Lecture 8.1 - Arrhythmics.pdf

Heart block: ◦Heart block can lead to low HR when severe -> low CO -> low BP (patient can become hemodynamically unstable) ◦Atropine: ‣ Decrease parasympathetic activity ‣ Block binding of acetylcholine from binding to receptors in AV node ◦Epinephrine:...

Heart block: ◦Heart block can lead to low HR when severe -> low CO -> low BP (patient can become hemodynamically unstable) ◦Atropine: ‣ Decrease parasympathetic activity ‣ Block binding of acetylcholine from binding to receptors in AV node ◦Epinephrine: ‣ Increase sympathetic activity ◦Pacing - transcutaneous, transvenous, permanent Antiarrhythmics: ◦Vaughan William classification ‣ Based on their ability of abolishing arrhythmia by blocking specific ion currents during the action potential Class I (sodium channel blockers) Class II (beta blockers) Class III (potassium channel blockers) Class IV (calcium channel blockers) Class I (sodium channel blockers): ◦Block fast, voltage-gated sodium channels responsible for phase 0 in contractile cells only ◦Sub-classified into Class 1a, 1b and 1c, based on how they block the channel ‣ 1c > 1a > 1b - in terms of strength of blocking channel ◦Class 1a and 1c drugs block sodium channels in both activated and inactivated states ◦Class 1b drugs block sodium channels in inactivated state Class I (sodium channel blockers): ◦Sodium channel blockade: 1c> 1a> 1b ◦Effects on action potential duration (APD) and effective refractory period (ERP): ‣ Class 1a - prolong the APD, ERP ‣ Class 1b - shorten the APD, ERP ‣ Class 1c - no change ◦Effects on ECG: ‣ Class 1a - prolong both the QRS and QT ‣ Class 1b - no effect on the QRS, slightly shorten the QT ‣ Class 1c - markedly prolong the QRS, minimal effect on the QT ◦Class 1A - e.g. Quinidine ◦Class 1B - e.g. Lidocaine ◦Class 1C - e.g. Flecainide Class II (beta blockers): ◦Block binding of epinephrine/norepinephrine to beta-adrenergic receptors in nodal and contractile cells ◦Slows phase 4 depolarisation ◦Slow the sinus rate (HR), prolong AV nodal conduction (reduces) ◦Prolong APD and ERP  ◦Example - Metoprolol, esmolol Class III (potassium channel blockers): ◦Block potassium currents that repolarise the heart during phase 3 of the action potential - affects contractile cells ◦Prolong APD, ERP - phase 3 is delayed ◦E.g. Amiodarone, Ibutilide Class IV (calcium channel blockers): ◦Calcium channel blockers (block L-type calcium channels) ◦Slow phase 4 depolarisation in nodal cells ◦Decrease AV noal conduction velocity ◦Prolong APD, ERP ◦E.g. Verapamil Class V (adenosine): ◦Adenosine binds to alpha-1 adenosine receptors in nodal cells ◦Activate G inhibitory proteins -> gamma subunit -> increase potassium efflux -> cause hyperpolarisation of cells -> takes longer to reach threshold potential ◦Activate G inhibitory proteins -> alpha and beta subunit -> inhibit adenylate cyclase -> block calcium channels ◦Slows AV nodal conduction velocity, increase AV node refractory period ◦Very short half-life, so only administered as IV Class V (Digoxin): ◦Most common cardiac glycoside derived from foxglove plants ◦Digoxin stimulate increase acetylcholine release from vagus nerve (ACH binds to muscarinic receptors) ◦Activate G inhibitory proteins -> gamma subunit -> increase potassium efflux -> cause hyperpolarisation of cells -> takes longer to reach threshold potential ◦Activate G inhibitory proteins -> alpha and beta subunit -> inhibit adenylate cyclase -> block calcium channels ◦Slows AV node conduction velocity, increase AV node refractory