Cardiac Arrhythmias Lecture Notes PDF

Cardiac Arrythmias By Rida Jamil Sinoatrial Node Pacemaker Potential - Pacemaker cell membranes contain HCN- gated channels (Hyperpolarisation- activated cyclic nucleotide-dependent non-specifi c channel) - If is activated by hyperpolarisation, then causes slow depolarisation to...

Cardiac Arrythmias By Rida Jamil Sinoatrial Node Pacemaker Potential - Pacemaker cell membranes contain HCN- gated channels (Hyperpolarisation- activated cyclic nucleotide-dependent non-specifi c channel) - If is activated by hyperpolarisation, then causes slow depolarisation toward AP threshold - Threshold for AP formation - Phase 4: Prepotential permits automaticity  activated by hyperpolarisation (phase 3), HCN creates a ‘funny current’  simultaneously effl ux's K+ and infl ux's Na+. Reaches threshold and upstroke inactivates HCN  Sinoatrial Node Pacemaker Potential - Phase 0: upstroke of the slow pacemaker action potential, it is triggered at threshold potential (-55 mV) and increases the movement of Ca2+ into the cell - Phase 3: Ca2+ channels are inactivated and delayed K+ efflux. Increased K+ efflux so membrane hyperpolarises - Phase 4: Pacemaker Na+ influx (If), Ca2+ channels recover from inactivation and pumps restore ion gradients - The rate of firing of the SA node sets the heart rate and initiates the cardiac cycle Sympathetic nerves and - Activation causes release of NA  binds to B1 heart rate adrenoreceptors on the cardiac pacemaker and myocyte cell membranes - Increases opening of HCN channels in pacemaker cells  increase Na+ infl ux - Opens Ca2+ channels and increased Ca2+ infl ux - Increases slope of prepotential (phase 4) - Heart rate increases Para-sympathetic nerves and heart rate - Activation causes release of acetylcholine – binds to muscarinic cholinergic receptors - Decreases opening of HCN channels  decreased Na infl ux - Slows opening of Ca2+ channels  decreased Ca2+ infl ux - Opens additional K+ channels (ligand gated)  increased K+ effl ux - Hyperpolarises membrane and reduces slope of prepotential and heart rate decreases Ventricular myocyte action - P h a s e 0 = Ra p i d d e p o l a r i z a t i o n o c c u r s potentials w h e n t h e m e m b r a n e p o t e n t i a l re a c h e s a c r i t i c a l fi r i n g t h re s h o l d ( - 6 0 m V )  i n w a rd c u rre n t o f N a + - P h a s e 1 = Pa r t i a l re p o l a r i z a t i o n o c c u r s a s t h e N a + c u rre n t i s i n a c t i v a t e d ; f a s t K+ channels open - Phase 2 =Ca2+ channels open and fast K+ channels close - Phase 3 = Ca2+ channels inactivated, allowing slow K+ channels being activated. - P h a s e 4 = Re s t i n g p o t e n t i a l Vagal tone - Intrinsic rate of fi ring of S AN cells ~ 100 -110 APs per min - Constant tonic activation of some parasympathetic nerves on S A node Early after depolarisations (EADs) - Occurs when heart rate is low and supressed by high HR - Occurs when AP is prolonged and some Ca channels inactivated during shoulder - Reactivate to give EAD - Ca L channels – end phase 2 - Ca T channels – mid phase 3 - Need diff erent drugs to Rx Delayed After Depolarizations (DADs) - Seen at increased HRs - Associated with elevated Ca2+ - Ca2+ activation of Na/K channels (depolarising) - Na/Ca exchange 3:1 = electrogenic - Toxic doses of cardiac glycosides What drugs are used to treat bradycardias - Atropine  switches to vagus nerve - Isoproterenol (isoprenaline)  activates beta receptors - Pacing Atropine - N a t u r a l l y o c c u rr i n g a n t i m u s c a r i n i c a l ka l o i d ( c o m e s f ro m b e l l a d o n n a = d e a d l y nightshade) - B l o c k s v a g a l i n h i b i t i o n o f S i n u s a n d AV node - Given by IV - Pre d o m i n a n t l y m e t a b o l i s m b y t h e l i v e r - S h o r t h a l f- l i f e = ~ 3 h r s - A n t i c h o l i n e rg i c e ff e c t s : d r y m o u t h , mydriasis and postural hypotension Adenosine - Use to treat tachycardias, mainly re-entry supraventricular tachycardia (e.g. Wolff -Parkinson-White syndrome – when there is a hole in your fi brous tissue and the electrical current activates the AV node and stimulates the S A node, giving heart no time to rest) - Hyperpolarises cardiac conducting tissue and slows the rate