ANTI-ARRHYTHMICS AND WARFARIN. Dr Nithish Jayakumar
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1 ANTI-ARRHYTHMICS AND WARFARIN Dr Nithish Jayakumar
2 Contents 1. Anti-arrhythmics Pacemaker and myocardial potentials Drug classes mechanisms; s/e; contra-indications Management of common arrhythmias 2. Warfarin Coagulation cascade Warfarin in VTE mechanisms; s/e; contra-indications; monitoring Warfarin reversal
3 Pacemaker & myocardial potentials Pacemaker potentials Originate at rapidly conducting tissue SAN AVN Bundle of His Ventricular fibres SAN ordinarily sets the pace [70-80/min] Sympathetic and parasympathetic input Myocardial potentials Stimulated by pacemaker potentials Atrial and ventricular muscle Sympathetic input only
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5
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7 Fast Na closes K channels open Plateau due to Ca inflow prolongs action potential Cardiac cell stimulated fast Na channels open Ca channels close increased K outflow for rapid repolarisation Cell membrane returns to resting potential
8 Anti-arrhythmics Vaughan-Williams classification According to predominant mechanism of action 4 classes Amiodarone; digoxin; adenosine Rx for tachyarrhythmias [Atropine]
9 Tachyarrhythmias Enhanced automaticity More active than usual (catecholamines; sepsis; electrolyte imbalance) Triggered activity Re-entry A propagating impulse fails to die out after normal activation of the heart and persists to re-excite the heart after expiration of the refractory period
10
![Class Site Mechanism Example I [Ia; Ib; Ic] Block Na channels Reduces action potential duration Ic: flecainide [Amiodarone] II Block beta-1 receptors Negative inotropy/chronotropy Bisoprolol](/docs-images/85/92398218/images/11-3.jpg "Metoprolol [Amiodarone] III Block K channels (specifically nodal) Increases refractory period Amiodarone Dronedarone Sotalol IV Block Ca channels Negative inotropy/chronotropy Verapamil Diltiazem")
11 Class Site Mechanism Example I [Ia; Ib; Ic] Block Na channels Reduces action potential duration Ic: flecainide [Amiodarone] II Block beta-1 receptors Negative inotropy/chronotropy Bisoprolol Metoprolol [Amiodarone] III Block K channels (specifically nodal) Increases refractory period Amiodarone Dronedarone Sotalol IV Block Ca channels Negative inotropy/chronotropy Verapamil Diltiazem [Amiodarone]
12 Atrial tachycardia Atrial flutter Narrow complex Atrial fibrillation AVRT Supraventricular AVNRT Tachyarrythmias Broad complex SVT with aberrant conduction Ventricular Ventricular tachycardia Ventricular fibrillation
13 Atrial fibrillation Multiple re-entry mechanisms Class I (Na) Class II (Beta-1) Class III (K) Class IV (Ca)
14 Rate vs rhythm control Atrial fibrillation Indication in AF Mechanism Contraindications Side-effects Flecainide Paroxysmal AF ( pill in the pocket ) Class Ic Structural heart disease LVF Proarrhythmic AV blocks Dizziness
15 Rate vs rhythm control Atrial fibrillation Indication in AF Mechanism Contraindications Side-effects Amiodarone Maintain sinus rhythm Class III [all classes] AV block Pneumonitis Bradycardia/AV block Hepatitis Photosensitivity Hypo/hyperthyroidism Prolongs QT
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17 Heart failure and AF Atrial fibrillation Avoid class IV (negatively chronotropic) Rate control with beta-blocker ideal Digoxin is alternative when other rx failed Digoxin Indication in AF Rate control in heart failure Mechanism Side-effects Monitoring Increases vagal tone (less so in exercise) Na/K-ATPase inhibitor positively inotropic GI s/e anorexia; N&V; diarrhoea AV block Dizziness Heart rate Renal function renal clearance Hypokalaemia
18 Digoxin effect therapeutic doses Reverse-tick ST depression
