Autonomic Drugs in Cardiovascular Disease

ANS & CV Physiology - Heart's Command Central

• Sympathetic (SNS) - "Fight/Flight":
  • Effects: ↑ Heart Rate (HR), ↑ Contractility, Vasoconstriction (most vessels) → ↑ Blood Pressure (BP).
  • Key Receptors & Effects:
    • $\beta_1$ (Heart): ↑ HR, ↑ Contractility, ↑ Atrioventricular (AV) conduction.
    • $\alpha_1$ (Blood Vessels): Vasoconstriction → ↑ Peripheral Resistance, ↑ BP.
    • $\beta_2$ (Blood Vessels - e.g., skeletal muscle, coronary): Vasodilation.
• Parasympathetic (PNS) - "Rest/Digest":
  • Effects: ↓ HR, ↓ Atrial Contractility, ↓ AV conduction.
  • Key Receptors & Effects:
    • $M_2$ (Heart): ↓ HR, ↓ AV conduction.
• Neurotransmitters: SNS: Norepinephrine (NE), Epinephrine (Epi); PNS: Acetylcholine (ACh).


⭐ Bezold-Jarisch reflex (BJR): ventricular sensor stimulation (e.g., inferior MI, certain toxins) → triad of hypotension, bradycardia, and apnea.

Beta-Blockers in CVD - Brady Bunch Beats

Mechanism: Block β-receptors → ↓Heart Rate (HR), ↓Contractility, ↓Renin. Use: Hypertension (HTN), Angina, Post-Myocardial Infarction (Post-MI), Heart Failure (HF), Arrhythmias.

Classification & Key Examples:

• Post-MI: Metoprolol, Atenolol, Carvedilol.
• HF (stable systolic): Carvedilol, Bisoprolol, Metoprolol Succinate (XL).
• Arrhythmias (rate control): Metoprolol, Esmolol (SVT).

Side Effects (📌 ABCDE):

• Asthma exacerbation
• Bradycardia, Bronchospasm, Heart Block
• CNS (fatigue), Cold extremities
• Diabetes (mask hypoglycemia), Dyslipidemia
• Erectile dysfunction ⚠️ Withdrawal: Taper dose over 1-2 wks to avoid rebound HTN, angina, arrhythmias.

⭐ For Heart Failure (systolic), Carvedilol, Metoprolol Succinate, and Bisoprolol are key mortality reducers. Start low in stable, euvolemic patients.

Alpha Blockers & Central Sympathoplegics in CVD - Pressure Tamers

• Alpha (α) Blockers: Relax blood vessels.
  • Selective α1 (Prazosin, Terazosin):
    • MOA: Block α1 receptors → vasodilation → ↓Total Peripheral Resistance (TPR).
    • Uses: Hypertension (HTN), especially with Benign Prostatic Hyperplasia (BPH).
    • SE: First-dose hypotension (📌 "Prazosin starts low, goes slow"), postural hypotension, reflex tachycardia.
  • Non-selective α1 & α2 (Phenoxybenzamine, Phentolamine):
    • MOA: Block α1 & α2. Phenoxybenzamine (irreversible), Phentolamine (reversible).
    • Uses: Pheochromocytoma (pre-op/crisis).
    • SE: Significant hypotension, more pronounced reflex tachycardia.
• Central Sympathoplegics: Reduce sympathetic outflow from brain.
  • Clonidine:
    • MOA: CNS α2 agonist → ↓sympathetic outflow.
    • Uses: HTN (not first-line), opioid withdrawal.
    • SE: Sedation, dry mouth, constipation, ⚠️ rebound HTN on abrupt cessation.
  • Methyldopa:
    • MOA: Prodrug → α-methylnorepinephrine (false neurotransmitter) → CNS α2 agonist.
    • Uses: HTN in pregnancy.
    • SE: Sedation, Coombs-positive hemolytic anemia, hepatotoxicity.

⭐ Methyldopa is a preferred antihypertensive agent for managing hypertension during pregnancy due to its established safety profile for both mother and fetus.

Cholinergic Drugs in CVD - Rhythm & Rate Responders

• Muscarinic Antagonists:
  • Atropine:
    • Primary use: Symptomatic bradyarrhythmias, AV block.
    • MOA: Blocks acetylcholine at muscarinic receptors, ↑ heart rate.
    • Key side effects: Tachycardia, dry mouth, blurred vision.
• Cholinesterase Inhibitors (Indirect Cholinomimetics):
  • E.g., Neostigmine, Pyridostigmine.
  • Systemic absorption → CV side effects: Bradycardia, hypotension. (Not primary CV use).
• Direct-Acting Cholinomimetics:
  • E.g., Bethanechol.
  • ⚠️ Contraindicated: Coronary artery disease (CAD), hyperthyroidism, asthma.

  ⭐ Atropine is a competitive antagonist of acetylcholine at muscarinic receptors, effectively treating bradycardia by reducing vagal tone on the SA and AV nodes.

High‑Yield Points - ⚡ Biggest Takeaways

• Beta-blockers (e.g., metoprolol, carvedilol) are cornerstone in heart failure (HF) and post-MI, significantly ↓ mortality.
• ACE inhibitors/ARBs are first-line for hypertension (HTN), HF, and offer renal protection in diabetes.
• Digoxin has a narrow therapeutic index; toxicity is often precipitated by hypokalemia.
• Amiodarone, a broad-spectrum antiarrhythmic, carries notable risks of thyroid dysfunction and pulmonary fibrosis.
• Non-dihydropyridine CCBs (verapamil, diltiazem) are used for rate control in atrial fibrillation and angina.
• Labetalol is a preferred agent for managing hypertensive emergencies during pregnancy due to its safety profile.
• Nitrates provide symptomatic relief in angina via vasodilation; tolerance is a key concern with continuous use.