Anti-Arrhythmic Drugs Flashcards
Drugs which Induce Dysrhymias
Sympathomimetic Drugs: Increase automaticity
Digitalis • Drugs prolonging QT time: – Anti-dysrhythmic drugs – Antihistamines – Antipsychotics – Cisapride, etc.( Torsades de pointes)
Anti-Dysrhythmic drugs
Anti-dysrhythmic effects via – cardiac automaticity – in SA or AV node • All have an effect on ion flux across membranes. – prolong AP – effective refractory period
Vaughan-Williams Classification of antidysrhythmic drugs
CLASS I : Na channel blockers
CLASS II : Beta blockers
CLASS III: K channel blockers
CLASS IV: Ca channel blockers
Other drugs digoxin, adenosine, etc.
Class 1 Anti-dysrhythmic drugs
All block rapid sodium channels, therefore prolong the refractory period in myocardial tissue where the AP is dependent on sodium flux, like atrial myocytes, His-Purkinje system and ventricular myocardium. • So: effective for re-entry dysrhythmia
What do different classes of drugs do?
CLASS IA: Open channels
CLASS IB: Inactive channels
CLASS IC: Open channels
Class 1A
Quinidine
Procainamide
Disopyramide
Open channels Dissociates slowly Inhibits fast sodium channels (intermediate effect) Prolong APD by blocking potassium efflux channels. Prolongs repolarization Delay conduction via atria, AV node, bundle of His Prolong ventricular refractory and QT interval
Quinidine
Class 1A Isomere of Quinine – cinchona bark • Use declined due to side effects • Indications: – Supraventricular and ventricular dysrhythmias
Quinidine: Side effects
• 30% - GIT: nausea, vomiting, diarrhoea • Hypotension: Especially with IV: ? Alpha antagonist • Cinchonism: headache, tinnitus, visual disturbances • Hypersensitivity: thrombocytopenia • Widening of QRS and QT prolongation – Torsades de pointes – “Quinidine syncope" : – Sudden death (0.5 – 4%)
Procainamide
Effect like quinidine • SE: – Lupus: reversible arthralgia and rash • Indications: – Less hypotension – Oral/IV: supraventricular and ventricular dysrhythmias – Use generally less than before
Disopyramide
1A
Oral for ventricular dysrhythmias
• Negative inotropic and antimuscarinic.
– Caution in heart failure and elderly
Class 1B
Inhibit fast sodium channels WEAKEST SODIUM CHANNEL BLOCKERS: little change in QRS duration in normal cardiac tissue and minimal effect on repolarization. Shorten repolarization Shorten duration of AP and refractory period – Lidocaine = lignocaine
Lidocaine
Only IV; Extensive first pass metabolism
• Therapeutic range: 2-6 ug/ml
• Metabolism dependent on liver blood flow:
Congestive heart failure, cardiogenic shock
leads to raised plasma levels
• Propranolol, verapamil, cimetidine may cause
increased levels
• Indication: Ventricular tachy-dysrhythmias
SE of Lidocaine
CNS: ( > 5 ug/ml) – Circum-oral paresthesia – Tinnitus – Slurred speech – Confusion – Drowsiness – Convulsions, CNS suppression • Delay conduction in in normal cardiac tissue
Mexiletine
Class 1B
Oral for sympotomatic ventricular dysrhytmias
Class 1C
Flecainide, Propafenone • More potent effect op fast sodium channels • Suppress Phase 0 of AP • Delay depolarisation significantly • Delay conduction • Minimal effect on repolarisation
Flecainide
Indications:
Supraventricular dysrhythmias and lifethreatening ventricular dysrhythmias
• SE:
SE of Flecainide
– Increase mortality in patients after myocardial infarction – Bronchospasm – Leukopenia, Thrombocytopenia – Convulsions
Class II: B-blockers
Types
MOA
No-selective: Propranolol, Sotalol and Timolol
Cardio-selective: Atenolol,Metoprolol and Esmolol
A and B-Blockers: Labetalol and Carvedilol
Class II
Inhibit sympathetic activity: therefore • cardiac automaticity and conduction – ↓ heart rate – ↓ AV conduction
Prevent shortening of refractory period on all levels. ischemia-dependent VF, exercise induced dysrhythmias, prolonged QT syndrome
SE of B-blockers
Bronchospasm • Heart failure • Bradycardia; AV Block • Peripheral arterial insufficiency in patients with peripheral vascular disease or Raynaud’s • Depression • Dreams • Sexual Dysfunction
Class III: K+ Channel Blockers
Suppress re-entry dysrhythmias, except TdP, in atria and ventricles. Especially effective in AF, atrial flutter, and monomorphic ventricular tachycardia. More pronounced prolongation of AP @ slow heart rate: “reversed use-dependent.
