Mechanism of Action
Beta-blockers antagonize beta-1 and beta-2 receptors which are the usual targets of the sympathetic nervous system, including epinephrine and norepinephrine. This results in a decreased heart rate through decreased SA node activity and decreased AV nodal conduction, as well as decreased inotropy — contractility — of the heart.
Beta-blockers are used to treat hypertension, tachyarrhythmias such as atrial fibrillation, and systolic congestive heart failure. Other less common indications include anxiety, migraine headache prophylaxis and stage fright.
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- exacerbation of systolic heart failure,
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The four different properties of beta-blockers are:
- lipid solubility,
- intrinsic sympathomimetic activity, and
- membrane stabilization.
Each beta-blocker has a different amount of these properties and it is important to consider these when selecting a beta-blocker for a specific condition. The chart below summarizes which beta-blockers possess each property.
Cardioselectivity: All beta-blockers act upon both beta-1 and beta-2 receptors. The “cardioselective” beta-blockers act upon beta-1 receptors much more than the beta-2 receptors. For this reason, the cardioselective beta-blockers are safer to use in patients with asthma or reactive airway diseases.
Lipid solubility: Beta-blockers that are lipid soluble, such as propranolol or metoprolol, can cross the blood-brain barrier easily. These medications are commonly used for migraine headaches, stage fright and panic attacks for these reasons.
Intrinsic sympathomimetic activity (ISA): Beta-blockers with ISA only partially antagonize while actually causing a small degree of activation of the beta receptors. Therefore, they will have some beta-blocking effects, but not to the degree of beta-blockers without ISA. These are commonly used in younger patients or in athletes where heart rates need to elevate (allowing overall increased cardiopulmonary effort) in order to compete in sports. Examples include pindolol and acebutolol.
Membrane stabilization: Stabilizing membranes decreases the propagation of action potentials. This is also the mechanism that local anesthetics work (lidocaine). Class I antiarrhythmic drugs possess this characteristic as well. The importance of this is not clear in clinical medicine in regards to beta-blockers. Perhaps this is partially an explanation for propranolol treating migraine headaches.
Beta-blockers should be initiated in patients hospitalized for acute systolic congestive heart failure prior to hospital discharge. It is reasonable to withhold beta-blockers in patients who were previously taking them in the outpatient setting for chronic systolic heart failure when they are admitted with a heart failure exacerbation.
Beta-blockers are contraindicated specifically in systolic heart failure when pulmonary edema is present, when there are signs of cardiogenic shock, severe bradycardia, hypotension or wheezing related to asthma.
Beta-blockers are contraindicated during an acute myocardial infarction when there are signs of pending cardiogenic shock. These include systolic blood pressure < 110 mmHg and pulmonary edema. Typical contraindications include severe bradycardia, heart block more advanced than first degree (unless a pacemaker is in place) and for use during a MI from cocaine use.
Esmolol has a very short half-life and is used as a continuous IV drip.
Beta-blocker overdose can be life-threatening. The treatment is glucagon and dobutamine/milrinone.
Beta-blockers cause insulin resistance, decrease high density lipoprotein levels and increase triglyceride levels.
Beta-blockers mask the symptoms of hypoglycemia in diabetic patients, which is predominantly mediated through the sympathetic nervous system (sweating, tachycardia).