ANTIARRHYTHMIC DRUGS

Introduction
•Arrhythmias (also called dysrhythmias) are defined as any rhythm that is not normal
sinus rhythm
•Cardiac arrhythmias are the most common cause of death in patients with a myocardial
infarction or terminal heart failure.
•They are also the most serious manifestation of digitalis toxicity & are often assoc with
anesthesia, hyperthyroidism, & electrolyte disorders.

Nature of Arrhythmias
•Normal electrical cardiac function (normal sinus rhythm, NSR) is dependent on generation of
an impulse in the normal sinoatrial (SA) node pacemaker & its conduction through the
atrial muscle, through the atrioventricular (AV) node, through the Purkinje conduction
system, to the ventricular muscle (Fig 1)
FIG1: normal cardiac electrical activity
•Normal pacemaking and conduction require normal action potentials (which are dependent
on Na+, Ca2+, & K+ channel activity) under appropriate autonomic control.

Causes of arrhythmias

•Most arrhythmias arise either from either

1. Distortion in impulse generation (abnormal automaticity) or from
2. A defect in impulse conduction.

1. Abnormal automaticity
•In contrast to skeletal muscle, which contracts only when it receives a stimulus, the heart
contains specialized cells that exhibit automaticity (i.e, they intrinsically generate
rhythmic action potentials in the absence of external stimuli)
•These “pacemaker” cells differ from other myocardial cells in showing a slow, spontaneous
depolarization during diastole (phase 4), caused by an inward positive current carried by
sodium & calcium ions
•This depolarization is fastest in the sinoatrial (SA) node (the normal initiation site of the
action potential = pacemaker)
•The depolarization decreases throughout the normal conduction pathway through the AV
node to the bundle of His and the Purkinje system.
•The SAN shows the fastest rate of phase 4 depolarization
•There4, it normally sets the pace of contraction for the myocardium
 •If cardiac sites other than the SAN show enhanced automaticity, they may generate
competing stimuli, and arrhythmias may arise
•Most of the antiarrhythmic agents suppress automaticity by blocking either Na + or Ca2+
channels to reduce the ratio of these ions to K+.
•This decreases the slope of phase 4 (diastolic) depolarization &/or raises the threshold
of discharge to a less negative voltage.
•Antiarrhythmic drugs cause the frequency of discharge to decrease.
•This effect is more pronounced in cells with ectopic pacemaker activity than in normal cells

2.Abnormalities in impulse conduction

•Impulses from higher pacemaker centers are normally conducted down pathways that
bifurcate to activate the entire ventricular surface (Fig 1 & Fig 2A)

•A phenomenon called reentry can occur if a unidirectional block caused by myocardial

injury or a prolonged refractory period results in an abnormal conduction pathway (Fig
2B)

•Reentry is the most common cause of arrhythmias, & it can occur at any level of the
cardiac conduction system
•This short-circuit pathway results in reexcitation of the ventricular muscle, causing
premature contraction or sustained ventricular arrhythmia.
•Antiarrhythmic agents prevent reentry by slowing conduction (class I drugs) &/or increasing
the refractory period (class III drugs)
as a result they convert a unidirectional block into a bidirectional block

Overview of Antiarrhythmic drugs

•These drugs can modify impulse generation and conduction:
a. To prevent arrhythmias from occurring or
b. To reduce symptoms associated with arrhythmias.
•Unfortunately, many of the antiarrhythmic agents are known to have dangerous
proarrhythmic actions (i.e they may cause arrhythmias)
•Inhibition of K+ channels (typically a class III activity) widens the action potential and can,
there4, prolong the QT interval
•If prolongation is excessive, these drugs increase the risk of developing life-threatening
ventricular tachyarrhythmias (torsades de pointes).
•The commonest cause of QT prolongation is drug-induced, e.g by macrolide antibiotics &
antipsychotics

•Drugs s.a cisapride & terfenadine were withdrawn from the market because of severe and
fatal arrhythmias
•Other conditions that may contribute to QT prolongation include:
i. Ischemia
ii. Hypokalemia
iii. Genetic
disorders
•Caution is required when either
a. Combining drugs with additive effects on the QT interval or
b. When giving QT-prolonging antiarrhythmic drugs with drugs known to
inhibit their metabolism.
•In addition, Most antiarrhythmic drugs have very low therapeutic indices
•There4 when possible, nondrug therapies (cardioversion, pacemakers,
ablation, implanted defibrillators) are used
•The benefit of antiarrhythmic drugs must always be compared to the potential for serious
adverse effects (AEs) or drug interactions (DIs)

