Lisinopril — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-1 mg/kg	q24h	Duration: Long-term; adjust based on response Notes: Start at lower end, titrate up to effect. Monitor blood pressure and renal function.
Cat	PO	0.25-0.5 mg/kg	q24h	Duration: Long-term; adjust based on response Notes: Cats are sensitive to ACE inhibitors; start low and monitor renal function.
Horse	PO	0.5-1 mg/kg	q12-24h	Duration: As needed Notes: Limited data; use with caution.
Rabbit	PO	0.5-1 mg/kg	q24h	Duration: As needed Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Hypertension
Congestive heart failure
Proteinuria in chronic kidney disease

Dog (Canine)

Heart failure (congestive heart failure) due to mitral regurgitation or dilated cardiomyopathy
Systemic hypertension
Protein-losing nephropathy (to reduce proteinuria)

Cat (Feline)

Heart failure (congestive heart failure) due to hypertrophic cardiomyopathy or other causes
Systemic hypertension
Chronic kidney disease with proteinuria

Pharmacology & Mechanism of Action

Drug Class: Angiotensin-Converting Enzyme (ACE) Inhibitor | Pharmacological Group: Cardiovascular Agent

Mechanism of Action: Lisinopril is a competitive inhibitor of angiotensin-converting enzyme (ACE), which catalyzes the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. By inhibiting ACE, lisinopril reduces angiotensin II levels, leading to vasodilation, decreased aldosterone secretion, and reduced sodium and water retention. It also increases bradykinin levels, contributing to vasodilatory effects. These actions result in decreased systemic vascular resistance, reduced blood pressure, and decreased cardiac workload. In heart failure, lisinopril improves cardiac output and reduces preload and afterload.

Pharmacodynamics: Lisinopril produces a dose-dependent reduction in blood pressure in hypertensive animals. It reduces systemic vascular resistance without causing reflex tachycardia. In heart failure, it improves hemodynamic parameters such as cardiac output, stroke volume, and pulmonary capillary wedge pressure. It also reduces proteinuria in chronic kidney disease by decreasing intraglomerular pressure and preserving renal function. The onset of action is within 1-2 hours, with peak effects at 4-6 hours, and duration of action is approximately 24 hours.

⚡ Pharmacokinetics Summary

Absorption: Lisinopril is poorly absorbed after oral administration, with an oral bioavailability of approximately 25-30% in dogs and cats. Absorption is not affected by food. Peak plasma concentrations occur within 6-8 hours.

Distribution: Lisinopril is widely distributed, with a volume of distribution of approximately 0.15-0.3 L/kg. It does not cross the blood-brain barrier significantly. It crosses the placenta and is excreted in milk.

Metabolism: Lisinopril is not metabolized significantly; it is a prodrug that is already active. It does not undergo hepatic metabolism.

Excretion: Lisinopril is excreted unchanged primarily by the kidneys via glomerular filtration and tubular secretion. In animals with renal impairment, elimination is prolonged, and dose adjustment is necessary.

Half-Life: Dogs: approximately 4-6 hours; Cats: approximately 2-4 hours; Horses: approximately 1-2 hours.

Bioavailability: Oral bioavailability is approximately 25-30% in dogs and cats, but may be lower in other species.

Protein Binding: Lisinopril has minimal protein binding, approximately 10%.

Available Formulations & Strengths

Oral Tablet 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to lisinopril or other ACE inhibitors
History of angioedema
Concurrent use with aliskiren (in humans; not relevant in animals)
Severe renal impairment (unless used for renal protective effects with careful monitoring)
Pregnancy (especially in the second and third trimester) due to risk of fetal toxicity

Warnings & Clinical Precautions:

Use with caution in animals with renal insufficiency; monitor renal function and potassium levels.
May cause hypotension, especially in volume-depleted animals; ensure adequate hydration.
Use with caution in animals with aortic stenosis or other outflow obstructions.
In animals with heart failure, monitor for worsening renal function and hyperkalemia.
Do not use in pregnant animals unless the benefits outweigh risks.
May cause cough in some animals (rare).

Adverse Effects & Reactions

Common:

Hypotension
Azotemia (increased BUN/creatinine)
Hyperkalemia
Gastrointestinal upset (vomiting, diarrhea)
Lethargy

Serious / Severe:

Acute renal failure
Angioedema
Severe hypotension
Hyperkalemia-induced arrhythmias

Rare:

Cough
Hepatotoxicity
Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Potassium-sparing diuretics (e.g., spironolactone, triamterene)	Increased risk of hyperkalemia	High
Nonsteroidal anti-inflammatory drugs (NSAIDs)	Reduced antihypertensive effect and increased risk of renal dysfunction	Moderate
Diuretics (e.g., furosemide)	Additive hypotension and risk of renal impairment	Moderate
Other antihypertensives (e.g., amlodipine, beta-blockers)	Additive hypotensive effects	Moderate
Potassium supplements	Increased risk of hyperkalemia	High

Overdose & Toxicity Management

Signs of Toxicity:

Severe hypotension
Renal failure
Hyperkalemia
Bradycardia
Lethargy
Collapse

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion. Administer activated charcoal to reduce absorption. Provide intravenous fluids to maintain blood pressure and renal perfusion. Monitor serum electrolytes, especially potassium. In severe cases, administer angiotensin II (if available) or vasopressors such as norepinephrine. Treat hyperkalemia with calcium gluconate, insulin/glucose, or sodium bicarbonate. Dialysis may be considered in severe cases.

Food Animal Withdrawal Times

Not approved for use in food animals; no withdrawal times established. Use in food animals is prohibited.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C)

Handling & Special Conditions: Protect from moisture; keep in tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, lisinopril is not FDA-approved for veterinary use; it is used extra-label under AMDUCA. For food animals, extra-label use is prohibited if it results in violative residues.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Lisinopril is a commonly used ACE inhibitor in veterinary medicine, particularly for the management of heart failure and hypertension in dogs and cats. It is often preferred over enalapril due to its longer duration of action and once-daily dosing. However, it is not approved for veterinary use, so it is used extra-label. Monitoring of blood pressure, renal function (BUN, creatinine), and serum potassium is essential, especially during the first weeks of therapy. In animals with chronic kidney disease, lisinopril can be beneficial in reducing proteinuria, but dose adjustment may be necessary. It is important to start with a low dose and titrate gradually to minimize adverse effects. In cats, caution is advised due to their sensitivity to ACE inhibitors. Always consider potential drug interactions, especially with diuretics and NSAIDs. For food animals, lisinopril is not recommended due to lack of withdrawal data.

References & Literature

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