Anti-Arrythmic Agents Flashcards
Incidence of Cardiac Arrythmias
5% of population
25% of patients under general anesthesia
80% of patients with acute myocardial infarction
All Arrhythmias result from
1) Disturbed impulse formation
2) Disturbed impulse conduction
3) Combination of 1 and 2
EAD
Early after depolarization
Usually at slow heart rates
Depolarizes on repolarization plateau (before it gets all the way down)
DAD
Delayed afterdepolarization
usually at fast heart rates
From resting potential
Re-entry
1) Block
2) Unidirectional conduction
3) Slow conduction through the block
Anti-arrhythmic therapy
Reduce ectopic pacemaker activity an/or modify conduction characteristic to disable re-entry circuit
Possible pharmacological mechanisms
1) Na channel blockade
2) Blockade of sympathetic autonomic effects (B-receptors)
3) Prolongation of the effective refractory period
4) Ca channel blockade
Ways to reduce rate of abnormal pacemaker activity
1) Reduction of phase 4 slope (B=blockers)
2) Increase of max. Em (hyperpolarize membrane with adenosine)
3) Increase of threshold potential (Na or Ca channel blockers)
4) Increase of AP duration (K channel inhibitors)
Use-dependent/state-dependent drug action
Selective blockade of depolarized cells
Channels that are used frequently/inactivated are more susceptible (ie during tachycardia or in ischemic/infarcted tissues)
Whereas channels in normal cells loose drug during resting phase
(anti-arrhythmics are no specific though, so can induce arrhythmias in normal cells)
Should you treat aymptomatic or minimally symptomatic arrhythmias?
NO
Class I
Na channel blockers
Class II
B-adrenocepto blockers
Class III
Prolongation of AP duration (usually K channel blockers)
Class IV
Ca channel blockers
Class I
MoA
Block fast Na channels (Phase 0)
Actions depend on HR and membrane potential
(Faster HR have less diastolic resting time, less time for drug to dissociate, more Na channels are blocked)
Can also have effects on K channels (APD)
Class IA
Intermediate kinetics, inc. APD
Procainamide
Quinidine
Disopyramide
Class IB
Fast kinetics, dec. APD
Lidocaine
Mexiletine
Class IC
Slow kinetics, does not change APD
Flecainidine
Propafenone
Procainamide
Class IA
Intermediate kinetics, inc. APD
Slows upstroke of AP, prolonges QRS, depressed SA and AV nodes
Procainamide Indications
Atrial and ventricular arrhythmias
2nd/3rd line drug for ventricular arrhythmias after acute MI (lidocain and amiodarone first)
Procainamide
Pharmacokinetics
IV, IM, PO
NAPA metabolite
Elimination via liver and kidney (NAPA)
1/2life 3-4 hours
Procainamide
Adverse Effects/toxicity
Anticholinergic effects, hypotension Torsade de pointes (NAPA!) Lupus erythematousus (long term)
Quinidine
Class IA
Intermediate kinetics, inc. APD
Similar action and indications to procainamide
Rarely used because cardiac and other severe effects greater than procainamide
Cinchonism: headache, dizziness, tinnitus
Lidocaine
Class IB
Fast kinetics, dec. APD
Use/state dependent
Depression of conduction in ischemic cells
Lidocaine
Indications
Arrhythmias after MI
First choice drug for v.tach and v.fib after cardioversion
PROPHYLACTIC TX NOT RECOMMENDED
Lidocaine
Pharmacokinetics
IV ONLY
First pass metabolism (cannot be taken orally)
Half-life 1-2 hours
Lidocaine
Adverse effects/toxicity
Least cardiotoxic of the class I Hypotension (large doses may affect cardiac contractility) Neurologic SE: local anesthetic properties, paresthesia, tremors, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions
Mexiletine
Class IB Fast kinetics, dec. APD Orally active lidocaine Half-life: 8-20 hours Off-label use: chronic pain in diabetic neuropathy/nerve injury (because of its loacl anesthetic properties)
Flecainide
Class IC
Slow kinetics, similar APD
Blocks K and Na channels
No anti-cholinergic effects
Flecainide
Indications
Supraventricular arrhythmias in patients with normal hearts
Flecainide
Pharmacokinetics
Well absorbed
Half-life 20 hours
Eliminted via liver and kidney
Fleicainide
Adverse effects/toxicity
Do not give to patient with ventricular tachyarrhythmias, MI, ventricular ectopy
Propafenone
Class IC
Blocks K and Na channels
Structurally similar to propranol, thus weak B-blocking
Propafenone
Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
Propafenone
Pharmacokinetics
PO
Half-life 5-7 hours
Liver elimination
Propafenone
