Toxicoses in Animals From Cardiovascular Medications

Several human angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril, captopril, lisinopril, benazepril, perindopril, quinapril) are used to treat mitral valve insufficiency, congestive heart failure, and protein-losing nephropathy in dogs and cats. ACE inhibitors have a reasonable margin of safety in dogs and cats. Specific toxic doses vary with each ACE inhibitor; in general, however, ingestions > 20 mg/kg are of concern.

The primary clinical sign of acute ACE inhibitor toxicosis is typically hypotension with reflex tachycardia. Also possible are acute renal failure and hyperkalemia, but these effects are rare. Hypotension can occur within a few hours after exposure, depending on the agent (extended-release formulations might have a delayed onset of action), and might persist for 12–24 hours. Longer durations are possible for extended-release formulations. Other clinical signs of toxicosis include vomiting, poor mucous membrane color, and weakness.

Activated charcoal is effective in binding the drug from the GI tract, if administered within 1–2 hours after ingestion, or up to 4–6 hours after ingestion of extended-release formulations. Blood pressure should be monitored and IV fluids administered if hypotension develops. Renal function should be monitored for 1–2 days if severe or persistent hypotension develops.

Electrolytes should be monitored for the duration of a hospital stay in clinically affected patients. In general, patients should be monitored for 8–10 hours after exposure, or for up to 10–12 hours for extended-release formulations. If no adverse effects develop, the patient can be discharged after the monitoring period.

Calcium channel blockers (eg, diltiazem, amlodipine, nifedipine, verapamil, felodipine, nimodipine, nisoldipine) inhibit L-type (slow or long-lasting) voltage-sensitive calcium channels that are found primarily in cardiac and arterial smooth muscle. L-type calcium channels are also found in the pancreas, skeletal muscle, lung, and brain. L-type calcium channels play an important role in the regulation of cardiac rate and rhythm.

The most common clinical signs of calcium channel blocker toxicoses are hypotension, bradycardia, or reflex tachycardia and arrhythmias, GI upset, CNS depression, hypocalcemia, hyperglycemia, hypo- or hyperkalemia due to insulin shifts, and noncardiogenic pulmonary edema. Clinical signs generally occur within 4 hours after ingestion and can persist for 24–48 hours, with longer durations possible for extended-release formulations. Toxic doses vary with the specific drug.

Management of acute calcium channel blocker toxicosis includes decontamination, correction of hypotension, and monitoring for rhythm disturbances. In general, emesis should be induced within 2 hours after ingestion only if the patient shows no clinical signs. Induction of emesis in patients with clinical signs is contraindicated because it can increase vagal tone and worsen bradycardia.

Activated charcoal binds unabsorbed drug in the GI tract and is most useful when administered within the first few hours after ingestion. If an extended-release product was ingested, one repeat dose of activated charcoal 6–8 hours after the initial dose can provide additional benefit.

Vital signs (including heart rate, blood pressure, and cardiac rhythm) and serum calcium concentrations should be monitored for the duration of a hospital stay for calcium channel blocker toxicosis. Specific treatments should be based on blood pressure, heart rate, ECG, and blood chemistry profiles. Treatments include the administration of IV fluids and calcium gluconate (10% solution at 0.5–1.5 mL/kg, slow IV over 2–5 minutes) for clinically affected patients (1), regardless of serum calcium concentration, to increase calcium availability to cardiac and smooth muscle.

Atropine (0.02–0.04 mg/kg, IM or IV, to effect, repeated as needed) may be administered for bradycardia if calcium gluconate is not available or is ineffective (2).

For persistent hypotension not corrected by the administration of IV fluids and calcium, dopamine (1–15 mcg/kg/min, diluted in saline solution [0.9% NaCl] or 5% dextrose if needed, starting at the low end of the dosing range and titrating to effect) (3, 4) or dobutamine (2–20 mcg/kg/min, diluted in saline solution (0.9% NaCl) or 5% dextrose, starting at the low end of dosing range and titrating to effect) (5, 6) may be given via continuous IV infusion, to effect. In cats, dobutamine should be used with caution because doses > 5 mcg/kg/min can cause CNS signs (7). High-dose insulin and glucagon are additional therapies used for their positive inotropic effect, with varied success, in cases with persistent hypotension or bradycardia.

IV lipid emulsion (ILE) therapy substantially increases the likelihood of a successful outcome in severely affected patients. Because calcium channel blockers are lipophilic, ILE can help sequester calcium channel blockers in overdose situations. The recommended dose of 20% lipid emulsion solution in dogs is 1.5 mL/kg, IV, as an initial bolus, followed by 0.25 mL/kg per minute for 30–60 minutes. A 1.5-mL/kg bolus may be repeated every 4–6 hours if serum lipemia has cleared (1). If the patient does not respond after 3–4 doses, a response is unlikely, and ILE should be discontinued.

Serum color and the patient's response should be monitored during ILE therapy. If serum color is yellow or lipemic, repeating the dose should be delayed until it becomes clear. Although rare, adverse effects of ILE can include hyperlipidemia, infection, intravascular hemolysis, lack of efficacy, and embolism.

Because of extensive protein binding by calcium channel blockers, hemodialysis is not believed to be beneficial in cases of calcium channel blocker toxicosis. In general, patients should be monitored for 8–10 hours after exposure, or up to 10–12 hours for extended-release formulations. If no adverse effects develop, the patient may be discharged after that monitoring period.