Class III: K+ Blockers,Drugs
Amiodarone
• Ibutilide
• Dofetilide
• Sotalol
Amiodarone
K channel blocker • Na channel blocker: (Class 1a) • Alfa & Beta – blocking activity (non-competitive; weak) • Calcium channel blocker • Oral/ IV • T½: 30-60 DAYS • Indications: Supraventricular and Ventricular dysrhythmias
Amiodarone: SE
Causes dysrhythmias in 2%, but seldom Torsades de pointes – Hypotension, AV block, various other dysrhythmias • Severe pulmonary fibrosis – Fatal • Blue discolouration of face (5%) • Thyroid dysfunction (5%) • Yellow/brown discolouration of eyes • Hepatic dysfunction: may be irreversible • Constipation (20%)
Amiodarone-Drug Interactions
Inhibits CYP3A and P-glycoprotein.
• Digoxin, warfarin, anti-dysrhythmic
drugs, anticonvulsants, etc.
Class IV: Calcium Channel Blockers
Non-dihydropyridine calcium channel blockers: Block L- type, high voltage- calcium channels Verapamil and Diltiazem : – SA & AV node – Decrease SA Automaticity – Decrease AV Node conduction velocity – Slow down ventricular rate during AF
Indications for Class IV drugs
For acute supra-ventricular tachydysrhythmias
• Heart rate control in AF.
– Lower both resting and exercise heart rate
(digoxin lowers heart rate during rest in AF).
• Also prevent VT or VF due to coronary
artery spasm.
Other anti-dysrhythmic drugs
Digitalis: Atrial fibrillation and severe heart
failure
• Adenosine: Supraventricular tachycardia
• Magnesium: Ventricular and
supraventricular dysrhythmias
• Adrenaline: Cardiac arrest and fibrillation
• Atropine: bradycardia
Adenosine
Drug of choice for acute PSVT • t½ = 10 seconds. • Mechanism of action: • Activates adenosine (A1) receptors – →Activates Ach-sensitive K channels and blocks Ca influx – →Suppresses SA and AV nodes, vasodilation of coronary vessels • Cell hyperpolarizes
Adenosine and Pharmcological Cardioversion
AV node conduction is blocked completely for a
couple of seconds short asystole
Terminates SVT by preventing retrograde
conduction of re-entry impulses via AV node.
Side effects of Adenosine
Blushing (20%) • Shortness of breath, bronchospasm • Headache • Hypotension • Nausea • Paresthesia • CONTRA INDICATION : HEART TRANSPLANT
Digoxin
vagal tone, slows AV conduction and prolongs AV node refractory period. • Used in AF for rate control (β-blockers and CCBs preferred: more rapid onset of action and AV node blockade) • Digoxin: – < bradycardia than β-blockers, – < cardiac contractility than verapamil.
Magnesium Sulfate
Mg due to loop diuretics or pathology: dysrhythmias, CHF. i.v. INDICATIONS: • HYPOMAGNESEMIA • DIGOXIN TOXICITY • TORSADES DE POINTES
