Cardiac Arrhythmias and Antiarrhythmic Drugs

Cardiac Arrhythmias

• Cardiac arrhythmias are abnormalities in the heart's rate, regularity, or the origin of its impulses.
• These abnormalities can cause the heart to beat too fast (tachycardia), too slow (bradycardia), or irregularly.
• Examples of cardiac arrhythmias include supraventricular and ventricular arrhythmias.

Vaughan Williams Classification of Antiarrhythmic Drugs

• Class I drugs are Sodium (Na+) Channel Blockers that reduce heart excitability by blocking fast Na+ channels.
• Class IA drugs like Quinidine, Procainamide, and Disopyramide slow phase 0 depolarization and prolong repolarization.
• Class IB drugs like Lidocaine and Mexiletine shorten repolarization.
• Class IC drugs like Flecainide and Propafenone markedly slow phase 0 depolarization.
• Class II drugs are Beta-Adrenergic Blockers (β-Blockers) that reduce sympathetic activity on the heart.
• Propranolol, Metoprolol and Esmolol are examples of beta-blockers, which decrease heart rate and contractility.
• Class III drugs are Potassium (K+) Channel Blockers that prolong repolarization by blocking K+ channels.
• Amiodarone, Sotalol, and Dofetilide are examples of Class III drugs that increase the effective refractory period.
• Class IV drugs are Calcium (Ca2+) Channel Blockers that slow conduction in the SA and AV nodes by blocking L-type Ca2+ channels.
• Examples of Class IV drugs include Verapamil and Diltiazem.

Other Antiarrhythmic Agents

• Adenosine activates adenosine receptors, increasing K+ efflux and hyperpolarizing cells, which slows AV node conduction.
• Digoxin increases vagal tone and reduces sympathetic activity, slowing AV node conduction.

Clinical Use of Antiarrhythmic Drugs

• Adenosine, Verapamil, Diltiazem and Beta-blockers can be used for Supraventricular Tachycardia (SVT).
• Atrial Fibrillation/Flutter can be treated with Amiodarone, Dofetilide, Beta-blockers, Diltiazem and Digoxin.
• Ventricular Tachycardia can be treated with Amiodarone, Lidocaine and Beta-blockers.

Adverse Effects of Antiarrhythmic Drugs

• Class I drugs can have proarrhythmic effects and cause QT prolongation.
• Class II drugs can cause bradycardia, hypotension and bronchospasm.
• Class III drugs can cause QT prolongation (Torsades de Pointes) and thyroid abnormalities (Amiodarone induced).
• Class IV drugs can cause bradycardia, AV block and constipation.

Heart Failure

• Heart Failure is a chronic condition where the heart muscle cannot pump enough blood to meet the body's needs.

Drug Classes for Heart Failure

• ACE Inhibitors/ARBs block the renin-angiotensin-aldosterone system (RAAS), reducing preload and afterload, to prevent cardiac remodeling.
• Enalapril and Lisinopril are ACE Inhibitors, while Losartan and Valsartan are ARBs.
• Beta-Blockers block the sympathetic nervous system effects, reducing heart rate and blood pressure and preventing remodeling.
• Examples of Beta-Blockers are Metoprolol, Carvedilol and Bisoprolol.
• Diuretics increase urine production to reduce fluid volume, reducing preload and symptoms of congestion.
• Furosemide is a Loop diuretic, Hydrochlorothiazide is a Thiazide diuretic and Spironolactone is an Aldosterone antagonist.
• Digoxin inhibits the Na+/K+ ATPase pump, increasing cardiac contractility and reducing heart rate.
• Vasodilators: Hydralazine dilates arterioles (reducing afterload), and isosorbide dinitrate dilates venules (reducing preload).
• Inotropes like Dobutamine and Milrinone increase cardiac contractility and improve cardiac output in acute heart failure.

Clinical Use in Heart Failure

• First-line Therapies include ACE inhibitors/ARBs, Beta-blockers and Diuretics.
• Additional therapies include Digoxin and Hydralazine/Isosorbide dinitrate.
• Inotropes (Dobutamine, Milrinone) are used in acute heart failure.

Adverse Effects of Heart Failure Drugs

• ACE Inhibitors/ARBs can cause hypotension, hyperkalemia, cough (ACE Inhibitors) and angioedema.
• Beta-Blockers can cause bradycardia, hypotension and fatigue.
• Diuretics can cause electrolyte imbalances, dehydration and hypotension.
• Digoxin can cause arrhythmias, nausea and visual disturbances.

Hypertension

• Hypertension is defined as persistently high blood pressure, typically ≥130/80 mm Hg.