Beta blockers (eg, propanolol, metoprolol, atenolol, timolol, esmolol, bisoprolol, sotalol, nadolol) act by competitively inhibiting catecholamine binding to beta-adrenergic receptor sites. Three types of beta-adrenergic receptors are present throughout the body; beta-1 and beta-2 receptors have the most prominent effects on cardiac and vascular tissue. Beta-1-adrenergic receptors increase heart rate and contractility; beta-2-adrenergic receptors mediate vasodilation, bronchodilation, uterine relaxation, and enhanced glycogenolysis in the liver.

The most common clinical signs of beta-blocker toxicosis are bradycardia and hypotension. Hypoglycemia, hyperkalemia, respiratory depression, coma, and seizures are less common signs. Clinical signs of toxicosis generally occur within 4 hours after ingestion, and they can persist for 24–48 hours, or longer for extended-release formulations. Toxic doses vary with the specific drug.

Because beta blockers are rapidly absorbed, emesis should be induced only within 2 hours after ingestion, and only in patients with no clinical signs, as discussed above for calcium channel blockers. Activated charcoal binds unabsorbed drug in the GI tract and is most useful when administered within the first few hours after ingestion; if an extended-release product was ingested, one repeat dose of activated charcoal 6–8 hours after the initial dose can provide additional benefit.

Vital signs (including heart rate, blood pressure, and cardiac rhythm) should be monitored for the duration of a hospital stay for beta-blocker toxicosis. If cardiovascular signs develop, blood glucose and electrolytes should be monitored as well. Hypotension is often successfully treated with IV fluids. Atropine is recommended for bradycardia, and 2.5–5% dextrose supplementation is recommended for hypoglycemia. ILE therapy or administration of glucagon or high-dose insulin (for their positive inotropic effects) are additional therapeutic options, if needed (see Calcium Channel Blocker Toxicoses). If hyperkalemia is confirmed, administration of insulin, followed by IV glucose, can drive the excess potassium back into cells.

Hemodialysis can be beneficial for certain beta-blocker toxicoses; however, the response is not consistent throughout the class. In general, patients should be monitored for 8–10 hours after ingestion, or up to 10–12 hours for extended-release formulations. If no adverse effects develop, the patient may be discharged after that monitoring period.

Oral diuretic agents include thiazides (eg, chlorothiazide, hydrochlorothiazide); loop diuretics (furosemide, torsemide, bumetanide); and potassium-sparing agents (spironolactone, amiloride, triamterene). Injectable osmotic diuretics include mannitol and urea.

Overall, oral diuretics have a wide margin of safety in dogs and cats; the most common clinical signs of toxicosis include vomiting, depression, transient polyuria/polydipsia, and electrolyte changes such as hyper- or hypokalemia. Abnormal electrolyte concentrations can result in muscle weakness and arrhythmias. Electrolyte abnormalities, especially hypo- or hyperkalemia, are more common after a large diuretic ingestion.

Clinical signs of diuretic toxicosis typically occur within 2–4 hours after ingestion for most diuretics and last 6–24 hours. Management should include monitoring hydration and electrolytes, correcting abnormalities as needed, and administering IV fluids. Monitoring patients for 6–8 hours after ingestion is recommended.

Angiotensin II receptor blockers (ARBs)—eg, azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan) block angiotensin II from binding to the angiotensin AT1 receptor, thereby inhibiting the renin-angiotensin system. The result is vasodilation with decreased systolic blood pressure and improved renal function.

ARBs also have direct cardiac effects, including decreased ventricular arrhythmias, improved diastolic function, and improved left ventricular hypertrophy.

The margin of safety of ARBs varies within this class of drugs. Clinical signs of ARB toxicosis include vomiting, hypotension with reflex tachycardia or bradycardia, lethargy, ataxia, and possibly hyperkalemia. Clinical signs can develop within 1 hour after ingestion and persist for up to 24 hours. Emesis should be induced only within the first hour after ingestion.

Because of the rapid absorption of ARBs and rapid onset of signs in cases of toxicosis, activated charcoal is recommended only when very large amounts have been ingested. Vital signs (including heart rate and blood pressure) should be monitored for the duration of a hospital stay for ARB toxicosis.

IV fluids should be given and electrolytes monitored to facilitate the treatment of any clinical signs that develop. Patients should be monitored for 4–6 hours after ingestion; if no signs develop in that monitoring period, the patient may be discharged.

• Peterson ME, Talcott PA, eds. Small Animal Toxicology. 3rd ed. Elsevier/Saunders; 2013.

• Gupta RC ed. Veterinary Toxicology: Basic and Clinical Principles. 4th ed. Academic Press; 2025.

• Also see pet owner content regarding poisonings from human prescription drugs.

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3. Wohl JS, Clark TP. Pressor therapy in critically iII patients. J Vet Emerg Critic Care. 2000;10(1):21-34. doi:10.1111/j.1476-4431.2000.tb00003.x

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6. CEG Formulary: Cardiac Medications for Dogs. Cardiac Education Group. January 2014. Accessed September 12, 2025.

7. Fox PR. Feline myocardial diseases. In: Proceedings of the 18th Annual Waltham/OSU Symposium for the Treatment of Small Animal Diseases: Cardiology. Waltham USA; 1994:117.