anti-arrhythmic lecture 1 Flashcards
how many phases does a myocardial action potential have ?
4 phases
phase 0–> upstroke caused by “Na” influx
Phase 1–> K open slightly
Phase 2–> Ca open and K efflux is balanced (leads to platue )
Phase 3–> rapid repolarization
Phase 4 –> rest
How Many phases does pacemaker action potential have ?
3 !
missing phase 1 and 2
Phase 4 –> funny eddy currents start a spontaneous depolarization leading to the threshold
Phase 0 –> “Ca” influx leads to the upstroke and repolarization - slow conduction velocity (ca induced Ca influx ?)
arrythmias can cause the heart to ?
(a) Beat too slowly (bradycardia)
(b) Beat too rapidly (tachycardia)
(c) Beat regularly (sinus tachycardia or sinus bradycardia)
(d) Beat irregularly (atrial fibrillation
common causes of arrhythmia
Common causes of arrhythmias:\
•Abnormal automaticity •Re-entrant circuits •Afterdepolarizations •Accessory tract pathways
abnormal automaticity treatment
•decrease slope of phase 4 depolarization, and/or, •raise threshold of dischargeto less negative voltage (decrease frequency of discharge)
accessory tract pathway leading to arrythmias
Bundle of Kent
Class I anti arrhytmic
•Class I -fast channel blockers (Na+) •(IA) Quinidine, procainamide, disopyramide •(IB) Lidocaine, mexiletine •(IC) Flecainide, propafenone
Class II - anti arrythmic
b-blockers (Ca2+) • Propranolol, metoprolol, esmolol
Class III )
-inhibitors of repolarization(K+) •Amiodarone, sotalol, dofetilide
Class IV
calcium channel blockers (Ca2+) • Verapamil, diltiazem
overview class I ? dependance ?
•Block fast inward Na+ channels •Decreased Na+ entry slows rate of rise of Phase 0 depolarization •Cause in excitability and conduction velocity •Different properties depending on their affinity for Na+ channel •Possess use / state-dependence
Basically: Use/state dependence = cells discharging at abnormally high frequency are preferentially blocked
Class I act on what phases
- Slow rate of change of phase 0 •Slowing conduction, prolonging action potential & increasing ventricular effective refractory period
- Prolong phase 3 by an inhibiting K+ channels
- Intermediate speed of associationwith activated / inactivated Na+ channels & intermediate rate of dissociation
Effect of Class I on QT and QRS ?
Increase both
quindine overview and clinical uses
CLass 1A
•Concomitant Class III activity (block K+ channels) •Pro-arrhythmic •Due to toxicity is being replaced by Ca2+ antagonists
Clinical Applications •Suppression of supraventricular and ventricular arrhythmias
Replaced by more effective/safer antiarrhythmicagents
PK for Quinidine
Pharmacokinetics • Quinidine sulfate = rapid oralabsorption • Forms active metabolites (CYP 3A4) •Inhibits CYP 2D6, 3A4 & P-glycoprotein
Quinidine AE
•Arrhythmias (torsades de pointes) • SA & AV block or asystole • Nausea, vomiting & diarrhea (30-50%) •Thrombocytopenic purpura •Toxic doses – ventricular tachycardia (exacerbated by hyperkalemia) •Cinchonism(blurred vision, tinnitus, headache, psychosis) • Mixed a-adrenergic block & antimuscarinic properties • Can increase [digoxin] by decreasing renal clearance
Qunidine AE
•Do not use in patients with: • Complete heart block •Use with extreme caution in patients with: • Prolonged QT interval • History of Torsades de Pointes • Incomplete heart block • Uncompensated heart failure • Myocarditis • Severe myocardial damage
Procinamide MOA? clinical application ?
• Derivative of local anesthetic procaine • Similar actions to quinidine •Blockade of Na+ channels in activated state •Blockade of K+ channels •Antimuscarinic propertie
Clinical Applications •Suppression of supraventricular and ventricular arrhythmias Due to proarrhythmiceffects use should be reserved for life-threatening arrhythmias
Procinamide PK ?`
•IV • Metabolized by CYP 2D6 •Partly acetylated to N-acetylprocainamide (NAPA) which prolongs duration of action potential (class III)
Procinamide AE
Chronic use= high incidence of AE •Reversible lupus-like syndrome (25-30%) •Toxic doses: asystole, induction of ventricular arrhythmias • CNS effects (depression, hallucination, psychosis) • Weak anticholingeric effects • Hypotension
Prcinamide contraindications
Hypersensitivity • Complete heart block • 2nd degree AV block • Systemic lupus erythematosus (SLE) •Torsades de Pointes • Heart failure & hypertension (use with caution)
Dispyramide MOA ? clinical uses
•Strong negative inotropiceffect (> quinidine & procainamide) •Strong antimuscarinicproperties •Causes peripheral vasoconstriction • Blocks K+ channels
Clinical Applications • Suppression of supraventricular and ventricular arrhythmias
disopyramide AE
•Pronounced negative inotropiceffects •Severe antimuscariniceffects (dry-mouth, urinary retention, blurred vision, constipation) •May induce hypotension & cardiac failure without preexisting myocardial dysfunction
Class Ib anti arrythmics
Lidocaine / Mexiletine
Class Ib anti arrythmics overview ? what phases are effected
•Slow Phase 0 & decrease slope of Phase 4 • Shorten Phase 3 repolarization •Little effect on depolarization phase of action potential in normal cells •Rapidly associate and dissociate with Na+ channels
Class Ib effect on QRS and QT
QRS increases
QT decreases
lidocaine MOA ? PK ?
• Local anesthetic • More effect on ischemic or diseased tissue • Particularly useful in treating ventricular arrhythmias • LITTLE EFFECT on K+ channels
Pharmacokinetics •IV only (extensive first-pass metabolism)
clinical applications lidocaine
•Acute treatment of ventricular arrhythmias from myocardial infarction or cardiac manipulation (eg, cardiac surgery) •Treatment of digitalis-induced arrhythmias •Lidocaine’s use for VT has declined as a consequence of trials showing IV amiodarone to be superior • Little effect on atrial or AV junction arrhythmias
lidocaine AE
•Wide toxic-therapeutic ratio • CNS effects (drowsiness, slurred speech, agitation etc.) • Little impairment of left ventricular function •NOnegative inotropic effect •Cardiac arrhythmias (<10%) •Toxic doses: convulsions, coma
mixilitine MOA ?PK? AE
•Orally activederivative of lidocaine • Can be used both orally and IV
Clinical Applications Management of severe ventricular arrhythmias
Adverse Effects Mainly CNS & GI