period ◦Digoxin also increases contractility of the heart (hence used in heart failure) Arrhythmias - rate control or rhythm control?: ◦Non-pharmacological methods (carotid sinus massage, Valsalva manoeuvre) may terminate the SVTs in stable patients ◦Rate control: ‣ SVT (increased automaticity/re-entry circuits/triggered activity) all passing via AV node to ventricles Atrial tachycardia, ACNRT, FAT, MAT ‣ Supraventricular arrhythmias (all passing via AV node) Atrial fibrillation, atrial flutter ‣ Rate control reduce conduction via AV node ‣ Adenosine, beta blockers (class II), calcium channel blockers (class IV), digoxin (ABCD) ◦Rhythm control: ‣ Re-entry circuits/triggered activity in atria or in ventricles ‣ Increased excess automaticity to ventricles via other accessory pathways and not AV node  Atrial fibrillation, atrial flutter, VT, Torsades de pointes ‣ Rhythm control reduces these additional currents and restore sinus rhythm ‣ Sodium channel blockers (class I), Potassium channel blockers (class III), beta blockers ◦SVT (sinus tachycardia, AVNRT, FAT, MAT): ‣ Rate control acutely with adenosine - adenosine is short acting ‣ Prophylactic with beta blockers or calcium channel blockers ◦Atrial fibrillation/flutter: ‣ Rate control with beta blockers, calcium channel blockers, digoxin ‣ Rhythm control with sodium channel blockers, potassium channel blockers ‣ Risk of stroke is high with atrial fibrillation -> need to consider anticoagulants ◦VT: ‣ Rhythm control with sodium channel blockers, potassium channel blockers (classes I and III) ‣ Beta blockers to reduce the sympathetic activity ◦Torsades de pointes - polymorphic ventricular tachycardia: ‣ Magnesium to reduce QT interval - could help establish the Na+/K+ pump for cells ‣ Class 1b If hemodynamically unstable: ◦If hemodynamically unstable (low BP, chest pain, syncope, severe heart failure): ‣ Cardioversion (electrical or chemical cardioversion) - synchronise pulses with QRS complex (mainly R wave) ◦Defibrillation - asynchronised pulse given ◦Long term treatment - radiofrequency ablation of the affected tissue e.g. WPW Adverse drug reactions: ◦Beta blockers: ‣ Suppress AV node -> bradycardia ‣ Reduced contractility -> reduce CO -> hypotension (especially in patients with heart failure) ‣ These also block beta 2 receptors in bronchioles -> bronchospasm -> COPD, asthma ‣ Glucagon can be given as an antidote ◦Calcium channel blockers: ‣ Suppress AV node -> bradycardia ‣ Reduced contractility -> reduce CO -> hypotension (especially in patients with heart failure) ‣ Could decrease GI motility -> constipation ‣ Calcium can be given as an antidote ◦Adenosine: ‣ Sense of impending doom ‣ Bronchospasms (short-lived) ‣ Chest pain ‣ Increased blood flow to skin capillaries -> flushing ‣ Arteriole vasodilation -> hypotension (not profound since adenosine has a short half-life) ◦Digoxin: ‣ Cholinergic side effects (nausea, vomiting, diarrhoea) ‣ Inhibits sodium-potassium ATPase - hyperkalaemia ‣ Increase calcium within cells -> DADs -> VT  ‣ Hypokalaemia can increase digoxin toxicity (K+ competes with digoxin for receptor binding) ‣ Digibind can be given as an antidote ◦Sodium channel blockers: ‣ Class 1a: have weak potassium channel block -> prolong ERP/APD -> prolong QT interval -> increased risk of EAD -> Torsades de pointes ‣ Class 1b: CNS stimulation or depression ‣ Class 1c: pro-arrhythmic in patients with ischaemic or structural heart disease ◦Potassium channel blockers: ‣ Prolong QT interval -> increased risk of EAD -> Torsades de pointes