2.02 - Kinetics & Dynamics Of Commonly Used Cardiac Drugs Flashcards
What are the four classes of antiarrhythmic drugs?
Class I: voltage sensitive sodium blockers
Class II: beta-adrenoreceptor antagonists
Class III: prolong cardiac action potential
Class IV: calcium antagonists
Other unclassified drugs
Describe the action of Class I Antiarrhythmics and provide examples
Class I split in to Class Ia, Ib & Ic
All Class I drugs inhibit phase 0 (upstroke) and therefore decrease conduction velocity
They also prolong repolarisation - increased the effective refractory period
Examples: Quinidine (Ia), Lidocaine (Ib) and Flecainide (Ic)
Describe Class II Antiarrhythmics
Beta-blockers. Inhibit sympathetic input on the pacing of the heart by blocking beta1 adrenoceptors
Used most commonly for supraventricular and ventricular arrhythmias caused by sympathetic stimulation
Side effects: bronchospasm, cold extremities, impotence (due to beta2 blockade). Excessage negative inotropic effect –> heart block, bradycardia (excessive beta1 blockade). Insomnia, depression.
Describe Class III Antiarrhythmics
Inhibit K+ channels (inhibit repolarisation)
Increase the duration of Phase II (plateau) –> prolonged repolarisation
Example: Ibutilide
Describe Class IV Antiarrhythmics
Act preferentially on SA and AV nodes.
Slow action potential upstroke - slows conduction velocity through AV node
Example: Verapamil (more effective on calcium currents in cardiac tissue)
What classes of drugs are used in the treatment of Heart Failure
Positive inotropic drugs: cardiac glycosides, phosphodiesterase inhibitors, beta-adrenoreceptor agonists
Drugs acting on non-cardiac targets: diuretics, ACE inhibitors, AT1R antagonists, beta-adrenceptor antagonists
Describe the Cardiac Glycosides and provide an example
Example: Digoxin
Inhibit Na/K ATPase –> relative reduction of calcium expulsion –> increased contractility
Narrow therapeutic window
Other drugs and disease states can increase the plasma concentrations of Digoxin (chronic renal failure, antibiotics, verapamil)
Describe Beta-Adrenceptor Agonists in the treatment of heart failure and provide examples
E.g. Dobutamine
Positive inotropic and chronotropic effects. Beta1 stimulation increases adenylyl cyclase activity –> increased cAMP –> activation of PKA –> opening of calcium channels –> increaseing calcium levels –> increased contractility
Describe the Phosphodiesterase Inhibitors in the treatment of heart failure
Amrinone, Milrinone
Block the breakdown of cAMP by phosphodiesterase –> increased PKA –> increased calcium levels –> increased contractility
Describe the ACE Inhibitors in the treatment of heart failure
Captopril, Enalapril
Block the formation of AngII (prevent vasocontriction, water retention, hypertrophy/hyperplasia)
Describe the effect of spironolactone in the treatment of heart failure
Competitive antagonist of mineralocorticoid receptor in the kidneys –> prevent action of aldosterone –> decreased ENaC expression in collecting tubules –> decreased Na reabsorption –> decreased water reabsorption
Describe the action of Beta-Blockers in the treatment of heart failure
Propranolol, carvedilol.
May seem counterintuitive due to negative inotropic effect.
But inhibit the sympathetic nervous system compensation and also inhibit renin release
What classes of drugs are used in the treatmentof Angina?
Vasodilators: organic nitrates, calcium channel blockers
Non-vasodilators: beta blockers
Describe the effect of organic nitrates in the threatment of Angina
Nitroglycerin
Converted to NO (active form) –> increased cGMP in VSMCs –> decreased intracellular calcium –> vasodilation
Very high first pass effect, so given sublingually. Short duration of action (15-30min)
Describe the use of Calcium Channel bockers in the treatment of Angina
Verapamil (cardiac), Nifedipine (vascular)
Block the inward movement of Calcium.
Active on smooth muscles (vasodilation) and cariac muscles (reduce oxygen requirement)