19 Digitalis toxicity Clinical features Cardiac any arrhythmia; PVC / brady GI symptoms anorexia; N&V; diarrhoea CNS symptoms Visual changes [yellow-green distortion] Drowsiness Lethargy Headache Biochemical features Hyperkalaemia [renal dysfunction] Serum digoxin level Management Digifab (digoxin-specific antibody fragments)
20 Re-entry mechanism AVN is focus of re-entry AVNRT Class I (Na) Class II (Beta-1) Class III (K) Class IV (Ca)
21 AVNRT Vagal maneuvers adenosine BB/CaCB/dig Indication in AVNRT Mechanism Contraindications Side-effects Adenosine Termination - A1 receptors at SAN opens K channels - Ca blocker at AVN AF in WPW Severe asthma Severe coronary artery disease Flushing Chest pain Bronchospasm AV block
22 AF in WPW Accessory pathway with antegrade conduction Class I (Na) Class III (K) Class II (Beta-1) Class IV (Ca) X X Adenosine X
23
24 VT Usually secondary to structural heart disease Class I (Na) Class II (Beta-1) Class III (K) Class IV (Ca)
25 Electrical cardioversion VT Amiodarone Indicated in haemodynamically unstable/pulseless (as per ALS) and haemodynamically stable VT Lidocaine Class Ib
26 Atropine Atropine Indication Mechanism Contraindications Side-effects Symptomatic bradyarrhythmias Muscarinic receptor antagonist - Inhibits vagal activation at nodes Glaucoma Ileus BPH Anticholinergic effects: - Dilated pupils - Blurred vision - Dry mouth - Tachycardia - Constipation - Urinary retention
27 Warfarin INR
28 Warfarin INR is the standardised measure of prothrombin time PT measures extrinsic and common pathways [VII; X; V; II; fibrinogen]
29 Warfarin Indication Mechanism Contra-indications Cautions Side-effects Monitoring Anticoagulation DVT/PE & AF Inhibits the conversion of vitamin K to its active form - Active vitamin K carboxylates 2, 7, 9, 10 [protein C & S] - Without carboxylation, cannot bind Ca and form effective coagulation complex Haemorrhagic stroke Significant bleeding Pregnancy Liver failure - Increased risk of bleeding [recent surgery; recent ischaemic stroke; recent GI bleed; peptic ulcer; severe hypertension] - Drug interactions [enzyme inducers & inhibitors] - Other interactions [cranberry juice; ETOH] Bleeding Skin necrosis Hepatic dysfunction GI s/e N&V; diarrhoea INR
30 Warfarin in AF
31 Warfarin and bleeding risk
32 Warfarin in DVT/PE Initiated with heparins Heparins continued for minimum 5 days post DVT/PE Once-daily regimen Load with 10/5/5 usually (lower in elderly; liver/renal/heart failure) 10mg od 5mg od 5mg od Check INR each day After initiation protein C and VII levels fall first may be initially procoagulant (warfarin skin necrosis protein C deficiency) Heparins stopped when INR in therapeutic range for 2 consecutive days
33
34 INR targets AF 2.5 DVT/PE 2.5 Recurrent DVT/PE 3.5 Metallic valve Warfarin Duration of warfarin therapy First DVT/PE, reversible cause = 3 months Idiopathic first DVT/PE = 3 months or long-term Recurrent DVT/PE = indefinite DVT/PE and cancer = LMWH for 3-6 months then long-term Anticoagulation clinic referral for regular follow-up Yellow book for INR monitoring
35 Warfarin reversal Major bleeding associated with warfarin: Intracranial haemorrhage GI bleed Urgent surgery 1. Stop warfarin 2. Vitamin K IV 5mg over 20-60mins (12 hrly) 3. Prothrombin complex concentrate [2, 7, 9, 10, protein C & S] Alternative is fresh frozen plasma PCC corrects the defective coagulopathy without risks of transfusion reactions
36 Warfarin reversal INR >8; minor bleeding 1. Stop warfarin 2. Vitamin K IV 1-3mg 3. Restart warfarin when INR <5.0 INR >8; no bleeding 1. Stop warfarin 2. Vitamin K 1-5mg oral 3. Restart warfarin when INR <5.0 INR 5 8; minor bleeding 1. Stop warfarin 2. Vitamin K IV 1-3mg 3. Restart warfarin when INR <5.0 INR 5 8; no bleeding 1. Hold 1 or 2 doses of warfarin 2. Recheck INR and reduce subsequent maintenance dose
37 Warfarin reversal Peri-operative 1. Stop warfarin 5 days in advance 2. If high risk bridge with LMWH
38 Thanks for listening! Good luck! Any questions?
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