This document discusses sodium channel blockers and their mechanisms and effects. Sodium channel blockers increase the threshold for excitation, decrease conduction velocity, and increase refractoriness. They can either suppress or exacerbate arrhythmias depending on their effects on conduction and refractoriness. Common sodium channel blocking drugs include lidocaine, phenytoin, and mexiletine. Adverse reactions include decreased conduction and worsening of arrhythmias in some cases. The document also briefly discusses other classes of antiarrhythmic drugs like potassium channel blockers, calcium channel blockers, adenosine, and vernakalant.

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 150-
200 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