Antiarrhythmic Drugs

Vaughan Williams Class Examples Function Therapeutic uses Adverse effect

Classification
Class I : Class IA -Quinidine -Large block of open Na⁺ and K⁺ -Broad spectrum of anti- Non cardiac:
Na⁺ channel  produces α blocker and -Effect on AP: arrhythmic effects -GI symptoms(nausea, abdominal
blocker vagal inhibition  Na⁺ blockage: slow AP in fast -clinically available but pain. diarrhoea)
 80% bound to plasma response tissues, prolong the infrequently used -Immunological
protein QRS duration (↑QRS). ↑ -Toxicity quite significant reaction(thrombocytopenia)
 potent inhibitor of threshold for excitability and ↓ -Cinchonism(headache, tinnitus)
hepatic CYP2S6 automaticity Cardiac:
 K⁺ blockage: prolong refractory -marked QT-interval prolongation
period, ↑QT -Torsade de pointes
-Prolong APD -marked hypotension
-sinus tachycardia
-Procainamide -Hypotension and marked slowing
 Oral and IV forms conduction
 Eliminated by: -nausea
-renal excretion of -torsades de pointes
unchanged drug -Lupus syndrome
-hepatic metabolism
Class IB Lignocaine -Blocks cardiac open Na⁺ channel but -Treatment of ventricular -Neurologic(most common)
 IV infusion(extensive 1st more to inactivated Na⁺ channels arrhythmias during myocardial  paraesthesia, tremor, nausea,
pass metabolism) -recovery from block is very rapid at ischaemia or due to digoxin light-headedness, hearing
 rapid onset and short normal resting potential toxicity disturbance, slurred speech,
duration of action -exerts greater effects in depolarized -Other uses: local anaesthesia convulsions
 elimination is slowed if and /or rapidly driven tissues -least cardiotoxic among Na⁺
hepatic blood flow ↓ -Slightly shorten APD due to blocking blockers
of small Na⁺ plateau current
Class IC -Flecainide -Potent Na⁺ channel blocker -Reduce automaticity by -hepatitis
-Propafenone -marked slow phase 0 fast increasing threshold potential -nausea
 mild ß-blocking depolarization and slow conduction -Minor effects on AP duration -emesis
properties in myocardial tissue and refractoriness -altered taste
-Prolong PR interval -Used in management of atrial
arrhythmias

Vaughan Williams Examples
Classification
Class II: Propranolol
ß-Adrenoceptor  Non-selective ß blocker
Antagonists  Exert Na⁺ channel
blocking effects in ↑
conc.
Metoprolol
 Selective ß₁- blocker
Class III Amiodarone
Action Potential  ↓Ca²⁺ current and blocks
Prolongation inactivated Na⁺ channels
 potently inhibit abnormal
automaticity and
↓conduction velocity
 drug interaction with
cimetidine and rifampicin
Sotalol
 Both K⁺ channel-blocking
and ß blocking activity
 renal excretion
Class IV -Verapamil
Calcium Channel  L-verapamil more potent
Blockers CCB than D-verapamil
 Oral, IV
 L-enantiomer undergoes
Antiarrhythmic Drugs
Function
-Reduce HR
-Prolong AV nodal refractoriness, slow AV
nodal conduction
-decrease intracellular Ca²⁺ overload
-Inhibit after depolarization-mediated
automaticity
-Prolong APD by blocking K⁺ channels
involved in cardiac repolarization
 increase in QT interval
 increase in refractoriness
-Block voltage-sensitive L type Ca²⁺
channels(Both open and inactivated), slow
conduction in SA and AV nodes
-AV nodal ERP is prolonged and AV
conduction is slowed(PR interval ↑)
-↓ Ca²⁺reduces after depolarization in PFs
Therapeutic uses
-terminate re-entrant arrhythmias that
involve the AV node control ventricular
response in atrial fibrillation or flutter
-Prevent arrhythmias and decreasing
mortality in post-MI
-broad spectrum efficacy against
supraventricular and ventricular
arrhythmias
-tachycardia associated with Wolff-
Parkinson-White syndrome
-oral therapy
 to maintain sinus rhythm in A-Fib or
Atrial flutter
 Patients with recurrent ventricular
tachycardia or fibrillation resistant
to other drug
-IV for acute termination of ventricular
tachycardia or fibrillation
-Prevention or management of
ventricular tachycardia and fibrillation
-maintenance of sinus rhythm in
patients with atrial fibrillation
-Oral verapamil prevent recurrence of
PSVT
-IV verapamil or diltiazem to terminate
PSVT; however adenosine is safer
-reduce ventricular rate in AF provided
they do not have Wolff-Parkinson-
Adverse effect
-Worsening of bronchospasm with
asthma
-negative inotropic effect
-bradycardia
-fatigue
-Proarrhythmic effects: torsades de
pointes
-Skin rash and slate-grey/bluish
discoloration in sun-exposed area
-thyroid abnormalities
-abnormal liver function test
-hepatitis
-corneal microdeposits
-fatal pulmonary fibrosis
-IV amiodarone
 Hypotension owing to
vasodilation and depressed
myocardial performance
-associated with ß blockade
-dysrhythmogenic effect
-Hypotension
-Constipation(oral verapamil)
-high doses: AV block or
suppression of SA node,
particularly when used in
combination with ß blockers,
 Antiarrhythmic Drugs

1st pass hepatic -Block Ca²⁺ channels in vascular smooth White disorder digoxin or drugs that inhibit the SA
metabolism muscle results in hypotension -Verapamil's negative inotropic effects and SV nodes
-Diltiezem limit its clinical usefulness in diseased
 1st pass metabolism hearts
Class V Adenosine -Activates Ach sensitive K⁺ channels and -IV to terminate Supraventricular -Short life
(Unclassified)  rapid bolus dose for causes membrane hyperpolarization thru' tachycardia (SVT) → largely replaced -Transient asystole(lasts< 5s)
efficacy stimulation of A₁(G-protein coupled) verapamil -flushing, sense of chest fullness
 elimination within adenosine receptors→ and dyspnoea, dizziness and
seconds, by carrier-  SA nodes: slows the rate of rise of the nausea
mediated uptake in most pacemaker potential→bradycardia -Drug interaction
cell types and  AV node(prolong ERP→ slowing  methylxanthines (theophylline,
subsequently metabolism conduction) caffeine) blocks adenosine
by adenosine deaminase -Also inhibits Ca²⁺ current→ ↑ AV nodal receptors
refractoriness and inhibits DADs elicited by  dipyridamole (vasodilators and
sympathetic stimulation antiplatelet) blocks nucleoside
uptake mechanism,
potentiating adenosine and
prolong its adverse effects
Magnesium sulphate