16. Cardiac Arrhythmia Drugs Flashcards
What causes arrhythmias?
Disturbance in pacemaker impuse formation, contraction impulse conduction, or a combination of the two.
What is the result of cardiac arrhythmias?
Timing and/or rate of contraction is insufficient to maintain normal cardiac output.
Describe the fast cardiac action potential in terms of ion movement and membrane potential.
Starts at -90mV, influx of Na+ causes depolarisation to +55mV, slight hyperpolarisation due to K+ efflux but stopped by Ca2+ influx, K+ efflux continues and Ca2+ influx stops causing hyperpolarisation back to resting -90mV.
What is the effect of drugs blocking Na+ channels on fast cardiac action potentials?
Slowing conduction in tissue, depolarisation happens more slowly and to lesser extent, action potential duration is slightly shortened.
What is the effect of beta-blockers on fast cardiac action potentials?
Phase 4 depolarisation is slowed so the duration of AP is prolonged.
What is the effect of drugs blocking K+ channels on fast cardiac action potentials?
The action potential duration is increased as slower hyperpolarisation so longer refractory period.
What is the effect of drugs blocking Ca2+ channels on fast cardiac action potentials?
Decreased inwards Ca2+ currents so decreased phase 4 spontaneous depolarisation.
Describe the slow cardiac action potential in terms of ion movement and membrane potential.
Funny channels allow Na+ and K+ influx causing slow depolarisation, Ca2+ influx causes quick depolarisation, K+ efflux then causes hyperpolarisation back to resting potential.
What is the effect of Ca2+ channel blockers on slow cardiac action potentials?
The slope of depolarisation is slower so conduction velocity reduced, the refractory period is later.
Which drugs affect automaticity of slow cardiac action potentials?
B agonists, muscarinic agonists, adenosine.
Which tissues of the heart have fast action potentials and which have slow?
Fast - cardiac tissue.
Slow - SAN or AVN.
What are the two broad mechanisms of arrhythmogenesis?
Abnormal impulse generation, abnormal conduction.
What are the causes of abnormal impulse generation in arrhythmias?
Automatic rhythms, triggered rhythms.
What are the automatic rhythms in arrhythmogenesis?
Enhanced normal automaticity from increased AP from SAN or ectopic focus from AP arising from other sites than SAN.
What are the triggered rhythms in arrhythmogenesis?
Delayed afterdepolarisation, early afterdepolarisation.
What are the causes of abnormal conduction in arrhythmias?
Conduction block and reentry.
What is conduction block?
Impulse is not conducted from the atria to the ventricles.
What are the two types of reentry loops?
Circus movement and reflection.
How does a reentry loop happen?
Pathway is blocked so impulse from one pathway travels backwards so cells are reexcited by the loop.
What are the four classes of action of drugs on arrhythmias?
Abnormal generation: decrease phase 4 slope or raise threshold. Abnormal conduction: decrease conduction velocity, increased effective refractory period.
What is the goal of pharmacology in arrhythmias?
Restore normal sinus rhythm and conduction to prevent more serious/lethal arrhythmias from occuring.
What are the general actions of antiarrhythmic drugs?
Decrease conduction velocty, change duration of ERP, suppress abnormal automaticity.
What is the action of a class Ia antiarrhythmic drug and give an example?
Moderate phase 0 - quinidine, procainamide.
What is the action of a class Ib antiarrhythmic drug and give an example?
No change in phase 0 - lidocaine.
What is the action of a class Ic antiarrhythmic drug and give an example?
Marked phase 0 - flecainide.
What is the action of a class II antiarrhythmic drug and give an example?
Beta-adrenergic blockers - propranolol, bisoprolol, esmolol.
What is the action of a class III antiarrhythmic drug and give an example?
Prolong repolarisation - amiodarone, sotalol, dofetalide, ibutilide.
What is the action of a class IV antiarrhythmic drug and give an example?
Calcium channel lockers - verapmil, diltiazem.
What are the effects of class Ia antiarrythmics on cardiac activity?
Decreased conduction, increased refractory period, decreased automaticity, increased threshold.
What are the effects of class Ia antiarrhythmics on ECGs?
Increased QRS, PR increased or decreased, increased QT.
What are the indications for use of quinidine?
Maintain sinus rhythm in atrial fibrillation and flutter, Brugada syndrome.
What are the indication for use of procainamide?
Acute IV treatment of supraventricular and ventricular arrhythmias.
What are the ADRs of class Ia antiarrhythmics?
Hypotension (from reduced CO), proarryhtmia, dizzy/confused/insomniac/seizures (high doses), GI effects, lupus-like syndrome (procainamide).
