Antidysrhythmic, Coagulation, and Anti-lipemic Drugs Overview

Antidysrhythmic Drugs

• Antiarrhythmic drugs treat irregular heartbeats (arrhythmias) like atrial fibrillation, ventricular tachycardia, and atrial flutter.
• They alter the heart's electrical activity to restore normal rhythm.
• Vaughan-Williams classification groups antiarrhythmics into four classes based on mechanisms of action.

Class I: Sodium Channel Blockers

• Class I-A: (Quinidine, Procainamide, Disopyramide)
  • Moderately block sodium channels during depolarization.
  • Slows electrical conduction.
  • Prolongs action potential and refractory period.
  • Blocks potassium channels, prolonging repolarization and increasing QT interval.
  • Treats atrial and ventricular arrhythmias.
  • Risks include QT interval prolongation and torsades de pointes.
• Class I-B: (Lidocaine, Mexiletine)
  • Bind to sodium channels primarily during depolarization to stabilize membranes.
  • Shortens action potential and decreases refractory period.
  • Primarily affects ischemic or depolarized tissue.
  • Effective treatment for ventricular arrhythmias, particularly after heart attacks.
  • Usually administered intravenously in acute settings.
• Class I-C: (Flecainide, Propafenone)
  • Strongly block sodium channels during depolarization, slowing conduction.
  • Little effect on action potential duration, but increases refractory period.
  • Used for atrial and ventricular arrhythmias, especially supraventricular ones.
  • Risk of proarrhythmia (inducing new arrhythmias), particularly in structurally abnormal hearts.

Class II: Beta-Adrenergic Blockers

• Block sympathetic stimulation (norepinephrine and epinephrine) on beta-1 adrenergic receptors.
• Examples: Propranolol, Metoprolol, Atenolol, Esmolol.
• Block beta-1 receptors, reducing heart rate and contractility.
• Decrease automaticity and slow conduction through the AV node.
• Increase AV node refractory period, preventing rapid atrial impulses from reaching ventricles.
• Used to treat atrial fibrillation, atrial flutter, and ventricular arrhythmias.
• Used for rate control in supraventricular arrhythmias and post-myocardial infarction.

Class III: Potassium Channel Blockers

• Block potassium channels, prolonging repolarization and increasing refractory period.
• Effective for arrhythmias involving abnormal repolarization.
• Examples: Amiodarone, Sotalol, Dofetilide, Ibutilide.
• Block potassium channels (delayed rectifier potassium channels), prolonging action potential and refractory periods.
• Prevents reentry circuits and stabilizes heart rhythm.
• Amiodarone possesses Class I, II, and IV properties.
• Effective for supraventricular and ventricular arrhythmias (atrial fibrillation, tachycardia, fibrillation).
• Risks include QT interval prolongation and torsades de pointes.

Class IV: Calcium Channel Blockers

• Block L-type calcium channels in SA node, AV node, and myocardium.
• Examples: Verapamil, Diltiazem.
• Block L-type calcium channels, decreasing intracellular calcium.
• Slows depolarization and conduction velocity.
• Decrease automaticity in SA node and slow conduction in AV node.
• Used for supraventricular arrhythmias (atrial fibrillation, flutter), controlling rate and blocking rapid atrial impulses.
• Also used for paroxysmal supraventricular tachycardia (PSVT).

Other Antiarrhythmic Drugs

• Adenosine: Activates A1 adenosine receptors, hyperpolarizing the heart and decreasing AV node conduction.
  • Acute termination of supraventricular tachycardia (SVT), especially reentrant arrhythmias.
• Digoxin: Cardiac glycoside inhibiting Na+/K+ ATPase, increasing intracellular calcium and slowing AV node conduction, increasing contractility.
  • Rate control for atrial fibrillation and atrial flutter; also for heart failure.

Coagulation Modifier Drugs

• Treat blood clotting disorders (DVT, PE, AF) and prevent clots after surgeries.

