Beta Blocker Effects and Side Effects

Products

Beta-blockers are available in many countries in the form of tablets, film-coated tablets, sustained-release tablets, as capsules, solution, eye drops, and as injection and infusion solutions. Propranolol (Inderal) was the first representative of this group to appear on the market in the mid-1960s. Today, the most important active ingredients include atenolol, bisoprolol, metoprolol and nebivolol (see below). Beta-blockers is the abbreviation for the term beta-adrenoceptor antagonists.

Structure and properties

Beta-blockers often exist as racemates. Both enantiomers may have different activities. A distinction is made between lipophilic and hydrophilic beta blockers.

Effects

Beta-blockers (ATC C07) have antihypertensive, antianginal, peripheral vasoconstrictor, and antiarrhythmic properties. They act on the conduction system and contractility of the heart (beta1 receptors):

  • Negative chronotropic: reduction of heart rate.
  • Negative inotropic: reduction in cardiac contractility.
  • Negatively dromotropic: decrease in AV conduction velocity.

This lowers cardiac work and oxygen consumption. Furthermore, the beta-blockers inhibit the release of renin and lower intraocular pressure at the eye. Especially the non-selective beta blockers can lead to bronchoconstriction (beta2 receptors). The effects are due to competitive antagonism at beta-adrenoceptors (beta1 and/or beta2), i.e., displacement of the natural ligands norepinephrine and epinephrine. Beta-blockers belong to the group of sympatholytics, i.e., they abolish effects of the sympathetic nervous system, a portion of the autonomic nervous system.

Classification of beta blockers

  • Selectivity: nonselective beta blockers such as propranolol bind to both beta1 and beta2 receptors. Selective binding to beta1 receptors (eg, metoprolol) is considered an advantage. It is also referred to as cardioselectivity because beta1 receptors are found in high concentrations in the heart. The selective beta blockers are less likely to cause bronchoconstriction (beta2). Beta2 receptors also occur in the vessels. The selectivity is not absolute and dose-dependent.
  • Classification into hydrophilic beta blockers (e.g., atenolol) and lipophilic beta blockers (e.g., propranolol).
  • Vasodilating beta-blockers have vasodilating properties. These include, for example, carvedilol and labetalol, which are also alpha blockers. Nebivolol dilates the vessels by promoting the release of nitric oxide (NO).

Other criteria:

  • Beta-blockers with or without intrinsic sympathomimetic activity (ISA), e.g., pindolol. It is also referred to as partial agonistic activity at the beta receptor.
  • Membrane-stabilizing (local anesthetic) beta-blockers, e.g., propranolol, sotalol.

Indications

Cardiovascular:

  • High blood pressure (hypertension)
  • Chronic heart failure
  • Cardiac arrhythmias, e.g. supraventricular tachyarrhythmias.
  • Long-term prophylaxis of angina pectoris (coronary artery disease).
  • Prophylaxis after a heart attack
  • Functional cardiovascular disorders with palpitations

Nervous system:

  • Migraine prophylaxis
  • Anxiety-related acute somatic symptoms and tachycardia (e.g., excitement, stage fright), especially propranolol
  • Essential tremor

Eye disorders:

Adrenal medullary diseases:

Thyroid disorders:

  • Hyperthyroidism
  • Thyrotoxic crisis

Dermatology:

Dosage

According to the professional information. The dosing interval depends on the half-life of the active ingredients.

Abuse

Beta-blockers can be misused as doping agents in sports where a steady hand is required and are therefore banned. These include, for example, archery and billiards.

Active substances

Beta-blockers usually contain the suffix -olol. Nonselective beta blockers (beta1 and beta2 receptors):

  • Propranolol (Inderal, generic).
  • Sotalol (Sotalex, generic)

Beta1-selective beta blockers:

With α1-blocking effect:

  • Carvedilol (Dilatrend, generic).
  • Labetalol (Trandate)

For glaucoma therapy:

Other agents exist that are not or no longer commercially available in many countries.

Contraindications

Contraindications include (selection):

  • Hypersensitivity
  • Bradycardia
  • Cardiogenic shock
  • Hypotension
  • Metabolic acidosis
  • Severe peripheral circulatory disturbances
  • AV block
  • Sick sinus syndrome
  • Decompensated heart failure
  • Peripheral arterial occlusive disease, Raynaud’s syndrome
  • Untreated pheochromocytoma
  • Bronchospasm
  • Bronchial asthma (v.a. non-selective agents).

For complete precautions, see the drug label.

Interactions

Drug-drug interactions are possible with other antihypertensives and with other drugs that affect the cardiovascular system, e.g., antiarrhythmics. Calcium channel blockers should not be administered concomitantly. Some beta-blockers are substrates of CYP450 isoenzymes, e.g., metoprolol. When antidiabetic agents are used, it is important to note that beta blockers can mask symptoms of hypoglycemia.

Adverse effects

The most common potential adverse effects include fatigue, weakness, dizziness, bradycardia, cold extremities, hypotension, and gastrointestinal disturbances. Respiratory disturbances and bronchoconstriction are most common with nonselective beta-blockers.