Adverse effects/toxicity
Similar to flecainide (arrhythmogenic)
Sinus bradycardia/bronchospasm (B-blockade)
Metallic taste
Constipation
Class II
MoA
Inhibit normal sympathetic effects that act through B-adrenoceptors
Reduce Hr
Decrease intracellular Ca
Decrease pacemaker currents (SA node)
Reduce conduction velocity
Decrease catecholamine induced DAD and EAD mediated arrhythmias
Non-selective
B1 and B2
Propranolol
Sotalol
Timolol
Cardioselective
B1
Esmolol
Acebutolol
B-blocker
Indications
Prevention of infarction/death after MI Exercise-induced arrhythmias A. fib A. flutter AV nodal reenty
B-Blocker
Adverse Effects
Bradycardia
Reduced exercise capacity
Heart failure
Hypotension
AV block (contraindicated in bradycardia and partial AV block)
Bronchospasm (contraindicated in asthma and COPD)
Masks tachy in hypoglycemia (risk for diabetics)
Class III
MoA
Block K currents in phase 3 repolarization
QT prolongation
Enhance inward current (Na channels)
Delayed repolarization leads to AP prolongation
Reverse use/state dependence: least effects at fast heart rates, strong effects at low (risk torsades)
Amiodarone
MoA
Class III Structural analogue of thyroid hormone Prolong AP Blocks K, Na, Ca, inhibits B-receptors Prolongs refractory Slows reduction Slow sinus rhythm
Amiodarone
Indications
Oral: v.tach or v. fib not treatable by other drugs, a.fib (maintains sinus)
IV: 1ST CHOICE for out-of-hospital cardiac arrest, halting v.tach or v.fib
Amiodarone
Pharmacokinetics
IV or PO
Hepatic metabolization
Complex half life (stays in body for a while)
Lipophilic, accumulates in organs (heart, lung, liver, cornea)
Amiodarone
Adverse Effects
Bradycardia and heart block in SA/AV node disease Pulmonary toxicity (fibrosis) Hepatic toxicity Photodermatitis (skin discoloration) Cornea microdeposits Blocks conversion of T4 to T3 (iodine) Hypo and hyperthyoridisms
Dronedarone
Class III
Structural analogue of amiodarone
Altered to reduce thyroid effects
Dronedarone
Indications
A.fib
A. flutter
CONTRAINDICATED in severe/recently decompensated heart failure
Class VI
MoA
Ca channel blockers (vascular smooth muscle, cardiac myocytes, SA/AV nodes)
Ca influx is required for smooth muscle and cardiomyocyte contraction and phase 0 depolarization
Class IV
Dihydropyridines class
Nifedipine
Nitrendipine
High vascular selectivity
Used for hypertenstion
Class IV
Non-dihydropyridines
Benzothiazepine (Diltiazem): intermediate selectivity, used for hypertension, angina pectoris, arrhythmia
Pheylalkylamine (Verapamil): high cardiac selectivity, used for angina pectoris and arrhythmia
Verapamil
Class IV Ca channel blockers Blocks activated/inactivated Ca channels in heart Use/state-dependent action Major effects in slow-response tissues (SA/AV node) Directly slows AV Increases AV node refractoriness Slow SA node automaticity Lowers HR and increases PR interval
Verapamil
Indications
Supraventricular arrhythmias (drug of choice) Re-entry arrhythmias/tachycardias involving the AV node Slows ventricular rate in a.flutter/fib Makes everything slower because AV conduction is delayed
Verapamil
Pharmacokinetics
Extensively metabolized by liver
Half-life: 7 hours
Verapamils
Adverse Effects
Vasodilation
Negative inotropic effects
Constipation, nervousness, peripheral edema
CONTRAINDICATED in v.tach or LV dysfunction(will cause hypotension and fibrillation)
AV nodal disease (will cause AV block)
B-Blockers (will cause heart blocks)
Adenosine
Endogenous purine nucleoside Acts via GPCR Increases K conductance (hyperpolarization) Inhibits cAMP- Ca currents Atrial tissues Similar actions to acetylcholine Slows AV node conduction, increases AV node refractoriness PRODUCES TRANSIENT CARDIAC ARREST
Adenosine
Indications
DRUG OF CHOICE FOR SUPRAVENTRICULAR TACHYCARDIA TO SINUS RHYTHM
Adenosine
Adverse Effects
Flushing SOB Sinus bradycardia Sinus pauses AV block Hypotension
Adenosine
Pharmacokinetics
Half-life of seconds
Rapid IV bolus
Less effective with theophylline/caffeine
Potentiated by dipyridamole
A.fib/Supraventricular Tachycardia
Conversion to Sinus Rhythm
Adenosine/Amiodarone/Fecainide
A.fib/Supraventricular Tachycardia
Maintenance of Sinus Rhyhtm
Amiodarone/Dronedarone
Flecainide/Propafenone
A.fib/Supraventricular Tachycardia
Ventricular Rate Control
Diltiazem/Verapamil
Propranolol/Esmolol
Ventricular Tachycardia without Heart Disease
Amiodarone
Lidocaine