CLASSIFICATION OF ANTIARHYTHMIC DRUGS

•They fall into five major groups or classes

•The classification is based on their predominant effects on the action potential (Fig 3)
However, many drugs have actions relating to more than one class or may have
active metabolites with a different class of action.
 •The antiarrhythmic agents are usually classified using a system based on the
channel or receptor involved.
•This system specifies 4 groups or classes, usually denoted by the numerals 1
through 4, plus a miscellaneous group (see fig 3 & Table 1)

Sodium channel blockers

1. Beta-adrenoceptor blockers
2. Potassium channel blockers
3. Calcium channel blockers
4. The miscellaneous group

1. CLASS I ANTIARRHYTHMIC DRUGS (LOCAL ANESTHETICS)

Classification
•They are subdivided on the basis of their effects on action potential (AP)
duration into 3 subgroups, 1A, 1B & 1C
a. Class 1A antiarrhythmic drugs
•Disopyramide
•Procainamide
•Quinidine

b. Class 1B antiarrhythmic drugs

•Lidocaine
•Mexiletine

c. Class 1C antiarrhythmic drugs

•Flecainide
•Propafenone
General MoA of Class I antiarrhythmic drugs

•The Class I drugs act by blocking voltage-sensitive sodium (Na+) channels

•All grp 1 drugs reduce both phase 0 & phase 4 Na+ currents (wavy lines) in
susceptible cells (Fig 4)
•They slow conduction in ischemic & depolarized cells
•They also slow or abolish abnormal pacemakers wherever these processes
depend on sodium channels.
 •They bind to their receptors much more readily when the channel is open or
inactivated than when it is fully repolarized and resting.
•Therefore, they block channels in abnormal tissue more effectively than
channels in normal tissue.
•They are use dependent or state dependent in their action (ie, they selectively
depress tissue that is frequently depolarizing, eg, during a fast tachycardia
or tissue that is relatively depolarized during rest, eg, by hypoxia).

a. CLASS IA ANTIARRHYTHMIC DRUGS

Classification
•Quinidine is the prototype class IA drug.
•Other agents in this class include procainamide and disopyramide

•Amiodarone is often classified in class 3, but it also has typical class 1A actions.

MoA class IA drugs

•Group 1A agents prolong the AP
•They affect both atrial & ventricular arrhythmias.
•They block INa (sodium channel) & therefore slow conduction velocity in the atria,
Purkinje fibers, and ventricular cells.

•At high doses they may slow AV conduction.

•Amiodarone has similar effects on sodium current (INa block) & has the greatest AP-
prolonging effect (IK block).

PK of class IA drugs

•Quinidine sulfate or gluconate is rapidly & almost completely absorbed after oral
admin
•It undergoes extensive metabolism primarily by the hepatic CYP 3A4 isoenzyme,
forming active metabolites.

•Procainamide is available in an IV formulation only

•It has a relatively short duration of action of 2 - 3 hrs.
•A portion of procainamide is acetylated in the liver to N-acetylprocainamide
(NAPA), which prolongs the duration of the action potential.
•There4, NAPA has properties and side effects of a class III drug.
•NAPA is eliminated via the kidney, and dosages of procainamide may need to be
adjusted in patients with renal failure.
•Disopyramide is well absorbed after oral admin.
•It is metabolized in the liver to a less active metabolite & several inactive
metabolites.
•It is a substrate of CYP3A4.
•~ half of the drug is excreted unchanged by the kidneys.
 Clinical use of class 1A antiarrhythmic drugs

•Procainamide can be used in all types of arrhythmias. However, atrial and

ventricular arrhythmias are most responsive.

•Quinidine and disopyramide have similar effects but are used much less frequently
•Procainamide is also commonly used in arrhythmias during the acute phase of
myocardial infarction

•NB: electrical cardioversion or defibrillation & amiodarone have mostly replaced

class 1 drugs in clinical use.

Adverse effects

•Quinidine causes cardiac depression, gastrointestinal upset &

autoimmune reactions (eg, thrombocytopenic purpura).
•Large doses of quinidine may induce symptoms of cinchonism (e.g, blurred vision,
tinnitus, headache, disorientation, & psychosis).

