Pharmacology: Class I-C Drugs Effects

Antidysrhythmic Drugs

• Antiarrhythmic drugs treat irregular heartbeats (arrhythmias), such as atrial fibrillation, ventricular tachycardia, and atrial flutter.
• They work by modifying the heart's electrical activity to restore normal rhythm.
• The Vaughan-Williams classification system groups antiarrhythmic drugs into four classes based on their mechanism of action.

Class I: Sodium Channel Blockers

• These drugs block sodium channels during the action potential, slowing depolarization and sometimes conduction.
• Class I-A (e.g., Quinidine, Procainamide, Disopyramide): Moderately block sodium channels during depolarization, prolonging action potential and increasing the refractory period. They also block potassium channels, prolonging repolarization and increasing the QT interval; risk of torsades de pointes.
• Class I-B (e.g., Lidocaine, Mexiletine): Primarily bind to sodium channels during the depolarized state, shortening action potential duration and decreasing the refractory period; preferentially affect ischemic or depolarized tissue, used for ventricular arrhythmias, particularly after a heart attack.
• Class I-C (e.g., Flecainide, Propafenone): Strongly block sodium channels during depolarization, significantly slowing conduction velocity; have little effect on action potential duration but increase the refractory period; used for both atrial and ventricular arrhythmias, especially supraventricular arrhythmias.

Class II: Beta-Adrenergic Blockers

• These drugs block the effects of sympathetic stimulation on the heart, particularly at beta-1 adrenergic receptors.
• Examples include Propranolol, Metoprolol, Atenolol, Esmolol.
• Mechanism of Action: Block beta-1 adrenergic receptors to reduce heart rate and contractility, decrease automaticity, and slow conduction through the atrioventricular (AV) node.
• They increase the refractory period of the AV node and are used to treat atrial fibrillation, atrial flutter, and ventricular arrhythmias to control rate in supraventricular arrhythmias and post-myocardial infarction.

Class III: Potassium Channel Blockers

• These drugs block potassium channels, prolonging repolarization and increasing the refractory period.
• Examples include Amiodarone, Sotalol, Dofetilide, Ibutilide.
• Mechanism of Action: Block potassium channels (specifically delayed rectifier potassium channels). This prolongs the action potential duration and the refractory period. This effect prevents reentry circuits, thereby stabilizing the heart's rhythm.
• Effect: Effective for both supraventricular and ventricular arrhythmias, including atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. Potentially increases QT interval, increasing risk of torsades de pointes.

Class IV: Calcium Channel Blockers

• These drugs block L-type calcium channels in the SA node, AV node, and myocardium, slowing the rate of depolarization and conduction velocity.
• Examples include Verapamil, Diltiazem.
• Mechanism of Action: Block L-type calcium channels, decreasing intracellular calcium. This slows the rate of depolarization and conduction velocity.
• Effect: Effective in supraventricular arrhythmias such as atrial fibrillation and atrial flutter, controlling rate to prevent rapid atrial impulses from reaching the ventricles. Also used to manage paroxysmal supraventricular tachycardia.

Other Antiarrhythmic Drugs

• These drugs don't fit neatly into the Vaughan-Williams classification, but remain important in management.
• Adenosine: Activates A1 adenosine receptors in the heart, hyperpolarizing and decreasing conduction through the AV node. This block can reset the heart's rhythm and is primarily used for acute termination of SVT (supraventricular tachycardia), especially reentrant arrhythmias involving the AV node.
• Digoxin: Inhibits the Na+/K+ ATPase pump, increasing intracellular calcium; increases contractility and slows conduction through AV node. Used for rate control in atrial fibrillation and atrial flutter. Used in heart failure.

Coagulation Modifier Drugs

• Coagulation modifier drugs manage conditions related to blood clotting, for example, deep vein thrombosis (DVT), pulmonary embolism (PE).
• Anticoagulants: Prevent clot formation; examples include Heparins (unfractionated and low molecular weight) and Vitamin K antagonists (e.g., warfarin). Unfractionated Heparin binds to antithrombin III, enhancing its activity. Low Molecular Weight Heparins primarily inhibit factor Xa. Warfarin inhibits vitamin K-dependent clotting factors (II, VII, IX, X); prevents activation of these clotting factors, thereby reducing clot formation.
• Administration and Monitoring: Administration varies depending on type of anticoagulant; monitoring (e.g., INR) is important for some drugs to adjust dosage and maintain therapeutic levels.
• Direct Oral Anticoagulants (DOACs): Directly inhibit factor Xa, or thrombin; examples include Apixaban, Rivaroxaban, Edoxaban, Dabigatran.

Antiplatelet Drugs

• Antiplatelet drugs inhibit platelet aggregation, preventing clot formation.
• Aspirin (Acetylsalicylic Acid): Irreversibly inhibits cyclooxygenase-1 (COX-1); reduces thromboxane A2 (TXA2) production, reducing platelet aggregation.
• P2Y12 Inhibitors (e.g., Clopidogrel, Prasugrel, Ticagrelor): Block P2Y12 receptors on platelets, which are involved in platelet aggregation.
• Glycoprotein IIb/Illa Inhibitors (e.g., Abciximab, Eptifibatide, Tirofiban): Block GPIIb/IIIa receptors, preventing platelet aggregation and fibrinogen binding.

Thrombolytic (Fibrinolytic) Drugs

• Thrombolytic drugs break down existing clots by activating plasminogen, which converts to plasmin. The enzyme, plasmin, degrades fibrin. Examples: tPA (Tissue Plasminogen Activator), Alteplase, Reteplase, Tenecteplase.
• Effect: Used in emergency situations for acute myocardial infarction (MI), acute ischemic stroke, and pulmonary embolism (PE).

Antilipemic Drugs (Lipid-Lowering Drugs)

• Statins (HMG-CoA Reductase Inhibitors): Inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver. Examples include Atorvastatin, Simvastatin, Rosuvastatin, and Pravastatin. 
• Bile Acid Sequestrants (Resins): Bind to bile acids in the intestines, preventing their reabsorption and increasing cholesterol excretion. Examples include Cholestyramine, Colestipol, and Colesevelam.
• Fibrates (Fibric Acid Derivatives): Activate peroxisome proliferator-activated receptor alpha (PPAR-α); affects lipid metabolism. Increase lipoprotein lipase activity, and decrease apolipoprotein C-III synthesis to increase triglyceride breakdown; Examples include Gemfibrozil and Fenofibrate.
• Nicotinic Acid (Niacin): Inhibits lipolysis; lowers triglycerides and increases HDL cholesterol.
• Cholesterol Absorption Inhibitors: Inhibit certain intestinal proteins (e.g., NPC1L1) that absorb dietary cholesterol, reducing cholesterol absorption. Examples include Ezetimibe.
• PCSK9 Inhibitors: Newer biologic agents that bind to PCSK9, preventing its interaction with LDL receptors. Examples include Alirocumab, and Evolocumab.
• Omega-3 Fatty Acids: Decrease hepatic synthesis of triglycerides, increasing lipoprotein lipase activity. Examples include Fish oil (EPA and DHA), Icosapent ethyl.

This quiz explores the primary effects of Class I-C antiarrhythmic drugs on the heart. Test your understanding of how these medications influence cardiac function and their mechanisms of action in treating arrhythmias.