Anticoagulants

• Heparins: (Unfractionated heparin (UFH), Low-molecular-weight heparins (LMWHs) - Enoxaparin, Dalteparin)
  • UFH binds to antithrombin III, enhancing its activity to inactivate thrombin and factor Xa, preventing fibrin formation.
  • LMWHs primarily inhibit factor Xa.
  • Used for acute anticoagulation (DVT, PE, ACS) and surgical prophylaxis.
  • UFH usually administered intravenously, LMWHs subcutaneously.
• Vitamin K Antagonists: (e.g., Warfarin)
  • Inhibits vitamin K, essential for synthesizing clotting factors (II, VII, IX, X, proteins C and S).
  • Used for long-term anticoagulation (AF, DVT, PE).
  • Requires regular INR monitoring.
• Direct Oral Anticoagulants (DOACs): (e.g., Apixaban, Rivaroxaban, Edoxaban, Dabigatran)
  • Direct Factor Xa Inhibitors (Apixaban, Rivaroxaban, Edoxaban): Inhibits factor Xa, blocking thrombin formation.
  • Direct Thrombin Inhibitor (Dabigatran): Inhibits thrombin, blocking fibrinogen conversion.
  • Used for stroke prevention in AF, DVT, PE, and post-hip/knee surgery.
  • More convenient than warfarin, no routine monitoring.

Antiplatelet Drugs

• Aspirin: Irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 and platelet aggregation.
  • Secondary prevention of MI, stroke, and cardiovascular events.
  • Primary prevention for high-risk patients.
• P2Y12 Inhibitors: (Clopidogrel, Prasugrel, Ticagrelor)
  • Block P2Y12 receptors, preventing ADP-mediated platelet activation.
  • Used in ACS, PCI, and prevention of stent thrombosis.
• Glycoprotein IIb/IIIa Inhibitors: (Abciximab, Eptifibatide, Tirofiban)
  • Block GPIIb/IIIa receptors, preventing platelet aggregation.
  • Used for acute coronary syndromes, PCI.

Thrombolytics (Fibrinolytics)

• Break down existing clots by enhancing plasminogen activation to plasmin.
• Examples: tPA (Tissue Plasminogen Activator), Alteplase, Reteplase, Tenecteplase.
  • Activate plasminogen, creating plasmin to dissolve fibrin.
  • Used in emergency situations for dissolving thrombi (MI, ischemic stroke, PE).

Antifibrinolytics

• Inhibit fibrin breakdown and prevent excessive bleeding.
• Examples: Tranexamic Acid, Aminocaproic Acid.
  • Inhibit plasminogen activation, preventing plasmin formation.
  • Used for preventing and treating bleeding disorders and excessive bleeding.

Antilipemic Drugs

• Manage elevated lipids (cholesterol and triglycerides), combating cardiovascular diseases (atherosclerosis, CAD, stroke).

• Statins: (HMG-CoA Reductase Inhibitors) - Atorvastatin, Simvastatin, Rosuvastatin, Pravastatin

  • Inhibit HMG-CoA reductase, decreasing cholesterol synthesis and increasing LDL receptor expression in liver.
  • Lower LDL, VLDL and triglycerides; modest effect on HDL.
  • Most effective for lowering LDL, reduces cardiovascular events.

• Bile Acid Sequestrants: (Resins) - Cholestyramine, Colestipol, Colesevelam

  • Bind bile acids in intestine, preventing reabsorption, forcing liver to use cholesterol to produce more bile.
  • Primarily lower LDL cholesterol, may increase triglycerides.
  • Often used with statins for enhanced lipid-lowering.

• Fibrates: (Fibric Acid Derivatives) - Gemfibrozil, Fenofibrate

  • Activate PPAR-α, increasing lipoprotein lipase, decreasing VLDL and apolipoprotein C-III, and increasing HDL.
  • Primarily lower triglycerides, modestly lower LDL, increase HDL.

• Nicotinic Acid (Niacin):

  • Inhibits lipolysis in adipose tissue, reducing free fatty acid release, lower triglyceride synthesis.
  • Reduces VLDL production, lowers LDL, increases HDL.
  • Effective at reducing triglycerides and LDL, and raising HDL. Side effects at high doses.

• Cholesterol Absorption Inhibitors: (e.g., Ezetimibe)

  • Inhibit NPC1L1 protein, reducing cholesterol absorption.
  • Lower LDL cholesterol.
  • Often used with statins.

• PCSK9 Inhibitors: (Alirocumab, Evolocumab)

  • Inhibit PCSK9, increasing LDL receptor availability and cholesterol clearance.
  • Significantly lower LDL cholesterol, especially useful in familial hypercholesterolemia or statin intolerance.

• Omega-3 Fatty Acids: (Fish oil, EPA and DHA, Icosapent ethyl)

  • Reduce hepatic triglyceride synthesis, increase lipoprotein lipase activity.
  • Primarily lower triglycerides, modest effect on LDL.

Explore the mechanisms and classifications of antiarrhythmic drugs with this quiz. Test your knowledge of Class I-A, I-B, and I-C drugs as well as their effects and risks. Understand the Vaughan-Williams classification system and its significance in cardiology.