What are the effects of class Ib antiarrhythmics on cardiac activity?
Fast binding, no change in phase 0 of normal tissue, APD decreased, increased threshold, decreased phase 0 conduction in fast beating or ischaemic tissue.
What are the effects of class Ib antiarrhythmics on ECGs?
None in normal tissue but increased QRS in fast beating or ischaemic tissue.
What are the indications for class Ib antiarrhythmic use?
Acute in ventricular tachycardia.
What are the ADRs of class Ib antiarrhythmics?
Less proarrhythmic, CNS effects of dizziness/drowsiness, abdominal upset.
What are the effects of class Ic antiarrhythmics on cardiac activity?
Very slow binding, decreased phase 0 in normal tissue, decreased automaticity (increased threshold), increased APD and refractory period.
What are the effects of class Ic antiarrhythmics on ECGs?
Increased PR, QRS, and QT.
What are the indications of use of class Ic antiarrhythmics?
Wide spectrum, supraventricular arrhythmias, premature ventricular contractions, Wolff-Parkinson-White syndrome.
What are the ADRs of class Ic antiarrhythmics?
Proarrhythmia and sudden death with chronic use in structural heart disease, ventricular flutter, CNS and GI effects.
What are the cardiac effects of class II antiarrhythmics?
Increased AP duration and refractory period in AVN and slow AVN conduction, decreased phase 4 depolarisation.
What are the effects class II antiarrhythmics have on ECGs?
Increased PR, decreased HR.
What are the indications for use of class II antiarrhythmics?
Treat sinus and catecholamine dependent tachycardia, protect ventricles from high atrial rates, convent reentrant arrhythmias at AVN.
What are the ADRs of class II antiarrhythmics?
Bronchospasm, hypotension.
What are the cardiac effects of amiodarone?
Increased refractory period and AP duration, decreased phase 0 and conduction, increased threshold, decreased phase 4, decreased speed of AV conduction.
What are the effects amiodarone has on an ECG?
Increased PR, QRS, and QT; decreased HR.
What are the ADRs of amiodarone?
More serious with use past 3 months - pulmonary fibrosis, hepatic injury, increased LDL, thyroid disease, photosensitivity, optic neuritis.
What are the cardiac effects of sotalol?
Increased AP duration and refractory period, slow phase 4, slow AV conduction.
What are the ECG effects of sotalol?
Increased QT, decreased HR.
What are the indications of use for sotalol?
Supraventricular and ventricular tachycardia.
What are the ADRs of sotalol?
Proarrythmia, fatigue, insomnia.
What are the cardiac effects of class IV antiarrhythmics?
Slow AV conduction, increased refractory period in AVN, increased slope of phase 4 to slow HR.
What are the ECG effects of class IV antiarrhythmics?
Increased PR and HR can increase or decrease.
What are the indications of use for class IV antiarrhythmics?
Supraventricular tachycardia - control and convert.
What are the contraindications of class IV antiarrhythmics?
Partial AV block, B blockers (can get asystole), hypotension, decreased CO, sick sinus.
What are the ADRs of class IV antiarrhythmics?
GI problems.
What is the mechanism of action of adenosine?
Binds A1 receptors and activates K+ currents in AVN and SAN, decreases APD, hyperpolarises causing decreases HR. Decreased Ca2+ currents so increased refractory period in AVN.
What are the cardiac effects of adenosine?
Slows AV conduction.
What are the indications of use for adenosine?
Convert re-entrant supraventricular arrhythmias, hypotension during surgery, diagnosis of CAD.
What is the mechanism of action of vernakalant?
Blocks atrial specific K+ channels.
What are the cardiac effects of vernakalant?
Slows atrial conduction, increased potency with higher heart rates.
What are the ADRs of vernakalant?
Hypotension, AV block, sneezing and taste disturbance (these resolve).
What are the indications for use of vernakalant?
Convert recent onset AF to normal sinus rhythm.
What is the mechanism of action of ivabradine?
Blocks funny channel current in SAN.
What are the cardiac effects of ivabradine?
Slows sinus node but doesn’t affect BP.
What are the ADRs of ivabradine?
Flashing lights, teratogenicity not known.
What are the indications of use for ivabradine?
Reduce inappropriate sinus tachycardia, reduce heart rate in heart failure and angina.
What is the mechanism of action of digoxin?
Enhance vagal activity, slows AV conduction and slows HR.
What are the uses of digoxin?
Reduce ventricular rates in AF and flutter.
What is the mechanism of action of atropine?
Selective muscarinic antagonist.
What are the cardiac effects of atropine?
Block vagal activity to speed AV conduction and increase HR.
What are the uses of atropine?
Treat vagal bradycardia.
