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Arrhythmias consist of cardiac depolarizations that deviate from the above description in one

or more aspects: there is an abnormality in the site of origin of the impulse, its rate or

regularity, or its conduction.

The macrolide antibiotics, also interact with the commonly prescribed anticoagulant warfarin,

which, among other drugs is metabolized by the CYP!" system with predominant

involvment of CYP#A.,$ As the therapeutic range of warfarin is narrow, warfarin treatment

needs to be monitored carefully with dose reduction when concomitant treatment with

macrolides is instituted.

Ten percent of population on chronic digo%in therapy convert upto "& of ingested digo%in

to inactive digo%in reduction products '()Ps* due to action of +ubacterium lentum, an

anaerobic bacillus which is part of normal gut flora. t has been suggested that macrolide

antibiotics, especially erythromycin and possibly clarithomycin alter the gut flora by

decreasing +ubacterium -entum in the gut, thereby reducing the conversion of digo%in to

()Ps$/ and thus increasing serum digo%in level leading to to%ic effects and increased

morbidity.

Another possible mechanism of clarithromycin and digo%in interaction is reduction of renal

e%cretion of digo%in. t is suggested that Pglycoprotein plays an important role in the renal

secretion of digo%in, and that clarithromycin can decrease renal digo%in e%cretion by

inhibiting Pglycoproteinmediated transport.

Almost all antibiotics can potentiate the effects of warfarin by inhibiting its hepatic

metabolism. +rythromycinwarfarin interaction has shown that erythromycin can mar0edly

elevate the prothrombin time by inhibition of CYP!" system. +rythromycin and

troleandomycin have the highest affinity for CYP#A isoenzyme and therefore the strongest

ability to inhibit substrate brea0down. Clarithromycin has a lower affinity for cytochrome

system, leading to less significant interactions with substrates of CYP#A. 1ince

clarithromycin potentiates the effect of warfarin, careful monitoring of 2) is warranted.

The primary mechanisms by which antibiotic medications interact with warfarin to increase

the ris0 of ma3or bleeding is through disruption of intestinal flora that synthesize vitamin

4, and inhibition of cytochrome p!" isozymes which metabolize warfarin.

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5e found that the e%posure to any antibiotic agent was associated with a twofold increased

ris0 of bleeding that re6uired hospitalization among older continuous warfarin users. All si%

specific antibiotic drug classes e%amined 'azole antifungals, macrolides, 6uinolones,

cotrimo%azole, penicillins, and cephalosporins* were associated with an increased ris0 of

bleeding. 7ur finding that patients who were prescribed azole antifungals and cotrimo%azole

had the highest ris0s of hospitalization for bleeding is consistent with previous studies.

Cardiac glycosides have been used since the eighteenth century as a remedy for heart failure,

a pathological condition in which the heart is unable to contract forcefully. These highly to%ic

drugs depress 2a848ATPase activity in all cells, not 3ust those of the heart. 5ith depressed

2a848ATPase activity, 2a8 builds up in the cytosol, and the concentration gradient for 2a8

across the cell membrane diminishes. This in turn decreases the potential energy available for

indirect active transport. n the myocardial cell, cardiac glycosides decrease the cell s ability

to remove Ca98 by means of the 2a8Ca98 e%changer. The resultant increase in cytosolic

Ca98 causes more forceful myocardial contractions.

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