Beta blockers for hypertension

There are three subtypes of β-adrenergic receptors  (β1, β2 and β3) that mediate a wide range of physiological responses to the adrenergic agonists adrenaline and noradrenaline. These receptors are the target of beta adrenergic blockers (aka beta blockers) used in the management of cardiovascular diseases .

Beta-blockers are used to treat hypertension, dysrhythmias such as atrial fibrillation, and systolic congestive heart failure. Other less common indications include anxiety, prophylaxis of migraine headache  and stage fright.

Beta adrenergic receptor inhibition at β-1 adrenergic receptors causes reduced heart rate, conduction velocity and contractility. Non-selective β-blockers also antagonize beta-2 receptors, causing bronchoconstriction (asthama-like reactions) and arteriolar vasoconstriction (and increased systolic BP).

Beta-blockers show a varying amount of the four properties-cardioselectivity, lipid solubility, Intrinsic sympathomimetic activity, membrane stabilization-and thus important to consider them when selecting a beta-blocker for a specific condition.

Cardioselectivity: All beta-blockers act upon both beta-1 and beta-2 receptors. At therapeutic doses, cardioselective beta-blockers, such as Acebutolol, Atenolol, Betaxolol, Bisoprolol, Metoprolol act upon beta-1 receptors (in the heart) much more than the beta-2 receptors (found in the bronchioles of the lungs and the arteries of the skeletal muscles); but this selectivity is lost in overdose. 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 (Metoprolol, Propranolol, Timolol), can cross the blood-brain barrier easily to cause CNS effects. For their ability to enter the CNS, these medications are commonly used in the management of migraine headaches, stage fright and panic attacks.

Intrinsic sympathomimetic activity (ISA): Beta-blockers with ISA, such as Acebutolol, Carteolol (moderate ISA), Penbutolol, Pindolol (significant ISA), retains 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 drugs are often preferred in younger patients, or in athletes where heart rate needs to elevate in order to compete in sports and participate in physical fitness exercises.

Membrane stabilization: Membrane stabilizing effects (sodium channel blocking effects) of propranolol (and also acebutolol, nadolol and pindolol) decreases the propagation of action potentials (Just like local anaesthetics and class I antiarrhythmics). This may be the mechanism by which propranolol treats migraine headaches and causes CNS effects (depression and seizures).

Alpha-receptor blockade: Alpha adrenergic blocking activity of carvedilol and labetalol may result in pronounced hypotension through peripheral vasodilation, which together with  cardio-activity, is beneficial in severely hypertensive patients.

Because beta-blockers may mask the symptoms of hypoglycemia (sweating, tachycardia) in diabetic patients. Diabetic patients on these drugs should closely monitor their sugar levels to avoid hypoglycemic episodes.

Water soluble beta blockers including sotalol, atenolol, bisoprolol and labetalol are predominantly renally excreted and may accumulate to toxic levels in the presence of renal failure; monitor closely renal function especially in the elderly patients.

Beta‐blocker overdose is potentially harmful due to the strong blood pressure‐lowering and heart rate‐lowering effect, and the mechanism of action of the drug prevents normal physiological compensation and limits the effectiveness of many standard therapies.

The common effects associated with beta-blockers overdose include: Bradycardia, hypotension and cardiovascular collapse. Uncommonly, CNS effects including seizures, may be seen with propranolol.

Cardiac toxicity and death is most commonly observed in patients with underlying cardiovascular diseases; the elderly due to decreased cardio-respiratory reserve; after  co-ingestion cardioactive agents like digoxin and calcium channel blockers; and overdoses of beta blockers with membrane-stabilizing effects such as propranolol, and acebutolol or those that induce ventricular dysrhythmias (torsades de pointes) such as sotalol.
For a more comprehensive review of betablocker overdose click Beta receptor blockers link

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