Drug Classes for Hypertension

• Diuretics reduce blood volume by increasing urine output.
  • Thiazide Diuretics (Hydrochlorothiazide) act on the distal convoluted tubule.
  • Loop Diuretics (Furosemide) act on the Loop of Henle.
  • Potassium-Sparing Diuretics (Spironolactone) act on the Collecting Duct.
• ACE Inhibitors/ARBs block the RAAS system, lowering blood pressure and providing renal protection.
  • Enalapril and Lisinopril are ACE Inhibitors.
  • Losartan and Valsartan are ARBs.
• Calcium Channel Blockers (CCBs) block calcium channels in blood vessels and the heart.
  • Dihydropyridines (Amlodipine, Nifedipine) cause vasodilation.
  • Non-dihydropyridines (Verapamil, Diltiazem) reduce heart rate and contractility.
• Beta-Blockers block the effects of adrenaline, lowering the heart rate and blood pressure.
  • Examples include Metoprolol, Atenolol and Propranolol.
• Alpha-Blockers block alpha-adrenergic receptors, relaxing blood vessels (e.g., Prazosin, Terazosin).
• Central Alpha-Agonists reduce sympathetic outflow from the CNS (e.g., Clonidine, Methyldopa).
• Vasodilators like Hydralazine and Minoxidil directly relax vascular smooth muscle, decreasing systemic vascular resistance.

Clinical Use in Hypertension

• First-line Therapies include Thiazide diuretics, ACE inhibitors/ARBs, CCBs and Beta-blockers.
• Compelling indications include specific conditions (e.g., diabetes, kidney disease) that guide the choice of drug.

Adverse Effects of Hypertension Drugs

• Diuretics can cause electrolyte imbalances and dehydration.
• ACE Inhibitors/ARBs can cause hypotension, hyperkalemia, cough (ACE Inhibitors) and angioedema.
• CCBs can cause hypotension, peripheral edema and bradycardia (Non-dihydropyridines).
• Beta-Blockers can cause bradycardia, fatigue and bronchospasm.
• Alpha-Blockers can cause postural hypotension.
• Central Alpha-Agonists can cause sedation and dry mouth.
• Vasodilators can cause reflex tachycardia, sodium and water retention.

Angina Pectoris

• Angina Pectoris is chest pain or discomfort caused by reduced blood flow to the heart muscle.

Drug Classes for Angina

• Nitrates convert to nitric oxide (NO), causing vasodilation, which reduces preload and afterload, and dilates coronary arteries (e.g., Nitroglycerin, Isosorbide dinitrate).
• Beta-Blockers reduce heart rate and contractility, decreasing myocardial oxygen demand (e.g., Metoprolol, Atenolol).
• Calcium Channel Blockers (CCBs) block calcium channels in blood vessels, reducing blood pressure and myocardial contractility.
  • Dihydropyridines (Amlodipine, Nifedipine) cause vasodilation.
  • Non-dihydropyridines (Verapamil, Diltiazem) reduce heart rate and contractility.
• Ranolazine inhibits late sodium current in cardiac cells, reducing myocardial oxygen demand without affecting heart rate or blood pressure.

Clinical Use in Angina

• Nitroglycerin is used for acute angina.
• Beta-blockers, CCBs, Long-acting nitrates and Ranolazine are used for chronic angina.

Adverse Effects of Angina Drugs

• Nitrates can cause headache, hypotension and reflex tachycardia.
• Beta-Blockers can cause bradycardia, hypotension and fatigue.
• CCBs can cause hypotension, peripheral edema and bradycardia (Non-dihydropyridines).
• Ranolazine can cause QT prolongation, dizziness and constipation.

Hyperlipidemia

• Hyperlipidemia is high levels of lipids (fats) in the blood, including cholesterol and triglycerides.

Drug Classes for Hyperlipidemia

• Statins (HMG-CoA Reductase Inhibitors) inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis.
  • Statins lower LDL cholesterol, raise HDL cholesterol and lower triglycerides (e.g., Atorvastatin, Simvastatin, Rosuvastatin).
• Bile Acid Sequestrants bind bile acids in the intestine, preventing their reabsorption, leading to lower LDL cholesterol (e.g., Cholestyramine, Colesevelam).
• Niacin (Nicotinic Acid) inhibits lipolysis in adipose tissue, reducing the production of free fatty acids.
  • Niacin lowers LDL cholesterol and triglycerides, and raises HDL cholesterol.
• Fibrates activate PPAR-alpha, increasing the synthesis of lipoprotein lipase, thus lowering triglycerides and raising HDL cholesterol (e.g., Gemfibrozil, Fenofibrate).
• Cholesterol Absorption Inhibitor (Ezetimibe) inhibits the absorption of cholesterol in the small intestine, which lowers LDL cholesterol.
• PCSK9 Inhibitors are monoclonal antibodies that inhibit PCSK9, increasing the number of LDL receptors, significantly lowering LDL cholesterol (e.g., Alirocumab, Evolocumab).
• Omega-3 Fatty Acids reduce triglyceride synthesis, lowering triglycerides.

Clinical Use in Hyperlipidemia

• Statins are the first-line therapy for LDL cholesterol reduction.
• Combination therapy is used when single agents are insufficient.
• Specific lipid profiles guide drug choices depending on the conditions.

Adverse Effects of Hyperlipidemia Drugs

• Statins can cause myopathy and liver dysfunction.
• Bile Acid Sequestrants can cause GI distress and reduce the absorption of other drugs.
• Niacin can cause flushing, hyperglycemia and hepatotoxicity.
• Fibrates can cause myopathy and gallstones.
• Ezetimibe is well-tolerated but rarely causes liver dysfunction.
• PCSK9 Inhibitors can cause injection site reactions and nasopharyngitis.
• Omega-3 Fatty Acids can cause fishy aftertaste and GI upset.