β-Blockers

Chapter 191 β-BLOCKERS

Betsy R. Bond, DVM, DACVIM (Cardiology)

• β-Adrenergic blockers are one of our oldest and most commonly used medications in veterinary cardiology, and they have a multitude of uses in many different areas.

• The most common use of β-blockers is for supraventricular and ventricular arrhythmias.

• Although they have been used for systemic hypertension, they are not as effective as other medications.

• Esmolol is one of best β-blockers to use in the critical care setting because it has a short duration of action and can be given in a constant rate infusion.

• β -Blockers should be used with caution in animals with congestive heart failure and systolic dysfunction because of their negative inotropic effects.

• Although β-blockers are administered with increasing frequency in human patients with dilated cardiomyopathy, this use is just now being studied in veterinary medicine. The potential benefits of using β-blockers in dogs with mitral regurgitation are also not known.

• There is controversy about the use of β-blockers in cats with cardiomyopathy.

INTRODUCTION

For a long time, β-adrenergic receptor blockers have been important treatment options in both human and veterinary medicine, although they have only been used to manage mild to moderate congestive heart failure (CHF) in humans for the last 10 years. The use of β-blockers for heart failure represented a dramatic theoretic change because physicians previously believed that β-blockers were contraindicated in any kind of CHF.¹ Although frequently used for certain cardiomyopathies and arrhythmias in veterinary medicine, β-blockers may be underutilized in dogs and cats with CHF.

On the other hand, they have immense value in the critical care setting because of their usefulness in diverse situations. For example, using the ultra–short-acting drug esmolol for an arrhythmia can test the efficacy of β-blockers without overtly compromising the patient. Once β-blockers have proven beneficial, longer acting agents or a constant rate infusion (CRI) of esmolol may be prescribed.

PATHOPHYSIOLOGY OF β-ADRENERGIC RECEPTORS

Classically, β-receptors are divided into β₁-receptors, found in the heart muscle, and β₂-receptors, located primarily in bronchial and vascular smooth muscle but also found in cardiac muscle. β₃-Receptors also exist, but because their existence and function in the critical care setting are not well known, they will not be discussed here. β-Receptors are coupled to adenylcyclase by a stimulatory G protein; this coupling causes the formation of cyclic adenyl monophosphate (cAMP). cAMP is a second messenger with two primary effects in the heart muscle: (1) a positive inotropic effect (an increase in the rate and force of myocardial contraction) and (2) a relaxing or lusitropic effect (by facilitating reuptake of calcium into the sarcoplasmic reticulum). In the sinus node there are both chronotropic (increased rate of firing) and dromotropic (accelerated rate of conduction) effects that combine to increase the heart rate.² Beta stimulation can also stimulate growth of cardiomyocytes and cause the particularly deleterious effects of myocyte toxicity and apoptosis.¹

The failing human heart has an increased adrenergic drive, which supports the heart in early, acute stages, but it ultimately causes damage to the myocardium in the chronic state.^1,3 In normal human ventricles the number of β₁-receptors is much greater than β₂-receptors, but the ratio is reversed in failing ventricles because of selective downregulation of β₁-receptors.¹ The altered ratio of β₁ and β₂ receptors has also been shown in a canine model of induced heart failure.⁴

MECHANISMS OF ACTION

Generations of β-Blockers

Although β-blockers are only one class of drugs, their effects are extremely varied and are determined by their pharmacologic properties: selective versus nonselective, presence or absence of intrinsic sympathomimetic activity, and additional actions (e.g., carvedilol is a nonselective β-blocker with α-adrenergic vasodilatory properties). Division of the various β-blockers is by generations.²

First-generation β-blockers are nonselective, blocking both β₁-adrenergic and β₂-adrenergic receptors.^1,2 Propranolol is the prototypical first-generation agent and has been used the longest in veterinary medicine.

Second-generation β-blockers are known as selective β-blockers because at normal dosages they are more cardioselective, acting predominantly on β₁-receptors rather than β₂-receptors. Atenolol and metoprolol are selective β-blockers and have the advantage of generating less bronchospasm or any other side effect that might arise from β₂-blockade.

Third-generation β-blockers such as carvedilol are nonselective and have the additional property of being vasodilators through α₁-blockade.^1,2,5

β-Blockers are also recognized as class II antiarrhythmic drugs in the Vaughan-Williams classification.

Tags: Small Animal Critical Care Medicine

Sep 10, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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