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Dr S A Jayaratne
Dept of Pharmacology
Inotropes
Cardiac glycosides (steroid inotropes)
Was first discovered by Sir William Withering
Crude digitalis is the extract of dried leaf of the
foxglove plant (Digitalis purpurea)
Digitalis has several active glycosides which include
digoxin & lanatosides
Digoxin is the most important therapeutically
Mechanism of action
Direct
Indirect
Mechanism of action-direct
Inhibits membrane bound enzyme sodium-potassium
adenosine triphosphatase (Na+/K+ATPase). This
enzyme supply energy for the system that pumps Na+
+ out & K+into contracting& conducting tissues
Mechanism of action-indirect
Enhances vagal activity via an action on the
central nervous system and diminishes
sympathetic activity
Digoxin- Pharmacokinetics
Administered orally variable absorption (iv
infusion rarely)
Plasma half life of 36-48 hours
(normal renal function prolonged in renal
failure & elderly)
Maintenance dose administered once daily
85% is eliminated unchanged by the kidney
15% is metabolised by the liver
Clinical indications
1) Treatment of heart failure
increase contractility
Is useful in heart failure associated with sinus
rhythm
Also useful in heart failure associated with
atrial fibrillation
Adverse effects
Adverse effects related to
Plasma concentration
Sensitivity of myocardium & conducting
system to digoxin
Digoxin Toxicity
Potential for development of toxic effects is
increased in In renal failure dose should be reduced
Elderly
Hypothyroidism-intolerant of digoxin
Hypokalaemia
Hypomagnesaemia
(cardiac stimulants)
Sympathomimetics: Beta-1 adrenoceptor
stimulants such as dobutamine and dopamine
since they increase cardiac contractility and
cause some vasodilation.
Mechanism of action
Acts on 1 adrenoceptor in the myocardium
increases myocardial contractility and heart
rate
Activation of adrenoceptors
results in vasoconstriction
Clinical uses
Used in the treatment of Cardiogenic shock
post myocardial infarction or
following cardiac surgery
Phosphodiesterase inhibitors
These drugs cause an increase in cylic AMP by
inhibiting cardiac phosphodiesterase.
The increase in cAMP results in an increase in
transmembrane calcium flux
a secondary increase in cardiac contractility.
Amrinone, milrinone -withdrawn in certain
countries
Not used in Sri-lanka