Cardiovascular Medications (Toxicity)

Several angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril, captopril, lisinopril, benazepril) are used therapeutically to treat congestive heart failure in dogs and cats. The primary concern in cases of acute ACE inhibitor overdose is usually marked hypotension. If hypotension is severe, secondary renal damage may result. Onset occurs within a few hours of exposure, depending on the agent (extended-release formulations may have a delayed onset of action). Other clinical signs of overdose may include vomiting, poor mucous membrane color, weakness, and tachycardia or bradycardia. Activated charcoal is effective in binding the drug from the GI tract if administered within 1–2 hr of ingestion. Blood pressure should be monitored and IV fluids given at twice the maintenance rate if hypotension develops. Renal function should be monitored if severe or persistent hypotension develops.

Calcium channel blockers (eg, diltiazem, amlodipine, nifedipine, verapamil) inhibit movement of calcium from extracellular sites through cell membrane–based calcium channels. The most common signs seen with overdoses of calcium channel blockers are hypotension, bradycardia, GI upset, noncardiogenic pulmonary edema, and heart block. Reflex tachycardia may develop in response to the drop in blood pressure.

Management of an acute overdose includes correcting hypotension and rhythm disturbances. In general, emesis is induced within 2 hr of ingestion only if the animal is showing no clinical signs. Induction of emesis in animals with signs can increase vagal tone and worsen the bradycardia. Activated charcoal binds unabsorbed drug in the GI tract and is most useful when administered within the first few hours after ingestion; if a sustained-release product was ingested, repeat doses of activated charcoal every 4–6 hr for a total of 2–4 doses can provide additional benefit. Specific therapies should be instituted based on blood pressure, heart rate, ECG, and blood chemistry profiles. IV fluids are recommended; calcium gluconate (10% solution at 0.5–1.5 mL/kg, slow IV) should be added while monitoring the ECG closely. Atropine (0.02–0.04 mg/kg) can be given for bradycardia; isoproterenol can be used if the ECG indicates atrioventricular block. For persistent hypotension not corrected by administration of IV fluids, synthetic colloids (Hetastarch), dopamine (1–20 mcg/kg/min), or dobutamine (2–20 mcg/kg/min) can be given via continuous IV infusion. A temporary cardiac pacemaker may be needed in cases of severe cardiac conduction disturbances unresponsive to medical therapy. Calcium channel blockers may interact with almost any other cardioactive medication, resulting in more profound bradycardia, hypotension, and depression of cardiac contractility. Because of the lipophilic nature of calcium channel blockers, using IV lipid emulsion solution (Intralipid^TM 20% solution) may help sequester calcium channel blockers in overdose situations and prevent them from reaching their site of action. 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/min for 30–60 min. This dose can be repeated in 6 hr for a total of three treatments. Serum color and response should be monitored. If serum color is yellow, repeating the dose should be delayed until it becomes clear. If no response is seen after three doses, lipid emulsion should be discontinued. Hyperlipidemia, infection, intravascular hemolysis, lack of efficacy, and embolism are potential adverse effects associated with IV lipid emulsion therapy. The use of IV lipid emulsion for the treatment of some lipophilic drug overdoses is experimental and should be considered only if other conventional treatment options fail. Efficacy and safety of IV lipid emulsion has not been studied.

Drugs in this class (eg, propanolol, metoprolol, atenolol, timolol, esmolol) act by competitively inhibiting catecholamine binding to β-adrenergic receptor sites. The most common signs of overdose are bradycardia and hypotension; respiratory depression, coma, seizures, hyperkalemia, and hypoglycemia may occur. It is also possible to precipitate congestive heart failure. Significant clinical signs may arise even at therapeutic (published) doses—no approved veterinary products are on the market.

Because of rapid absorption, emesis should only be induced in asymptomatic animals within 2 hr of ingestion. Administration of activated charcoal should be considered if either multiple tablets or capsules or sustained-release formulation tablets are ingested. Heart rate, blood pressure, and clinical condition should be monitored for several hours, because extended-release pills can lead to delayed onset of clinical signs. If clinical signs do develop, blood chemistries should also be measured. Hypotension should be treated with IV fluids; atropine can be used for bradycardia. Glucagon or isoproterenol can also be used if needed ( see Calcium Channel Blockers). If hyperkalemia is confirmed, administration of insulin, followed by IV glucose, may drive the excess potassium back into the cells.

Phenylpropanolamine (PPA) is a sympathomimetic amine used primarily for treating urinary incontinence in dogs and cats. PPA is believed to indirectly stimulate both α- and β-adrenergic receptors, causing the release of norepinephrine. It is rapidly absorbed orally and distributes to various tissues, including the CNS. PPA is mainly excreted through the kidneys as a parent drug. Overdose of PPA can result in CNS effects (restlessness, agitation, nervousness) and cardiovascular signs (hypertension or hypotension, tachycardia or bradycardia, premature ventricular contractions, cardiovascular collapse). Dogs can also show piloerection, hyperemia, vomiting, hyperthermia or hypothermia, and mydriasis. Treatment consists of early decontamination (emesis in asymptomatic animals within a couple of hours of ingestion, followed by administration of activated charcoal). CNS effects and mild hypertension can be managed with acepromazine (0.02 mg/kg, IV or IM, repeated as needed). A nitroprusside constant-rate infusion can be tried for hypertension not responsive to acepromazine. Lidocaine can be considered for treating premature ventricular contractions. IV fluids should be given to promote excretion. Other signs should be treated symptomatically.

Oral diuretic agents include thiazides (eg, chlorothiazide, hydrochlorothiazide), loop diuretics such as furosemide, and potassium-sparing agents such as spironolactone (an aldosterone antagonist) and triamterene. Osmotic diuretics, administered by injection, include mannitol and urea. The most common signs of diuretic overdose include vomiting, depression, polyuria and polydipsia, and electrolyte changes. Electrolytes, especially potassium, may shift subsequent to a large ingestion of a diuretic. Management should include monitoring hydration and electrolytes, with correction as needed.