Side Effects Toxicity and Contraindications of the Macrolide Antibiotics

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The majority of side effects associated with macrolide antibiotics are mild and transient in nature. The most frequently reported events in adults are diarrhea, nausea, abnormal taste, dyspepsia, abdominal pain (substantially less with newer macrolides), and headache. Like other kinds of antibiotics, pseudomembranous colitis has been reported with macrolide use, ranging in severity from mild to life-threatening. There have been isolated reports of transient central nervous system side effects such as confusion, hallucinations, seizures, and vertigo associated with erythromycin use.

Macrolides are known to interact with cy-tochrome P450-dependent monooxygenases that affect the metabolism and elimination of

other drugs (131). Thus, macrolides may have an impact on the drug level of other drugs using these enzymes for drug metabolism. For example, combined therapy with a macrolide and theophylline (a bronchodilator) or car-bamazepine (a psychotropic drug) causes an increase in the serum levels of the latter drugs. Cardiac arrhythmias such as ventricular tachycardia have been reported in patients receivingerythromycin A therapy. Thus, mac-rolides are contraindicated in patients receiving terfenadine therapy who have preexisting cardiac abnormalities (arrhythmia, bradycar-dia, QT interval prolongation, ischemic heart disease and congestive heart failure). Hepato-toxicity (132), ototoxicity (133), dermatologie effects (134), pancreatitis (135), cardiovascular toxicity such as QT prolongation (136) and induced hypotension (137), and hemolytic anemia (138) have been reported less commonly for some earlier macrolides.

4.3 Pharmacology and Mode of Action of the Macrolide Antibiotics

Macrolide antibiotics are primarily administered orally. They are readily absorbed from the gastrointestinal tract (139, 140). Because macrolides are weakly basic, they are predominantly absorbed in the alkaline intestinal environment. Erythromycin A is acid unstable. Thus, its absorption among different patients is highly variable. The drug degrades differently during its passage through the acid environment of the stomach of different patients. The lower bioavailability of earlier macrolides is the result of acidic instability, incomplete absorption, and a first-pass effect. Many different water-insoluble salts or esters

I R = H;II R = acetyl;III R = propionyl

4 Macrolide Antibiotics

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