of the rise of pacemaker potential, works on AV node - Administered IV, to terminate paroxysmal SVTs, action lasts only 20-30 secs, SVT terminated patient remains in sinus rhythm. - Side-eff ects: chest pain, shortness of breath, dizziness and nausea Drug treatment for cardiac arrest - Asystole = when there is no stimulation and heart is not working, give adrenaline - Ventricular fi brillation = when there is electrical activity, but ventricles don’t contract together, give Amiodarone & Lignocaine What is used to treat tachycardias - Class 1  Na channel blockers (blocks phase 0) - Class 2  Beta blockers (something with S A node) - Class 3  K channel blockers (block phase 3) - Class 4  Ca channel blockers (blocks phase 2) Class 1 antiarrhythmic drugs - Divided into 3 groups and according to their eff ect on the action potential duration - Class 1a: Lengthen action potential duration and refractory period (e.g. Quinidine, Procainamide & Disopyramide) - Class 1b: Shortens action potential duration and refractory period (e.g. Lignocaine/Lidocaine) - Class 1c: No eff ect on action potential duration and refractory period. Delays conduction velocity in Purkinje fi bres (e.g. Flecainide) Lidocaine - It blocks fast sodium channels and slows phase 0 depolarisation, shortens action potential duration & specifi c eff ect on rapidly depolarising tissue (use dependent eff ect) - Indications is ventricular arrhythmias - Indication  Approved or recommended use of medication to treat a specifi c disease or condition - Pharmacology: Short half-life, must be given as bolus plus IV fusion, not absorbed via oral route (hepatic fi rst pass metabolism), hepatic clearance decreased in elderly, heart failure and liver disease - Adverse eff ects: Hypotension, Heart block, Neurotoxicity and fi ts (seizures) Class 2 drugs - B e ta bl oc ke rs - N on- c a rdi o se l e c t i v e – a l s o bl oc ks B 2 re c e pt ors ( Propra nol ol ) - Ca rdi o s e l e c ti v e – Le ss pot e nt bl oc ke rs of B 2 re c e ptors ( At e nol ol ) - Othe rs ( B re ty l l i um ) - The y a re be ta a dre nore c e pt or a nt a goni s ts, re duc e s i nt ri nsi c ra te i n si nus a nd AV node s, re duc e s H R , bl ood pre ss ure , c a rdi a c work a nd re ni n se c re ti on. - B 1 se l e c t i v e ( At e nol ol , M e toprol ol ) & B 1 a nd B 2 se l e c t i v e ( Propra nol ol )  gi v e n ora l l y a nd I V ( m e toprol ol a nd propra nol ol ) use , fi rs t pa ss he pa ti c m e t a bol i sm ( e. g. propra nol ol ) a nd re na l exc re t i on ( e. g. a te nol ol ) Adverse eff ects of Class 2 drugs - B1 eff ects: Bradycardias and Heart failure - B2 eff ects: Exacerbation of asthma, cool peripheries, muscular aches, worsening intermittent claudication - Other severe eff ects are fatigue, nightmares, sleep disturbances, withdrawal eff ects (angina and MI) and unawareness of hypoglycaemia  this is when Beta blockers cross the BBB Class 3 drugs - Amiodarone prolongs the AP duration and refractory period, lengthening QT interval on ECG - Indications are eff ective for ventricular & supraventricular tachycardia, fi rst-line treatment of ventricular fi brillation & improves survival in patients with recurrent ventricular tachycardia - Pharmacology: Long half-life and Hepatic metabolism - Adverse eff ects: Serious adverse eff ects limit use to high-risk patients: Thyroid disturbances, Pulmonary fi brosis, Pro -arrythmia and torsade de pointes, Peripheral neuropathy, Hepatitis and Blue- grey skin discolouration Class 4 drugs - Dihydropyridines: Nifedipine and Amlodipine  predominantly vascular eff ects (arterial vasodilation) - Benzothiazepines: Diltiazem  Mixed vascular and cardiac eff ects - Phenylalkylamine: Verapamil  Predominantly cardiac eff ects (-ve inotrope and chronotrope, antiarrhythmic) Verapamil - It is a Ca2+ channel blocker, slows phase ½ slow Ca2+ entry and reduces rate and contraction velocity in sinus and AV node - Indications: Supraventricular arrythmias - Pharmacology: Actions on the heart >> actions on the blood vessels (c.f. nifedipine), oral and IV use, fi rst pass hepatic metabolism - Adverse eff ects: Heart failure, hypotension, constipation, vasodilation, oedema and fl ushing - It can cause heart failure by stroke volume reduced and HR