•IV admin of procainamide may cause hypotension & a reversible syndrome similar to
SLE
•Disopyramide has the most anticholinergic adverse effects of the class IA drugs (e.g,
dry mouth, urinary retention, blurred vision, & constipation).
•It may also precipitate heart failure
•All group 1A drugs may precipitate new arrhythmias.
•Torsades de pointes is particularly associated with quinidine and other drugs that
prolong AP duration (except amiodarone).

Drug interactions & caution

•Drug interactions are common with quinidine which is an inhibitor of both CYP2D6
and Pglycoprotein.
•Quinidine reduces the clearance of digoxin and may increase the serum concentration
of the glycoside significantly.
•Both quinidine & disopyramide should be used with caution with potent inhibitors of
CYP3A4
•Hyperkalemia usually worsens the cardiac toxicity of group 1
drugs.
Rx of overdose of class IA drugs
i. Sodium lactate (to reverse drug-induced arrhythmias) and

ii. Pressor sympathomimetics (to reverse druginduced hypotension) if indicated.

b. CLASS IB ANTIARRHYTHMIC DRUGS

Classification
•Lidocaine is the prototype 1B drug
•It is used exclusively by the IV or IM routes.
•Mexiletine is an orally active 1B agent.
MoA
•In addition to sodium channel blockade, grp 1B drugs shorten phase 3 repolarization
and decrease the duration of the action potential ( fig 4)
•These drugs selectively affect ischemic or depolarized Purkinje and ventricular tissue
•However, they have little effect on atrial tissue

•The class IB agents rapidly associate and dissociate from sodium channels.
•There4, their actions are manifested when the cardiac cell is depolarized or firing
rapidly.
•They have little effect on normal cardiac cells
•There4, they have little effect on the ECG (Table 1 ).
•Phenytoin, an anticonvulsant is not a true local anesthetic
•It is sometimes classified with the group 1B agents because it can be
used to reverse digitalis-induced arrhythmias.
•It resembles lidocaine in lacking significant effects on the normal ECG.
PK of class IB drugs
•Lidocaine is given IV
- However, IM administration is also possible.

- It is never given orally becos it has a very high first-pass effect and its
metabolites are potentially cardiotoxic.

- It is dealkylated to two less active metabolites, primarily by CYP1A2 with a

minor role by CYP3A4.
- Lidocaine should be monitored closely when given in combination with drugs
affecting these CYP isoenzymes.
- Lidocaine is highly extracted by the liver
- There4, drugs that lower hepatic blood flow (e.g β-blockers) may require
lidocaine’s dose adjustment.

•Mexiletine is well absorbed after oral admin. •It is metabolized in the liver primarily by
CYP2D6 to inactive metabolites & excreted mainly via the biliary route

Clinical use of class 1B antiarrhythmic drugs

•Lidocaine is used in acute ischemic ventricular arrhythmias, e.g, after myocardial

infarction.

- Amiodarone has displaced lidocaine for Rx of ventricular fibrillation or pulseless

ventricular tachycardia (VT)
- However, lidocaine may be used as an alternative.
 - Lidocaine may also be used in polymorphic VT or in combination with
amiodarone for VT storm.
- Lidocaine does not markedly slow conduction
- There4, it has little effect on AV junction arrhythmias or atrial arrhythmias
(unless caused by digitalis)
•Mexiletine is used for chronic Rx of ventricular arrhythmias, often in combination with
amiodarone

Adverse effects of class IB drugs

•Lidocaine has a fairly wide therapeutic index.

- It shows little impairment of left ventricular function and has no negative
inotropic effect.
- CNS effects include nystagmus (early indicator of toxicity), drowsiness, slurred
speech, paresthesia, agitation, confusion, and convulsions, which often limit the
duration of continuous infusions.
•Mexiletine has a narrow therapeutic index
- There4 caution should be used when administering the drug with inhibitors of
CYP2D6.
- Nausea, vomiting, and dyspepsia are its most common adverse effects.
- Lidocaine and mexiletine occasionally cause Allergy (usually rashes but may
extend to anaphylaxis).
- They may also precipitate arrhythmias
- However, this is much less common than with group 1A drugs.
- Hyperkalemia increases their cardiac toxicity.

