Beta-Blocker Classification & Effects

Classification of β-Receptor Blockers

• β-blockers can be classified into three main categories: Non-selective, Selective, and those with Vasodilatory (VD) action.

Non-Selective β-blockers (block β1 and β2)

• Propranolol is a non-selective β-blocker that has good CNS penetration and undergoes hepatic metabolism.
• Pindolol is a non-selective β-blocker.
• Timolol is a non-selective β-blocker.

Selective β-blockers (block β1)

• Atenolol has limited CNS penetration and is mainly excreted by the kidneys.
• Bisoprolol is a selective β1-blocker.
• Esmolol is a selective β1-blocker.

β-blockers with VD(Vasodilatory) action

• Carvedilol is a non-selective β-blocker that also has vasodilatory action.
• Nebivolol has the highest β1 selectivity and also exhibits vasodilatory action.

Pharmacological Effects

Cardiovascular (CVS) Effects

• Blocking β1 receptors results in decreased cardiac properties
• Cardiac properties include decreased heart rate (bradycardia), and decreased cardiac output (COP).
• Blood pressure is lowered through reduced COP, decreased renin release from the kidney (via β1 receptors), and decreased norepinephrine (NA) release & central sympathetic outflow.
• Some β-blockers block vascular α1 receptors.
• Some β-blockers increase the synthesis of PGE2 & PGI2, leading to vasodilation (VD).

Respiratory Effects

• Beta blockers can produce bronchospasm.
• This effect can occur even with selective β1-blockers at high doses.
• Beta blockers are generally contraindicated in asthmatic patients.

Eye Effects

• Beta blockers can decrease intraocular pressure (IOP) by reducing aqueous humor secretion; Timolol is used topically

CNS Effects

• Beta blockers can have antianxiety effects.
• Beta blockers can causes night mares.
• Beta blockers can cause sexual dysfunction

Metabolic Effects

• Beta blockers can increases the hypoglycemic effect of insulin due to decreased glycogenolysis in the liver (β2).
• Beta blockers can increases plasma potassium (K+) levels (hyperkalemia) in patients with renal failure.
• Beta blockers can increase plasma triglycerides and decrease HDL levels.

Skeletal Muscle Effects

• Beta blockers are associated with decreased essential tremors due to β2 block in skeletal muscles.

Other Specific Properties

• Pindolol is a partial agonist, meaning that it does not typically cause excessive bradycardia.
• Esmolol is ultra-short acting with a half-life (t 1/2) of 10 minutes, Esmolol is given by IV infusion to control arrhythmia during surgery & emergency.
• Labetalol is a mixed blocker, blocking both β-receptors & α1-receptors.

Therapeutic Uses

• Beta blockers are used in the treatment of hypertension.
• Beta blockers are used in the treatment of ischemic heart disease, specifically classic angina & acute myocardial infarction.
• Beta blockers cause decreased myocardial work & O2 demand and redistribution of blood to the ischemic regions, and offer a cytoprotective effect.
• Beta blockers are used for cardiac arrhythmias, (especially in thyrotoxic patient) by decreasing A-V conduction, automaticity, and excitability using Propranolol as a stabilizing action.
• I.V.I esmolol can treat acute arrhythmia during surgery.
• Beta blockers are used for hypertrophic obstructive cardiomyopathy, as a congenital thickening of ventricular wall & septum
• The outflow resistance to blood flow in aorta are decreased with a reduction in HR & contractility (-ve inotropic)
• Small doses of β-blockers are used in mild to moderate cases of chronic heart failure (HF).
• Those effects include reduced tachycardia & sympathetic over activity, ventricular strain, and inhibit renin release & remodeling.
• Bisoprolol, Metoprolol, & Carvedilol are the most useful with Carvedilol having VD & antioxidant properties.
• Beta blockers are used for hyperthyroidism with Propranolol used to treat tachycardia, anxiety & tremors
• It also prevents peripheral conversion of T4 into T3.
• Propranolol is used for Esophageal varices due to liver cirrhosis by decreasing portal & hepatic blood flow
• COP & VC in the splanchnic vascular beds (an unopposed α-action).
• Topical timolol is used for Glaucoma (open angle).
• Beta blockers along with alpha-blockers are used to combat Pheochromocytoma.
• Propranolol is used for Migraine prophylaxis.
• Propranolol can treat Anxiety.

Adverse Effects

• The most common adverse effects are tiredness & fatigue
• This is due to decreased cardiac output and block of β2-mediated vasodilation (VD) in skeletal muscles and non-selective agents.
• Bradycardia & decreased myocardial contractility.
• Bronchospasm.
• Aggravation of peripheral ischemia.
• CNS: Nightmares & depression.
• Sudden abrupt withdrawal can increase the risk of angina & arrhythmias so Gradual withdrawal is recommended (After prolonged use).

Contraindications

Absolute Contraindications

• Bronchial asthma
• Any degree of heart block
• Vasospastic (Prinzmetal’s) angina
• Acute heart failure & severe chronic heart failure
• Sudden withdrawal after long-term use

Relative Contraindications

• Peripheral vascular diseases (PVD)
• Diabetes mellitus
• Athletes (strenuous sports)
• Hypotension