Adrenergic Antagonists Lecture Notes

Overview

• Adrenergic Antagonists (Sympatholytics)
  • Bind to adrenergic receptors, prevent activation
  • Two main groups: Alpha blockers and Beta blockers

Alpha Blockers

Alpha-1 Adrenergic Antagonists

• Block binding of norepinephrine to smooth muscle receptors
• Results in vasodilation and lowered blood pressure
• Uses: Treatment of hypertension

Subdivisions

Non-Selective Alpha Blockers

• Examples: Phentolamine and Phenoxybenzamine
• Use: Hypertension due to pheochromocytoma
• Mechanism:
  • Block both alpha-1 and alpha-2 receptors
  • Alpha-2 blockade: Increased norepinephrine release -> Stimulates beta-1 receptors on heart -> Tachycardia and arrhythmias
• Differences:
  • Phenoxybenzamine: Irreversible, effects last ~24 hours
  • Phentolamine: Reversible, effects last ~4 hours

Selective Alpha Blockers

• Alpha-1 Blockers:
  • Selectively block alpha-1 receptors in vascular smooth muscle
  • Effect: Reduces peripheral resistance, decreases blood pressure
  • Other sites: Bladder neck and prostate gland -> Relief of urinary difficulties in benign prostatic hypertrophy (BPH)
  • Examples: Prazosin, Doxazosin, Terazosin, Tamsulosin, Alfuzosin, Silodosin
  • Identification: End in "-osin"
  • Specific Uses:
    • Prazosin, Doxazosin, Terazosin: Effective for hypertension, less for enlarged prostate
    • Tamsulosin, Alfuzosin, Silodosin: Effective for BPH, little effect on blood pressure
• Side Effects: Orthostatic hypotension, vasodilation (headaches, nasal congestion)

Alpha-2 Selective Blockers

• Limited clinical application
• Example: Yohimbine
  • Use: Found in dietary supplements, veterinary medicine (reversing sedative effects of alpha-2 agonists)

Beta Blockers

Classification

• Generations: Classified as first, second, or third generation

Mechanism

• Competitive inhibition at beta adrenergic receptors
• Decrease effects of catecholamines (epinephrine, norepinephrine)
• Effects: Decreased sympathetic effects, especially on cardiovascular system
• Uses: Hypertension, heart failure, heart attacks, angina, cardiac arrhythmias, glaucoma, migraine prophylaxis

Generations

First Generation (Non-Selective)

• Block both beta-1 and beta-2 receptors
• Examples: Propranolol, Pindolol, Nadolol, Sotalol, Timolol
• Effects:
  • Blockade of beta-1: Decreased heart rate, delayed AV node conduction, reduced contractility -> Decreased cardiac output, decreased oxygen demand
  • Specific Uses:
    • Propranolol: Migraine prophylaxis (CNS penetration)
    • Timolol: Glaucoma (topically reduces intraocular pressure)
• Side Effects:
  • Blockade of beta-2: Bronchoconstriction -> Not recommended in COPD/asthma patients

Second Generation (Beta-1 Selective, Cardio-Selective)

• Suitable for chronic lung disease patients (at high doses, selectivity may be lost)
• Examples: Atenolol, Acebutolol, Bisoprolol, Esmolol, Metoprolol

Third Generation

• Include both non-selective and selective agents
• Non-Selective Agents: Carvedilol, Labetalol
  • Cause vasodilation by blocking beta and alpha-1 receptors
• Beta-1 Selective Agents: Nebivolol, Betaxolol
  • Vasodilation effects via nitric oxide release (Nebivolol), calcium channel blockade (Betaxolol)
  • Betaxolol also useful in glaucoma (decreases intraocular pressure)
• Special Properties: Antioxidant properties in Carvedilol, Nebivolol -> Preferred for heart failure treatment

Intrinsic Sympathomimetic Activity

• Agents: Pindolol, Acebutolol
• Mechanism: Weakly stimulate beta-1 and beta-2 receptors -> Diminished effect on cardiac rate/output
• Benefit: Suitable for patients with bradycardia or heart block

Beta-2 Blockers

• No clinically useful beta-2 blockers available

Conclusion

• Adrenergic antagonists are crucial in treating various cardiovascular conditions.
• Understanding their specific actions, uses, and side effects is key for effective clinical application.