1. Na+ channel blocker:
Na+ channel block depends on: HR
Membrane potential
Drug specific physiochemical characteristic-  recovery
Blockade of Na+ channels results in:
Threshold for excitability is increased (more current)
Increase in pacing and defibrillation threshold
Decrease conduction velocity in fast response tissues
Increase QRS interval (due to conduction slowing in ventricles)
Some drugs tend to prolong PR interval- flecainide (possibly Ca2+ channel blockade)

2. Some sodium channel blockers shorten the PR interval (quinidine; vagolytic effect)
APD unaffected or shortened
Increase in threshold for excitation also decreases automaticity
Can also inhibit DAD/EAD
Delays conduction so can block re-entry
In some cases, it can exacerbate re-entry by delaying conduction
Shift voltage dependence of recovery of sodium channels from inactivated state to more negative potentials and so increases refractoriness
Net effect- whether it will suppress or exacerbate re-entry arrhythmia depends on its effect on both factors- conduction velocity and refractoriness

3. Most Na+ channel blockers bind to either open or inactivated state and have very little affinity for channels in closed state, drug binds to channels during systole & dissociates during diastole
ADRs:
Decrease in conduction rate in atrial flutter- slows rate of flutter and increases HR due to decrease in AV blockade
Especially common with quinidine due to its vagolytic property; also seen with flecainide and propafenone
Cases of ventricular tachycardia due to re-entrant rhythm following MI may worsen due to slowing of conduction rate
Slowing of conduction allows the re-entrant rhythm to persist within the circuit so that complicated arrhythmias can occur
Several Na+ channel blockers have been reported to exacerbate neuromuscular paralysis by d-tubocurarine

4. Na+ channel blockers lidocaine, phenytoin and mexiletine have only sodium channel blocking activity
Lidocaine blocks Na+ channels more in open than in inactive state
Phenytoin blocks them in inactivated state
Quinidine blocks Na+ channels in open state
It also has vagolytic and  blocking activity
Procainamide, disopyramide, propafenone block sodium channels in open state
Sotalol is a  blocker with Na+ channel blocking activity
Amiodarone and dronedarone block sodium channels in inactivated state and produce non-competitive blockade of  receptors

5. Phenytoin is an anti-epileptic drug that blocks sodium channels and is used for treatment of digitalis induced tachyarrhythmias
Reasons:
Does not aggravate AV block
Does not produce hypotension
It is a potent hepatic microsomal enzyme inducer
Toxicity- gum hyperplasia
Mexiletine is an oral analogueof lidocaine, does not undergo first pass metabolsm
It is preferred for treatment of ventricular arrhythmias associated with previous MI
Lidocaine, a local anaesthetic is given as i.v. loading dose of mg in 15 min followed by maintenance dose

6. Lidocaine is extensively metabolized in the liver so not given orally
Toxicity- drowsiness, convulsions, slurred speech, confusion, paresthesia
Quinidine, due to vagolytic action, can potentiate ventricular tachycardia if given in the presence of rapid heart rate
In addition to antiarrhythmic effect, it has antimalarial, antipyretic and skeletal muscle relaxant actions
Procainamide is a derivative of procaine, a LA with actions similar to that of quinidine

7. Quinidine is contraindicated in cases of:
AV block (because it slows conduction)
QT prolongation (already slow conduction is there)
CHF and hypotension due to its negative inotropic effects
Digitalis intoxication and hyperkalemia that potentiate the decrease in conduction velocity by quinidine
Digitalis toxicity because it has negative inotropic effects so antagonizes positive inotropic effects of digitalis
Myasthenia gravis (may be aggravated due to its muscle relaxant property
Atrial flutter & fibrillation (rapid HR)- quinidine can potentiate ventricular tachycardia due to its vagolytic action on AV node

8. ADRs of quinidine:
Diarrhoea
Reversible thrombocytopenia due to formation of plasma protein-quinidine complex which forms antibodies against circulating platelets
Quinidine syncope- loss of consciousness due to ventricular arrhythmias)
Large doses (toxicity) may cause cinchonism- tinnitus, headache, nausea, blurring of vision and vertigo
Interactions:
Increases plasma levels of digoxin & precipitates its toxicity
Enzyme inducers facilitate its metabolism-  plasma concentration
Mg hydroxide & CaCO3 elevate its plasma concentration

9. K+ Channel blockers:
Prolong APD (QT interval) and reduces automaticity
Increase in APD also increases refractoriness
Effective in treating re-entrant arrhythmias
Reduce energy requirement for defibrillation
Inhibit ventricular arrhythmias in cases of myocardial ischemia
Many K+ channel blockers also have  blocking activity also like sotalol
Disproportionate prolongation of APD can result in torsaides de pointes, specially when basal HR is slow

10. Drugs included in this group are amiodarone, dronedarone, ibutilide, dofetilide, bretylium and sotalol
They prolong APD and ERP without affecting phase 0 depolarization or resting membrane potential
Amiodarone is an iodine containing analogue of thyroid hormone
It is highly lipohilic drug
It blocks inactivated Na+ channels, Ca2+ channels and K+channels
Bretylium is a adrenergic neurone blocker with K+ channel blocking activity
It was introduced as antihypertensive –obsolete now
Used i.v. for treatment of resistant ventricular arrhythmias

11. CCBs:
Major effect on nodal tissues
Verapamil, diltiazem and bepridil cause slowing of HR, nifedipine and other dihydropyridines reflexly increase HR
Decrease AV nodal conduction so PR interval increases
AV nodal block occurs due to decremental conduction and increase in AV nodal refractoriness
DAD leading to ventricular tachycardia respond to verapamil
Verapamil and diltiazem are recommended for treatment of PSVT
Bepridil increases APD in many tissues and can exert antiarrhythmic action in atria and ventricles but it use is associated with increased incidence of torsades de pointes- rarely used

12. Verapamil and diltiazem block both open and inactivated L-type of calcium channels
They decrease the rate of phase 4 depolarization in SA and AV nodes decrease conduction in AV node
Adenosine: Naturally occuring neucleotide
Administered as rapid i.v. bolus for acute termination of re-entrant supraventricular arrhythmias
Also used to produce controlled hypotension for some surgical procedures
Effects are mediated through G-protein coupled adenosine receptors
It activates ACh sensitive K+ current in atrium, SA and AV nodes
Shortens APD, hyperpolarization and slowing of automaticity

13. It also reduces Ca2+ currents and increases nodal refractoriness thereby acts as antiarrhythmic
t½ is in seconds
Magnesium sulphate: to terminate torsaides de pointes, mechanism unknown

14. Vernakalant:
Blocks several ion channels in atria
Mainly blocks ultra rapidly acting delayed rectifier K+ channels
Also blocks other K+ currents, Na+ current and L-type of Ca2+ current
Does not significantly affect ventricular refractoriness
Used for treatment of atrial fibrillation as i.v. infusion