CHAPTER 40 Cardiovascular Pharmacology
Compared with human medicine, the therapeutic options for the treatment of cardiovascular disease in horses are limited to a relatively small group of agents (Table 40-1). Most recommendations for the use of cardiovascular agents in horses are based on empirical data rather than scientific evidence, and the efficacy and safety of most drugs have not been well investigated in horses. Generally, cardiovascular drugs are used for treatment of arrhythmias, treatment of heart failure, and support of cardiovascular function in a variety of clinical situations. Prophylactic therapy or long-term treatment of horses with subclinical disease (to slow progression of disease) is rarely performed, mostly because of a lack of evidence of clinical efficacy, doping concerns in sports horses, and financial constraints.
In any instance, the benefits and potential risks of cardiovascular drug treatment should be carefully considered, and treatment should be performed under close clinical supervision, with electrocardiographic (ECG) monitoring, arterial blood pressure monitoring, and (where applicable) measurement of plasma or serum drug concentrations. Treatment of coexisting conditions, adequate hydration, oxygenation, and correction of existing electrolyte (i.e., K+, Mg2+) and acid-base disturbances must precede or accompany cardiovascular drug treatment and can critically influence drug efficacy and the incidence of adverse drug effects. In critically ill horses, monitoring of cardiac output, vascular resistance, oxygen delivery and extraction, and blood lactate concentrations may be necessary to assess cardiovascular function, choose the most appropriate treatment, adjust drug doses, and evaluate the response to treatment.
Antiarrhythmics are commonly grouped according to the Vaughan Williams classification system in which the drugs are classified in six classes (IA to IV) on the basis of primary mechanism of effect. Some agents, such as amiodarone, exert effects that are consistent with several of these classes, whereas other agents, for example, magnesium, are not included in this classification. It is important to realize that most antiarrhythmics can also have proarrhythmic effects that could be detrimental to the horse’s health.
Class IA Drugs
Quinidine and procainamide are class IA sodium channel blockers that slow impulse conduction through the heart. They also inhibit repolarizing potassium currents, thereby prolonging the action potential duration and the QT interval and increasing the refractoriness of the myocardial cells. These drugs also have anticholinergic and vasodilatory effects.
Quinidine is used primarily for conversion of atrial flutter or atrial fibrillation (AF) to sinus rhythm, with a reported efficacy as high as 80% to 90%. Horses with AF and high resting heart rate, evidence of impaired left-ventricular systolic function (based on echocardiography), or congestive heart failure should be pretreated with furosemide (to control edema) and digoxin (to control heart rate and improve systolic left-ventricular function) as necessary. Adverse effects of quinidine are common, even at therapeutic plasma concentrations. Prolongation of the QRS complex of greater than 25% of baseline indicates toxic plasma concentrations (i.e., greater than 5 mcg/mL). In horses with an accelerated atrioventricular conduction (heart rate greater than 100 beats/minute), the rate may be controlled by intravenous (IV) administration of digoxin, diltiazem, or propranolol with close monitoring of clinical response, ECG changes, and blood pressure. Diltiazem and propranolol may enhance hypotension and negative inotropism and should be administered with caution. If the rate is sustained in excess of 150 beats/minute or severe hypotension occurs, administration of IV sodium bicarbonate (1 mEq/kg) should be considered to antagonize the sodium channel blocking effects of quinidine. Forced diuresis using fluids and diuretics may enhance renal excretion of the drug. Severe hypotension is treated with IV fluids or colloids and phenylephrine or norepinephrine. Ventricular arrhythmias are treated with lidocaine and magnesium sulfate. Hypokalemia and hypomagnesemia may increase the risk of torsades de pointes and should be prevented.
Class IB Drugs
Lidocaine binds to inactivated sodium channels and inhibits membrane recovery after repolarization. Lidocaine acts preferentially at rapid heart rates and on the ischemic or diseased (depolarized) myocardium, where it promotes conduction block and interrupts reentry arrhythmias. It does not prolong the action potential duration and QT interval. Lidocaine is the treatment of choice for ventricular arrhythmias in horses. Concurrent correction of electrolyte imbalances is important, as lidocaine is less effective in the presence of low extracellular potassium and magnesium concentrations. Lidocaine undergoes hepatic clearance, anddoses should be halved in horses with poor liver blood flow from low cardiac output or impaired liver function.
Class IC Drugs
Class IC antiarrhythmics are potent sodium channel inhibitors that slow impulse conduction through the heart and cause variable prolongation of the action potential duration and QT interval. They may be used to control supraventricular and ventricular arrhythmias that are resistant to other drugs. Flecainide has recently been proposed for treatment of acute AF in horses. However, it is ineffective for treatment of horses with chronic AF and has been associated with potentially dangerous ventricular arrhythmias.
Propafenone is a class IC agent that also has weak β-blocking and L-type calcium channel blocking effects. It has been proposed for treatment of quinidine-induced ventricular tachycardia. In general class IC agents should be used with caution, because their efficacy and safety have not been fully investigated in horses.