c. CLASS 1C ANTIARRHYTHMIC DRUGS

Classification
•Flecainide is the prototype group 1C drug.
•Propafenone is another member of the group
MoA
•Flecainide suppresses phase 0 upstroke in Purkinje and myocardial fibers (Fig 4 ).
- This causes marked slowing of conduction in all cardiac tissue, with a minor
effect on the duration of the action potential and refractoriness.
- Automaticity is reduced by an increase in the threshold potential, rather than a
decrease in slope of phase 4 depolarization.
 - Flecainide also blocks potassium channels leading to increased action potential
duration, more than propafenone does.
•Propafenone, like flecainide, slows conduction in all cardiac tissues but does
not block potassium channels
- The class 1C drugs slowly dissociate from resting sodium channels and
show prominent effects even at normal heart rates
- They have no effect on ventricular AP duration or the QT interval.
- They increase the QRS duration of the ECG.
PK of class IC drugs
•Flecainide is absorbed orally
•It is metabolized by CYP2D6 to multiple metabolites.
•The parent drug and metabolites are mostly eliminated renally, and dosage
adjustment may be required in renal disease.

•Propafenone is metabolized to active metabolites primarily via CYP2D6, & also by

CYP1A2 & CYP3A4.

•The metabolites are excreted in the urine and the stool.

Clinical use of class 1C antiarrhythmic drugs

•Flecainide is effective in both atrial & ventricular arrhythmias

•It is used in
a. The maintenance of sinus rhythm in atrial flutter or fibrillation in
patients without structural heart disease (such as left ventricular
hypertrophy, heart failure, atherosclerotic heart disease) &
b. Rx of refractory ventricular arrhythmias.
•Use of propafenone is restricted mostly to atrial arrhythmias e.g
a. Rhythm control of atrial fibrillation or flutter &
b. Paroxysmal supraventricular tachycardia prophylaxis in
patients with AV reentrant tachycardias.
The latter indication takes advantage of the β-blocking properties
of propafenone
Adverse effects of class IC drugs

•Flecainide is generally well tolerated, with blurred vision, dizziness, and nausea
occurring most frequently.

•Flecainide & its analogs are more likely than other antiarrhythmic drugs to
worsen or precipitate arrhythmias (proarrhythmic effect).

•It has a negative inotropic effect and can worsen chronic heart failure.
•Propafenone has a similar adverse effect profile
•In addition it may also cause bronchospasm due to its β-blocking effects.
•It should there4 be avoided in patients with asthma.
 •Propafenone is also an inhibitor of Pglycoprotein.
•Group 1C drugs also cause local anesthetic-like CNS toxicity.
Caution with class IC drugs

i. Hyperkalemia increases the cardiac toxicity of Group 1C drugs.

ii. Both drugs should be used with caution with potent inhibitors of
CYP2D6

2. CLASS 2 ANTIARRHYTHMICS (BETA BLOCKERS)

Classification
a. Metoprolol
b. Atenolol
c. Esmolol
d. Propranolol
MoA & Effects

•Metoprolol, Propranolol and esmolol are prototypic antiarrhythmic β blockers.

•Their MoA in arrhythmias is primarily cardiac βadrenoceptor blockade and reduction
in cAMP
•This results in the reduction of both sodium and calcium currents and the suppression
of abnormal pacemakers.
•The AV node is particularly sensitive to β blockers
•Group 2 drugs usually prolong the PR interval (see Table 1).
•They diminish phase 4 depolarization and, there4:
a. Depress automaticity
b. Prolong AV conduction &
c. Decrease heart rate and contractility
•These drugs may have some direct local anesthetic (sodium channel-blocking)
effect in the heart, but this is probably rare at the concentrations achieved
clinically.
•Sotalol and amiodarone are generally classified as group 3 drugs
•However, they also have group 2 β-blocking effects.

PK of class 2 drugs
•Metoprolol is extensively metabolized in the liver primarily by CYP2D6
- It penetrates into the CNS (less than propranolol, but more than atenolol

•Esmolol has a fast onset of action and a short half-life, making it ideal for acute
situations and also limiting its adverse effect profile.

- It is rapidly metabolized by esterases in red blood cells.

Drug interactions
•There are no PK drug interactions with the class 2 antiarrhythmic drugs

Clinical use of class 2 antiarrhythmic drugs

•Metoprolol is the β-blocker most widely used in the Rx of cardiac arrhythmias.

- Compared to nonselective β-blockers, such as propranolol, it reduces the risk of
bronchospasm.

•Esmolol is used IV in acute arrhythmias that occur during surgery or emergency

situations.
•Class II agents are useful in the Rx of tachyarrhythmias caused by increased
sympathetic activity.
•They are also used for atrial flutter and fibrillation and for AV nodal reentrant
tachycardia.

