What do beta (beta) blockers do?

Beta-Blockers: Mechanism of Action and Clinical Applications

Beta-blockers competitively inhibit the effects of catecholamines on beta-adrenergic receptors, reducing heart rate, blood pressure, and myocardial contractility, thereby decreasing myocardial oxygen demand and providing therapeutic benefits in various cardiovascular and non-cardiovascular conditions. 1

Mechanism of Action

Beta-blockers work by:

• Blocking beta-adrenergic receptors, preventing catecholamine binding
• Inhibiting activation of adenylyl cyclase and subsequent cAMP production
• Decreasing phosphorylation of L-type calcium channels
• Reducing calcium influx into cardiomyocytes 1

Classification Based on Receptor Selectivity

Beta-blockers can be classified into:

1. Beta-1 selective agents (cardioselective):

   • Primarily affect cardiac beta-1 receptors
   • Examples: metoprolol, atenolol, bisoprolol
   • Preferred due to fewer side effects related to beta-2 blockade 1
   • Selectivity diminishes at higher doses 2

2. Non-selective agents:

   • Block both beta-1 and beta-2 receptors
   • Examples: propranolol, timolol
   • Can cause vasoconstriction and bronchoconstriction 1

3. Vasodilating beta-blockers:

   • Combine beta-blockade with vasodilation
   • Examples: carvedilol, labetalol
   • Cause less depression of exercise cardiac output than ordinary beta-blockers 3

Hemodynamic Effects

• Decreased heart rate and contractility reduce cardiac output and myocardial oxygen demand
• Reduced systolic blood pressure lowers afterload
• Prolonged diastole increases coronary perfusion time 1
• Ordinary beta-blockers do not reduce total peripheral resistance much below pretreatment level 3
• Vasodilating beta-blockers induce both decreased pressure-heart rate product and some reduction in total peripheral resistance 3

Clinical Applications

Cardiovascular Conditions

1. Hypertension:

   • Reduce blood pressure by decreasing cardiac output and inhibiting renin release 4
   • Often combined with diuretics for enhanced effect 4

2. Angina Pectoris:

   • Decrease myocardial oxygen demand
   • Control heart rate and blood pressure
   • Provide antiarrhythmic properties 1

3. Heart Failure:

   • Selective agents (metoprolol, bisoprolol) and carvedilol demonstrate mortality benefit 5
   • Should be used with caution as sympathetic stimulation may be vital for circulatory function 6
   • Require careful follow-up in patients with history of failure 6

4. Post-Myocardial Infarction:

   • Nonselective agents without intrinsic sympathomimetic activity are most appropriate 5
   • Propranolol, timolol, metoprolol, and carvedilol (in presence of LV dysfunction) demonstrate mortality benefit 5

5. Arrhythmias:

   • Provide stabilization of electrical activity 1

Non-Cardiovascular Applications

1. Glaucoma:

   • Topical beta-blockers reduce intraocular pressure by decreasing aqueous humor production 4
   • Oral beta-blockers also reduce intraocular pressure but are not primary treatment 4

2. Thyrotoxicosis/Hyperthyroidism:

   • Manage increased heart rate, tremor, and nervousness
   • Propranolol is most widely studied for this purpose 4
   • May inhibit peripheral conversion of T4 to T3 4

3. Migraine Headache:

   • Effective for prophylaxis 4

4. Essential Tremor:

   • Reduce tremor amplitude 4

5. Anxiety Disorders:

   • Help manage performance anxiety and other anxiety disorders 4

Important Considerations and Cautions

Abrupt Discontinuation

• Never abruptly discontinue beta-blockers in patients with coronary artery disease
• Severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias may occur
• When discontinuation is planned, gradually reduce dosage over several weeks 6, 2

Specific Contraindications and Cautions

1. Bronchospastic Disease:

   • Non-selective beta-blockers may worsen bronchospasm
   • Beta-1 selective agents may be used with caution in patients who do not respond to other treatments 2

2. Diabetes:

   • May mask tachycardia occurring with hypoglycemia
   • Use with caution in diabetic patients 2

3. Heart Failure:

   • May precipitate more severe failure in uncompensated patients
   • Requires careful monitoring 6

4. Thyroid Disease:

   • May mask signs of hyperthyroidism
   • Abrupt withdrawal may precipitate thyroid storm 6, 2

5. Peripheral Vascular Disease:

   • Non-selective agents may worsen symptoms 4

6. Pregnancy:

   • Can cause fetal harm
   • Associated with birth of infants small for gestational age 2

Selection of Specific Agents

• Selection should be guided by available trial data and patient-specific factors 5
• Not all beta-blockers are associated with survival benefit in all conditions 5
• Cardioselective agents are preferred in patients with certain comorbidities 1
• Vasodilating beta-blockers may offer advantages in maintaining exercise cardiac output and organ perfusion 3

Beta-blockers remain a cornerstone of cardiovascular therapy more than 50 years after their introduction, with evolving understanding of their differential effects and optimal use in various clinical scenarios.