myocardium
Stimuation of the
Digoxin:
myiocardial contractility (+inotropic effect) mostly in dilating failing
improve the
heart in longer term, once the episode of H.F. has been brought under control.
This effect occurs in patients in sinus rhythm as it is separated from its (-ev inotropic
effect) action of reducing ventricular rate & thus improving ventricular rate in
Fibrillation .
Digoxin is belong to groups of drugs derived from plants called (fox glove) which
contain digoxin, digitoxin, quabine straphanthen, these are extracts of the above
plants called cardiac glycosides which are used in treatment of HF.
Mechanism of action:=
1-Direct effect
In each cardiac cells there is Na+, k+and ATPase system (pump), this act to push Na+
outside the cell in exchange to K+ when goes inside the cells. In addition there is
Na+, Ca++ exchange, when Na+ goes inside the cells , the Ca++ goes outside the cells
(this is not depend on ATPase system).
If we inhibit NA+, k+, ATPase system, so the Na+ will accumulate inside the cell and
increase its concentrations, and the increase of this concentration causing less inters
of Na+ from outside and this will led to less Ca++ outside the cell and the end result
is increase of Ca++inside the cell so this increase the force of the contraction.
2-Digoxin inhibit Na+, K+, ATPase system.
Digoxin act opposite action to K+ , so hypokalemia can aggravate digoxin toxicity.
3-Ca++ act in similar to the way of digoxin, other mechanism of cardiac glycosides
can facilitate the entrance of Ca++into the cell through the Ca++channel and also can
increase the release of Ca++ from the storage site inside the cell.
**Indirect Effects:-
1-It delay or slow the conduction mainly through the AV node, and this
important in treatment of aterial fibrillation .
2-DIGOXIN is contra-indicated in WPW Syndrome .
3- DIGOXIN is enhance vagal activity (cholenomymetic activity) in which
DIGOXIN can cause bradycardia.
4- DIGOXIN can effect the membrane potential in action potential .
(A hours is tired and fold on it)
5-On ECG DIGOXIN cause flatting of T-wave and depression of ST-segment
due to reduction of membrane potential, Prolong the P-R interval and
shorting of QT interval because of the effects of the repolarization.
PHARMACOKINITIC
Absorb well from GIT . 25% to the plasma protein ie low protein binding , 50%
excreted unchanged in the urine and has narrow therapeutic index, so we
give the patients the digeltizing doses or loading doses as follow:-
start)
2mg/ml (at
-
day 0.5
st
1 x 3 1
day after 5 t1/2 (t1/2 =36hr)
nd
1 x 2 2
SIDE EFFECT
1-Nausia , vomiting due to irritation to GIT mucosa as well as central effects.
2-All types of arrhythmias.
3-it can cause heart block
4-Gynaecomastia bec it contain steroid ring and interfere with sex.
5-CNS like headache , dizziness and interfere with vision and color that it
inhibit Na+, K+. ATPase system in retina so causing haloes.
6-Skin rash.
DIGOXIN TOXICITY
This depend on the dose
1-It should adjust the doses , we should measure the serum K+ IN DIGOXIN
toxicity.
-
I anti
) is specific for digoxin arrhythmias bec it is class
Epanutin
Phenytoin (
-
2
arrhythmic drug and bec it facilitate the conduction through the AV-node .
3-Atropin used for bradycardia due to digoxin toxicity.
4-*Digoxin specific antibody which is prepared by the way of radio-immuno-
assy.
This is called degibind which is antbody to digoxin and given by the way of IV
rout.