•Propranolol, metoprolol, and timolol are commonly used as prophylactic drugs to

prevent life-threatening ventricular arrhythmias following a myocardial infarction.

Caution

•Patients with arrhythmias are often more prone to β-blocker-induced depression of

cardiac output than patients with normal hearts
•However, cautious use of these drugs reduces progression of chronic heart failure and
reduces the incidence of potentially fatal arrhythmias in this condition.

3. CLASS 3 ANTIARRHYTHMICS (POTASSIUM CHANNEL BLOCKERS)

Classification
a. Amiodarone
b. Dofetilide
c. Dronedarone
d. Ibutilide
e. Sotalol
•Dofetilide and ibutilide are typical group 3 drugs.

•Sotalol is a chiral compound (ie, it has 2 optical isomers).

•One isomer is an effective β blocker, and both isomers contribute to the
antiarrhythmic action.
•The clinical preparation contains both isomers.
•Amiodarone is usually classified as a group 3 drug because it blocks K+ channels and
markedly prolongs AP duration as well as blocking sodium channels.

•Dronedarone is an amiodarone analog

 MoA of class 3 antiarrhythmic drugs
•The group 3 drugs prolong the AP duration by blockade of IK potassium channels,
primarily IKr, that are responsible for the repolarization of the AP (Fig 5).
•There4, they diminish the outward potassium current during repolarization of cardiac
cells.
•AP prolongation results in an increase in effective refractory period and reduces the
ability of the heart to respond to rapid tachycardias.

•Group 3 drugs do not alter phase 0 of depolarization or the resting membrane

potential
•Sotalol, ibutilide, dofetilide, and amiodarone (and group 1A drugs)
produce this effect on most cardiac cells
•The action of these drugs is, therefore, apparent in the ECG as an increase in QT
interval (Table 1).

a. Amiodarone

MoA
•It contains iodine and is related structurally to thyroxine.

•It has a broad spectrum showing class I, II, III, and IV actions
•It blocks sodium, calcium, and potassium channels, β adrenoceptors & α-receptors
•However, Amiodarone’s dominant effect is prolongation of the action potential
duration and the refractory period by blocking K+ channels.
PK

•Amiodarone is incompletely absorbed after oral administration.

•It is unusual in having a prolonged half-life of several weeks, and it distributes
extensively in adipose tissue.
•Full clinical effects may not be achieved until months after initiation of Rx, unless
loading doses are used.
Clinical use

•Amiodarone is useful in most types of arrhythmias and is considered the most

efficacious of all antiarrhythmic drugs

•Despite its adverse effect profile, amiodarone is the most commonly used
antiarrhythmic
•It is effective in the Rx of severe refractory supraventricular and
ventricular tachyarrhythmias.
•It has been a mainstay of therapy for the management of atrial fibrillation or flutter.
•It is also thought to be the least proarrhythmic of the class I and III
antiarrhythmic drugs
Adverse effects
•Amiodarone shows a variety of toxic effects, including pulmonary fibrosis,
neuropathy, hepatotoxicity, microcrystalline corneal deposits, optic neuritis, blue-
gray skin discoloration, thyroid dysfunction (hyper- or hypothyroidism),
paresthesias, tremor,
•Amiodarone rarely causes new arrhythmias, perhaps because it blocks calcium,
sodium and potassium channel as well as β receptors
•Use of low doses and close monitoring reduce toxicity, while retaining clinical efficacy.
Drug interactions
•Amiodarone is subject to numerous drug interactions, becos it is metabolized by
CYP3A4 and is also an inhibitor of CYP1A2, CYP2C9,
CYP2D6, and P-glycoprotein

b. Dronedarone

•It is an amiodarone derivative, which is less lipophilic, has lower tissue accumulation,
and has a shorter serum half-life than amiodarone.
•It does not have the iodine moieties that are responsible for thyroid dysfunction
associated with amiodarone.
•Like amiodarone, it has class I, II, III, and IV actions.
•Currently, dronedarone is used to maintain sinus rhythm in atrial fibrillation or flutter,
but it is less effective than amiodarone.
•Dronedarone has less adverse effects than amiodarone but may still cause liver
failure.
•It is contraindicated in those with symptomatic heart failure or permanent atrial
fibrillation due to an increased risk of death.

