CVS

• Cardiac glycosides are the oldest drugs still used
• Cardiac glycosides can be obtained from plant sources such as Digitalis leaves (from Wooly foxglove and Wild purple foxglove) and Strophanthus seeds
• Cardiac glycosides have absolute structural requirements including an OH group at C3 and C14, unsaturated lactone ring at C17, cis fusion of C and D, and sugar at C-3
• Cardiac glycosides have different duration of action based on the number of OH groups present, with Digitoxin lasting 3 weeks, Digoxin lasting 6 days, and Ouabain lasting 1 day
• Cardiac glycosides have different pharmacokinetic properties, with digitoxin having 100% absorption, digoxin 75-85%, and ouabain having insignificant absorption
• Factors affecting the dosage regimen of cardiac glycosides include the level of thyroid hormones in the plasma and plasma potassium concentration
• Cardiac glycosides work by inhibiting Na,K-ATPase to increase intracellular sodium and calcium levels, leading to increased myocardial contractility and decreased heart rate
• Indications for cardiac glycosides include congestive cardiac failure, cardiac arrhythmias, atrial fibrillation, and atrial flutter
• Adverse drug reactions of cardiac glycosides include bradycardia, extrasystoles, paroxysmal atrial tachycardia, paroxysmal ventricular tachycardia, nausea/vomiting, anorexia, fatigue, weakness, visual disturbances, and gynecomastia
• Toxicity symptoms of cardiac glycosides include extrasystoles, tachycardia, fibrillation, AV block, nausea, vomiting, ECG changes, and alterations in PR interval, QRS complex, and T wave
• Treatment for cardiac glycoside toxicity includes withdrawal, proper antiarrhythmics, potassium salts in the absence of renal failure, and Cg antibodies
• Drug interactions with cardiac glycosides include synergism with diuretics, antagonism with potassium, additive/antagonism with sympathomimetics, antagonism with antacids, antagonism with cholestyramine, and additive effect with calcium
• Antiarrhythmic drugs work by inhibiting the spread and discharge of impulses in the heart to treat arrhythmias
• Causes of arrhythmias include altered normal automaticity, ectopic foci formation, damage of cardiac muscle leading to excitability, and change in impulse conduction
• Types of cardiac arrhythmias include tachycardia (supraventricular and ventricular), bradycardia, partial AV block, and complete AV block
• Objectives of antiarrhythmic drugs include inhibiting the spread of impulses and suppressing the discharge of impulses in the heart
• Mechanisms of antiarrhythmics involve blocking Na channels, β adrenoceptors, K channels at repolarized state, Ca channels, and opening K channels at depolarized state
• Classes of antiarrhythmics include Class I (Na channel blockers), Class II (β adrenoceptor blockers), Class III (K channel blockers at repolarized state), and Class IV (Ca channel blockers)
• Class I antiarrhythmics are further classified into Class Ia, Ib, and Ic based on their rate of association/dissociation kinetics and effects on action potential duration
• Quinidine is a Class I antiarrhythmic obtained from Cinchona bark, with actions including blocking K channels, increasing action potential duration, widening QRS complex, and shifting membrane responsiveness
• Quinidine effects:

  • Increases APD
  • Shifts membrane responsiveness to the right
  • Widens QRS complex due to excessive depolarization of the ventricles
• Quinidine antiarrhythmic actions:

  • Low dose: increases AV conduction, decreases PR interval
  • High dose: decreases AV conduction, increases PR interval
• Quinidine extracardiac actions:

  • Antimalarial properties similar to quinine
  • Antipyretic properties similar to quinine
  • Curaromimetic action, blocks nicotinic receptor at NMJ like T.curarine
  • Atropine-like action, blocks muscarinic receptors, vagolytic and sympatholytic
  • Acts as a local anesthetic by blocking sodium channels on nerves
  • Alpha blockade, specifically alpha-1, resulting in hypotension
• Quinidine indications:

  • Atrial fibrillation
  • Atrial flutter
  • Paroxysmal tachycardia
  • Ventricular tachycardia
  • Extrasystoles
• Quinidine adverse drug reactions:

  • Cinchonism symptoms like NVD, Genitis, Vertigo, Headache
  • Hypotension by blocking alpha-1 receptor
  • Heart block by blocking AV node
  • Atrial embolism by reducing atrial contractility
  • Arrhythmias, specifically bradyarrhythmia
  • Hypersensitivity reactions, type-1 reaction
  • Contraindications: heart failure, complete AV block, atrial thrombosis
• Quinidine signs/symptoms of toxicity:

  • Widened QRS complex
  • Increased QT interval
  • Increased PR interval
  • Cinchonism symptoms
• Lidocaine (Class 1B) effects:

  • Given intravenously
  • Rapid onset and short duration, used in emergencies
  • Less hypotension, used in myocardial infarction
  • No change in ERP in the atrium, not used in atrial arrhythmias, specifically for ventricular arrhythmias
  • Lacks vagolytic action, no change in AV conduction
• Phenytoin:

  • Anticonvulsant
  • Not commonly used
  • Tocainide and mexilitine are congeners of lidocaine
  • Orally effective
  • Used in ventricular arrhythmias
• Propafenone:

  • Orally effective
  • Similar to flecainide, no vagolytic action, used in ventricular arrhythmias
  • Moricizine has the same effects as propafenone and flecainide, but is a Phenothiazine derivative
• Sotalol (Class 2):

  • Non-selective beta-blocker
  • Blocks Na channel
  • Blocks K channel, increasing RP and APD
• Amiodarone (Class III):

  • Orally effective
  • Long half-life (13-103 days)
  • Blocks K channel, increases refractory period
  • Blocks Na channel in inactivated state
  • Blocks beta receptors weakly
  • Blocks Ca channel
  • Used in both supra-ventricular and ventricular arrhythmias
• Verapamil (Class IV):

  • Calcium channel blocker
  • Used for "static arrhythmia"
  • Blocks both activated and inactivated Ca channels
  • More effective on tissues that fire frequently, used in re-entrant supra-ventricular tachycardia
• Nicorandil:

  • Increases K conductance
  • Used in paroxysmal ventricular tachycardia
• Ischemic heart disease:

  • Inadequate blood flow to myocardium through coronary circulation
  • Results from an imbalance between O2 requirements and O2 supply
• Types of angina:

  • Classic/effort/exertional/chronic stable/predictable angina: due to atherosclerosis, increased O2 demand
  • Variant/prinzmetal/spontaneous/rest/angiospastic/vasospastic/unstable angina: due to spasmodic occlusion of large coronary artery, reduced O2 supply
• Therapeutic objectives:

  • Classic angina: decrease O2 demand, prevent atherosclerosis
  • Variant angina: increase O2 supply
• Mechanisms to decrease oxygen demand:

  • Depress myocardium
  • Block Ca channel for less contractility and HR
  • Open K channel for indirect Ca inhibition
  • Dilate peripheral vessels for less preload and demand
• Mechanisms to increase oxygen supply:

  • Dilate coronary vessels
  • Block Ca channel for direct smooth muscle relaxation
  • Open K channel
• Classes of anti-anginal drugs:

  • Coronary vasodilators: nitrites (nitroglycerin), Ca channel blockers (diltiazem), K channel openers (nicorandil)
  • Peripheral vasodilators: nitrites (nitroglycerin), Ca channel blockers (nifedipine), K channel openers (nicorandil)
• Classes of anti-anginal drugs (cont.):

  • Myocardial depressants: Ca channel blockers (verapamil), beta receptor blockers (sotalol), K channel openers (nicorandil)
  • Lipid-lowering drugs