Cardiac glycosides,

antiarrhythemic drugs
Dr.Jibachha Sah
M.V.Sc (Pharmacology)
College of veterinary Science,NPI,
Bhojard,Chitwan
Introduction

Cardiac glycosides are a class of organic compounds that increase the output force of the
heart and increase its rate of contractions by acting on the cellular sodium-potassium
ATPase pump

Their beneficial medical uses are as treatments for congestive heart failure and cardiac
arrhythmias.
Mechanism of action of cardiac glycosides

Cellular mechanism of action of cardiac glycosides. It has long been known that cardiac
glycosides can inhibit the membrane sodium-potassium (Na+-K+) pump, raising intracellular
Na+.

Digitalis and its derivatives such as digoxin and digitoxin are cardiac glycosides used typically
in the therapy of congestive heart failure and atrial fibrillation.

Cardiac glycosides are found in a diverse group of plants including Digitalis purpurea and
Digitalis lanata (foxgloves), Nerium oleander ...
Biochemical Mechanism of Action

The mechanism whereby cardiac glycosides cause a positive inotropic effect and
electrophysiologic changes is still not completely clear. Several mechanisms have been
proposed, but the most widely accepted involves the ability of cardiac glycosides to inhibit
the membrane bound Na+-K+-ATPase pump responsible for Na+-K+ exchange.
The process of muscle contraction can be pictured as shown below.
The process of membrane depolarization / repolarization is controlled by the
movement of three cations, Na+, Ca+2, and K+, in and out of the cell.

the resting stage, the concentration of Na+ is high on the outside. On membrane
depolarization sodium fluxes-in leading to an immediate elevation of the action
potential. Elevated intracellular Na+ triggers the influx of free of Ca++ that occurs
more slowly.

The higher intracellular [Ca++] results in the efflux of K+. The reestablishment of the
action potential occurs later by the reverse of the Na+-K+ exchange.

The Na+ / K+ exchange requires energy which is provided by an enzyme Na+-K+-ATPase.

Cardiac glycosides are proposed to inhibit this enzyme with a net result of reduced
sodium exchange with potassium that leaves increased intracellular Na+. This results in
increased intracellular [Ca++].

Elevated intracellular calcium concentration triggers a series of intracellular biochemical

events that ultimately result in an increase in the force of the myocardial contraction or a
positive inotropic effect.
Antiarrhythemic drugs
Class Drug group •Main mechanism •Examples
of action

Class I •Fast sodium •Inhibit •Moderate Quinidine

antiarrhythmic channel blockers conduction blockade of Na+ Procainamide
drugs velocity(negative channels(interme Disopyramide
dromotropy), part diate Ajmalin
icularly in
depolarized
tissue (e.g.,
during tachycardia
)

Class IB antiarrhythmics •Weak blockade of Na+ •Lidocaine

channels (fast •Mexiletin
association/dissociation)
•Shorten AP duration (left
shift) → slow ERP
•Strongest effect
on ischemic myocardium
 Class IC antiarrhythmics •Strong blockade of Na+ •Flecainide
channels (slow •Propafenone
association/dissociation) →
QRS prolongation
•No to minimal effect on
AP duration (no
shift) → ERP unaffected

Class II •Beta blocker •Inhibit β- •Metoprolol

antiarrhythmic drugs adrenergic activation •Esmolol
of adenylate cyclase •Propranolol
→↓ cAMP → ↓ •Atenolol
2+
Ca •Timolol
•Decrease slope of •Carvedilol
phase 4 in •Sotalo
pacemaker cells,
leading to a slower
conduction velocity
 Class III •Potassium •Inhibit •Amiodarone
antiarrhythmic drugs channel blocker potassium delayed r •Dronedarone
ectifier currents •Sotalol
•Prolongs AP •Bretylium
duration (Reverse •Ibutilide
use-dependence) •Dofetilide
and effective
refractory
period (ERP)
•No effect on
conduction velocity

lass IV •Calcium channel •Inhibit slow calcium •Verapamil

antiarrhythmic drugs blocker channels •Diltiazem
•Decrease slope of •Nifedipine
phase 0 and 4 →
slower conduction
velocity
•Prolong repolarization
of AV node
•Decreasing
conduction velocity
leads to
 Class V •Variable •See section on •Adenosine
antiarrhythmic drugs mechanisms “Other •Digoxin
antiarrhythmic •Magnesium
drugs” below for sulfate
details.