increased afterload and inotropy. It reduces renal and splanchnic blood flow due to vasoconstriction, which can be beneficial in septic shock to maintain perfusion pressure but may risk organ ischemia if used excessively. It also causes venoconstriction, increasing venous return. The drug's effects are rapid in onset and short-lived due to rapid metabolism.

⚡ Pharmacokinetics Summary

Absorption: Not administered orally due to poor absorption and extensive first-pass metabolism. Administered intravenously as a continuous infusion.

Distribution: Rapidly distributes into tissues. Crosses the placenta minimally. Volume of distribution is approximately 0.15-0.2 L/kg in humans; similar in animals.

Metabolism: Rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and other tissues to inactive metabolites (normetanephrine, vanillylmandelic acid).

Excretion: Metabolites are excreted primarily in urine (85-90%) as sulfate and glucuronide conjugates, with a small fraction excreted unchanged.

Half-Life: Short half-life: approximately 1-2 minutes in dogs and cats; 2-3 minutes in horses.

Bioavailability: Not applicable (IV only).

Protein Binding: Approximately 25-30% bound to plasma proteins.

Available Formulations & Strengths

Injectable Solution (concentrate for IV infusion) 1 mg/mL (as bitartrate salt) in 4 mL ampules (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to norepinephrine or any component
Hypotension due to hypovolemia unless fluid resuscitation has been performed
Mesenteric or peripheral vascular thrombosis
Severe hypertension
Use with cyclopropane or halogenated hydrocarbon anesthetics (risk of arrhythmias)

Warnings & Clinical Precautions:

Use with extreme caution in patients with cardiac disease, arrhythmias, or hyperthyroidism
Monitor blood pressure, heart rate, ECG, and urine output continuously
Extravasation can cause tissue necrosis; administer via central line if possible
May cause renal and mesenteric ischemia; use lowest effective dose
Avoid in patients with uncorrected hypovolemia
Use with caution in geriatric or debilitated patients
In food animals, observe withdrawal times

Adverse Effects & Reactions

Common:

Hypertension
Reflex bradycardia
Arrhythmias (tachycardia, PVCs)
Anxiety, restlessness
Headache (in humans; may be inferred in animals)
Tissue ischemia at injection site if extravasation

Serious / Severe:

Tissue necrosis and sloughing (extravasation)
Cardiac arrhythmias (ventricular tachycardia, fibrillation)
Cerebral hemorrhage (severe hypertension)
Pulmonary edema (due to increased afterload)
Renal failure (prolonged vasoconstriction)

Rare:

Gangrene of extremities
Hyperglycemia
Metabolic acidosis
Hypokalemia

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Tricyclic antidepressants (e.g., amitriptyline)	Potentiate the pressor response; increased risk of arrhythmias	High
MAO inhibitors (e.g., selegiline)	Severe hypertensive crisis	High
Beta-blockers (e.g., propranolol)	Unopposed alpha-adrenergic effects leading to severe hypertension and bradycardia	High
Alpha-blockers (e.g., phenoxybenzamine)	May reverse the pressor effect, causing hypotension	Moderate
Halogenated anesthetics (e.g., halothane)	Increased risk of ventricular arrhythmias	High
Ergot alkaloids (e.g., ergotamine)	Additive vasoconstriction; risk of gangrene	High
Corticosteroids	May potentiate vasoconstrictive effects	Mild
Digoxin	Increased risk of arrhythmias	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypertension
Reflex bradycardia
Ventricular arrhythmias
Headache
Photophobia
Retrosternal pain
Pulmonary edema
Cerebral hemorrhage
Metabolic acidosis

Emergency Treatment Protocol: Discontinue infusion immediately. Administer a short-acting alpha-adrenergic blocker (e.g., phentolamine) for severe hypertension. Treat arrhythmias with appropriate antiarrhythmics (e.g., lidocaine for ventricular arrhythmias). Provide supportive care including oxygen, fluids, and monitoring. For extravasation, infiltrate the area with phentolamine (5-10 mg in 10-15 mL saline) to prevent necrosis.

Food Animal Withdrawal Times

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

Norepinephrine is a short-acting emergency drug; no withdrawal times are established. However, in food animals, use should be under veterinary supervision and follow label or extra-label regulations. Since it is used in critical situations, withdrawal times may not be practical; consult regulatory guidelines.

Storage, Handling & Regulatory Information

Storage Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

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

Handling & Special Conditions: Protect from light. Keep in original container. Do not freeze. Diluted solutions should be used within 24 hours if stored at room temperature; refrigerated solutions may be used within 48 hours.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not specifically approved for veterinary use, but can be used extra-label in animals.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship. However, due to the emergency nature and short half-life, withdrawal times are not established; use with caution and ensure no residues.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Norepinephrine is a potent vasopressor used in critical care settings to manage severe hypotension, particularly in septic shock. It is typically used after adequate fluid resuscitation. It should be administered via a central venous catheter to minimize the risk of extravasation. Continuous monitoring of blood pressure (ideally invasive), heart rate, ECG, and urine output is essential. The infusion should be titrated to achieve a target mean arterial pressure (e.g., >65 mmHg in dogs and cats). In veterinary medicine, it is used less commonly than dopamine or vasopressin, but it is valuable in cases of refractory hypotension. Due to its potent vasoconstrictive effects, it can compromise perfusion to vital organs if used excessively. Always use the lowest effective dose and wean gradually. In emergency situations, it can be life-saving, but careful patient selection and monitoring are paramount.

References & Literature

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