Antiarrhythmics

Question 1

Vaughan Williams classification

Answer 1

Class I: Membrane stabilizing drugs
Class Ia: Quinidine, disopyramide, procainamide (Na channel blockers)
Class Ib: Lidocaine, mexiletine, phenytoin (Na channel blockers- fast)
Class Ic: Flecainide, propafenone (Na channel blockers- slow)
Class II: β-adrenoceptor antagonists: propranolol, metoprolol
Class III: Increase action potential (AP) refractory period: amiodarone, bretylium, sotalol (K+ channel blockers)
Class IV: Calcium-channel blockers: verapamil, diltiazem
Others: Digoxin, adenosine, magnesium (direct nodal inhibition)

Question 2

Drugs with efficacy for Supraventricular arrhythmias

Answer 2

Digoxin, verapamil, adenosine

Question 3

Drugs with efficacy for ventricular arrhythmias

Answer 3

Lidocaine, phenytoin

Question 4

Drugs with efficacy for SV and ventricular arrhythmias

Answer 4

Amiodarone, beta blockers, disopyramide/ procainamide, flecainide

Question 5

Class 1- Na channel blockers

Answer 5

Lidocaine, phenytoin, flecanide

Reduce the phase 0 slope and the peak of the action potential

Question 6

Lidocaine

Answer 6

Used to treat ventricular arrhythmias and given IV. Reduced the rate of rise of phase 0, mediated by Na channel blockade.

SEs: Hypotension, bradycardia, arrhythmias.
CNS excitatory: agitation, tingling around mouth, headache, hyperaesthesia, tremor, dizziness, pupillary changes, psychosis, seizures
CNS depressant: drowsiness, slurred speech, confusion, LOC, resp depression

Contraindications:
1. 2nd/3rd degree heart block without a pacemaker
2. severe SA block
3. serious adverse reaction to lidocaine/amide LAs
4. concurrent treatment with quinidine, flecainide, disopyramide (class 1s)
5. Adams-stokes syndrome
6. WPW

Question 7

Flecainide

Answer 7

Treats many SVTs, including AF and WPW. Na channel blocker.

Avoid in structural heart disease/ ischaemic injury.

Narrow therapeutic index so monitor levels closely if given IV

SEs:
Arrhythmias (TdP)
Prolonged PR and widened QRS
Negative inotropic effect so use with caution if poor ejection fraction.

Question 8

Class 2, beta blockers

Answer 8

These agents act to decrease sympathetic activity on the heart, which reduces intracellular cAMP levels and hence reduces Ca2+ influx. These agents are particularly useful in the treatment of supraventricular tachycardias.

SEs: Hypotension, bradycardia, heart block, depression, sexual dysfunction, imapired glucose handling.

Question 9

Esmolol

Answer 9

Esmolol (Fig 1) is often given as an infusion at 50-200 mcg/kg/min. It can be used to manage hypertension, as well as the management of tachycardia in the perioperative period. It is irritant to veins and extravasation may lead to tissue necrosis. It has a short half-life due to being broken down by red cell esterases.

Contraindications to beta-blocker use include bradycardia, heart block and WPW. Care must be taken in those with disease of the airways (COPD, asthma) as beta-blockers can cause bronchoconstriction.

Question 10

Class 3- K+ channel blockers

Answer 10

Amiodarone, bretyllium, sotalol.

Prolong repolarisation by blocking K+ channels.

Exhibit reverse-use dependence i.e. their potency increases with slower heart rates and therefore improves maintenance of sinus rhythm.
Inhibiting potassium channels, slowing repolarisation, results in slowed atrial-ventricular myocyte repolarisation.

Class III agents have the potential to prolong the QT interval of the ECG, and may be proarrhythmic.

Question 11

Amiodarone

Answer 11

Used in both V and SV tachycardias. Should be given into a central vessel and diluted in 5% glucose (irritant).

300mg loading dose over 1hr followed by 900mg over 24 hours,

Side effects: ILD, thyroid dysfunction, abnormal liver enzymes, corneal micro-deposits and photosensitivity.

Long term- check TFTs and LFTs

Contraindications: pregnancy, bradycardia

Question 12

Class 4- Ca channel blockers

Answer 12

Verapamil, diltiazem.

Prevent influx of calcium through voltage sensitive slow (L) channels in the AV and SA node, slowing conduction and reducing automaticity. This shortens phase 2, the plateau.

SEs: constipation, dizziness, headache, redness, ankle oedema, bradycardia.

Can reduce the contractility of the heart. Use with caution in heart failure. Don’t use in WPW as it can precipitate VT.

Question 13

Adenosine

Answer 13

Class V.

Treat SVTs. Causes AVN blockade via specific adenosine-A receptors. Very shorts half life <10s and is taken up rapidly by RNCs. Can be used to differentiate between SVT and VT as it will resolve SVT but not VT.

SEs: diaphoresis, metallic taste, nausea, doom

CIs: asthma, decompensated HF, long QT syndrome

Question 14

Digoxin

Answer 14

Class V

Inhibits Na/K ATPase in the myocardium, raising intracellular Na levels. Also increased intracellular Ca levels which prolongs phase 4 and phase 0 of the cardiac AP.

Acts indirectly to increase the release of ACh at cardiac muscarinic receptors, slowing conduction and prolonging the refractory period in the AV node and the bundle of His.

Weak inotrope.

Side-effects: digoxin has a narrow therapeutic index and so levels must be monitored. Others include gynaecomastia, nauseas and yellow vision. Hypokalaemia can precipitate side-effects as potassium and digoxin act at the same receptors.

Digoxin toxicity causes a characteristic ECG appearance of ST depression, flat T waves and QT interval shortening