4.CLASS IV ANTIARRHYTHMIC DRUGS (CALCIUM L-TYPE CHANNEL BLOCKERS)

Classification
•These are the nondihydropyridine calcium channel blockers verapamil and diltiazem
 MoA
•Although voltage- sensitive calcium channels occur in many different tissues, the
major effect of calcium channel blockers is on vascular smooth muscle and the
heart.
•Verapamil shows greater action on the heart than on vascular smooth muscle, and
diltiazem is intermediate in its actions.

•In the heart, verapamil and diltiazem bind only to open depolarized voltage-sensitive
channels, thus decreasing the inward current carried by calcium.
•They prevent repolarization until the drug dissociates from the channel, resulting in a
decreased rate of phase 4 spontaneous depolarization.
•These drugs are therefore use-dependent.
•They also slow conduction in tissues that are dependent on calcium currents, such as
the AV and SA nodes (Fig 6).
•AV conduction velocity is decreased, and effective refractory period and PR interval
are increased by these drugs (see Table 1 below).
NB:
•Nifedipine and the other dihydropyridines are not useful as antiarrhythmics, probably
because they decrease arterial pressure enough to evoke a compensatory
sympathetic discharge to the heart.
•The latter effect facilitates rather than suppresses arrhythmias
PK of Class IV antiarrhythmic drugs
•Both drugs are metabolized in the liver by CYP3A4.
•Dosage adjustments may be needed in patients with hepatic dysfunction.
•Both agents are also inhibitors of CYP3A4, as well as substrates and inhibitors of
Pglycoprotein.
•They are there4 subject to many drug interactions.
Clinical use of Class IV antiarrhythmic drugs

•They are more effective against atrial than against ventricular arrhythmias.
•They are useful in treating reentrant supraventricular tachycardia and in
reducing the ventricular rate in atrial flutter and fibrillation

5. MISCELLANEOUS ANTIARRHYTHMIC DRUGS

Classification
a. Adenosine
b. Digoxin
c. Magnesium sulfate
d. Potassium Ion

a. Adenosine
•It is a naturally occurring nucleoside which is a normal component of the body
 MoA
•At high doses given as an IV bolus, it has the following effects at the AV node.
i. Markedly slows or completely blocks
conduction velocity
ii. Prolongs the refractory period &
iii. Decreases automaticity
•Its MoA is probably by hyperpolarizing the AV node (through increased I K1) and by
reducing calcium current
PK
•Adenosine has an extremely short duration of action (~10 to 15 seconds) due to
rapid uptake by erythrocytes and endothelial cells
Clinical use

•Adenosine is extremely effective in abolishing AV nodal arrhythmia & acute

supraventricular tachycardia.
•Because of its very low toxicity it has become the drug of choice for this arrhythmias.

Adverse effects
•Include transient chest pain and dyspnea (probably due to bronchoconstriction),
flushing, and hypotension
b. Digoxin

•It inhibits the Na+/K+ -ATPase pump

•This leads to:

i. Shortening of the refractory period in atrial and ventricular
myocardial cells &
ii. Prolongation of the effective refractory period and
reduced conduction velocity in the AV node.
Clinical use
•Digoxin is used to control ventricular response rate in atrial fibrillation and flutter;
•However, sympathetic stimulation easily overcomes the inhibitory effects of digoxin.
NB:
•Serum trough concentrations of 1.0 to 2.0 ng/mL are desirable for atrial
fibrillation or flutter, while lower concentrations of 0.5 to 0.8 ng/mL are
targeted for systolic heart failure.
Adverse effects

•At toxic concentrations, digoxin causes ectopic ventricular beats that may result in VT
and fibrillation
c. Magnesium sulfate

MoA
•Magnesium is necessary for the transport of sodium, calcium, and potassium across
cell membranes.
•It slows the rate of SA node impulse formation and prolongs conduction time
along the myocardial tissue.
Clinical use
•IV magnesium sulfate is the salt used to treat arrhythmias
•However, oral magnesium is not effective in the Rx of arrhythmias.

•Magnesium is the drug of choice for treating the potentially fatal arrhythmia torsades
de pointes and digoxin-induced arrhythmias.
d. Potassium Ion

•Potassium depresses ectopic pacemakers, including those caused by digitalis toxicity.

•Hypokalemia is associated with an increased incidence of arrhythmias, especially in
patients receiving digitalis.
•Conversely, excessive potassium levels depress conduction and can cause reentry
arrhythmias.
•There4, when treating arrhythmias, serum K+ should be measured & normalized if
abnormal.