Lecture 12 Flashcards
What are the objectives of anti-arrhythmic drugs?
Reduce morbidity Reduce mortality Ventricular arrhythmias lead to 70k deaths/year in the UK
What are the phases of a cardiac cation potential in ventricular myocytes?
Phase 0: rapid depolarisation, Na+ channels open, rapid influx into myocytes Phase 1: short depolarisation, K+ channels open, K+ efflux Phase 2: delay in repolarisation (Ca2+ entry via L-type channels) → small plateau Phase 3: rapid repolarisation, K+ channels open → K+ efflux → brings membrane potential back down Phase 4: automatically slow depolarisation → relatively flat as not peacemaker cells
What are the phases of a cardiac action potential in SA nodes?
Phase 4: slow depolarisation → causes pacemaker activity → mediated by if channels Phase 0: rapid influx of Ca via L type Ca channels Phase 3: repolarisation in channels → back to baseline
What is the refractory period?
Play crucial role in regulation of electrical impulses in heart, preventing arrhythmias Absolute refractory period → when there is an AP being fired, myocytes unresponsive to electrical stimulation → voltage-gated sodium channels inactivated Relative refractory period (vulnerable period) → followed ARP, could get an extra AP, could drive arrhythmias Supranormal period → excitable due to which channels are open - high chance of an extra beat
What are afterdepolarisations?
Extra depolarisations - not a full AP Early → during repolarisation Delayed → following complete repolarisation If they get big enough can cause arrhythmias Can occur if you don’t have enough K+ - cells → hyper excitable
What are the major modes of action to block arrhythmias?
Decrease phase 4 slope → slow rate Increase threshold potential → slow phase 0 Increase refractory period → lengthen AP Aim: to prevent re-entrant circuits (loops)
What is the Vaughan-Williams classification of anti-arrhythmic drugs?
Class I: sodium channel blockade Class II: catecholamine blockade Class III: lengthening of refractoriness Class IV: calcium channel blockade
What do sodium channel (class I) blockade anti-arrhythmic drugs do?
Restrict rapid inflow of Na+ during phase 0 Slows depolarization n conduction esp in damaged tissue Can also block K+ channels
Explain the 3 subtypes of sodium channel (class I) blockade anti-arrhythmic drugs
Sodium channel block w lengthened refractoriness EFFECT: makes AP longer → slows repolarization Blocks K+ channels EXAMPLE: quinidine, disopyramide n procainamide Sodium channel block with reduced refractoriness Doesn’t change rising phase Stop premature beats by holding channel inactivated → block voltage gated Na+ channels→ local anaesthetics like lidocaine, supresses premature beats Binds and unbinds quickly Sodium channel block with little effect on refractory period Slows rising phase, slows QRS Bind and unbinds slowly, general reduction in excitability, suppress re-rentrant rhythms EXAMPLE: flecainide
What do beta-andrenoceptor antagonist (class II) anti-arrhythmia drugs do?
Used for ventricular dysrhythmias following MI often [the drug increases sympathetic activation] EFFECTS Inhibits the effects of catecholamines like epinephrine and noradrenaline Reduce delayed afterdpolarisations due to symptoms activity Some ectopic pacemakers depend on adrenergic drive (useful for ectopic beats) Increases refractory period of AV node → prevent re-entrant tachycardia Useful if tachyarrhythmias are driven by overactive sympathetic system Membrane stabilising activity → less excitable
What do class III anti-arrhythmia drugs do?
Long elimination half life (10-100 days) thus given as loading dose Block K+ channels (Phase 3) → lengthen refractory period e.g. amiodarone - prolongs cardiac action potential → useful in re-entrant tachycardias, suppress ectopic activity ECG Prolongs QT, widens QRS Sotalol → non-selective beta-adrenoceptor blocker, prolongs cardiac AP → delays slow outward K+ current → not as effective as amiodarone but less adverse effects SIDE EFFECTS Photosensitive rash, thyroid abnormalities, pulmonary fibrosis
How can class III anti-arrhythmia drugs be pro-arrhythmic?
Can produce polymorphic ventricular tachycardia Dangerous when Taken w other drugs that lengthen the QT interval (e.g. antipsychotic drugs) Disturbed electrolyte balance (hypokalaemia) Hereditary prolonged QT Occurs if amiodarone taken w other specific drugs
What are class IV anti-arrhythmia drugs?
Ca2+ channel antagonists → block L-type Ca2+ channels in the heart Half-life 6-8 hours Considerable first pass metabolism Slow release preparation available EXAMPLE: verapamil Slow conduction in SA and AV nodes - as AP is carried by Ca2+ ions Slow the heart and terminate supra ventricular tachycardia (partial AV block) Shorten plateau of AP (phases 1 and 2) - less Ca2+ influx Reduce force of contraction Reduce after depolarisations Suppress ectopic beats ECG PR interval prolonged → slows conduction through AV node
What does adenosine do?
Receptors for adenosine in the heart at AV node → opens K+ channels → hyperpolarises AV node → slows conduction of beat → negative dromotropic effect Endogenous chemical mediator in the body (vasodilator) Acts via A1 receptors on AV node (hyper polarises cardiac tissue) Slows the rate of rise of pacemaker potential Slows conduction through AV node (negative dromotropic) Terminates paroxysmal supraventricular tachycardias Given as IV bolus (half life 8-10 seconds) - broken down very quickly
What do digoxin and other cardiac glycosides do?
Act directly in the heart → inhibit Na+/K+ ATPase pump → reduction in Na+ and Ca2+ exchange → less Na+ extrusion, reduces Ca2+ extrusion Increase in intracellular [Ca2+] increases excitability/contractility Decreases propagation and AP generation at SA and AV nodes Useful as slows conduction through AV node Enhances vagal activity by complex - indirect action bradycardia Useful in: atrial fibrillation, atrial flutter, heart failure
What are the characteristics of digoxin?
Eliminated 85% unchanged by the kidneys → renal failure digoxin accumulates Half life is 36horus - persists in body Given orally Low therapeutic index → small difference between therapeutic and toxic amount Treatment of overdose Use FAB fragment of antibody (Digibind), collates digoxin, No FC segment - no immune response
What is electroconversion?
Electric shock to reset rhythm of the heart → depolarises all heart muscle Direct current electric shock applied externally Successful shock: heart depolarised, ectopic focus extinguished, SA node resume dominant pacemaker Effects are immediate Supra/ventricular tachycardia, ventricular fibrillation, atrial fibrillation/flutter
What drugs are used to help atrial fibrillation?
Class II agents: β-blockers can help control ventricular rate via SA node Class IV agents: Ca2+ antagonists (e.g. Verapamil) slows conduction thru AV node
What is used to help atrial flutter?
Digoxin D.C. shock Class III agents: amiodarone/sotalol for maintenance Anticoagulants: if long standing condition to avoid emobli
What is used to help ventricular tachycardia?
Electrical conversion If patient is in good health IV lidocaine (class I agent) Failing that IV amiodarone Recurrent episodes Amiodarone or sotalol
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What is the Maze procedure?
Treatment of atrial fibrillation when drugs do not control the condition Create incisions in the atrium → disrupt re-entrant circuits Once incisions are made → sew together again Atrium can hold blood but electrical impulse can’t cross incisions RESULT: one path that electrical impulse takes from SA to AV node Atrium can no longer fibrillate n sinus rhythm is restored
What is catheter ablation?
Apply radiofrequency (RF) /electrical energy or freezing offending area (usually via catheter) Creates small scar that is electrically inactive → incapable of generating heart arrhythmias
