Erythromycin gastrointestinal effects

Colombel, J.F., Cortot, A., Neut, C., and Romond, C., Yogurt with Bifidobacterium longum reduces erythromycin-induced gastrointestinal effects, Lancet, 1, 43, 1987. 

Azithromycin achieves high concentrations in tissues relative to those in plasma. It remains largely unmetabolised and is excreted in the bile and faeces (t) 50h). Azithromycin is used to treat respiratory tract and soft tissue infections, and sexually transmitted diseases, especially genital Chlamydia infections. Gastrointestinal effects (9%) are less than with erythromycin but diarrhoea, nausea and abdominal pain occur. In view of its high hepatic excretion use in patients with liver disease should be avoided. Interactions see erythromycin (above). 

Erythromycin is extensively metabolized, with much of the unchanged parent drug and active metabolite eliminated in bile, resulting in a short half-life (1-3 h). Erythromycin undergoes entero-hepatic recirculation, which may contribute to the adverse gastrointestinal effects seen in adult horses. 

Animals have been reported to develop similar symptoms to those seen in humans when larger doses are used. Horses are particularly sensitive to erythromycin induced gastrointestinal effects. At doses of >5mgkg day, dogs have been reported to develop ventricular arrhythmias. 

Erythromycin is regularly used in veterinary practice and seems to be tolerated well by many animal species. Like humans, animals can develop hypersensitive reactions to erythromycin. Also like humans, acute gastrointestinal effects are the most commonly seen adverse effects. 

Though the clinical need for such measures would be expected to be rare, basic and advanced life-support measures as well as aggressive decontamination should be instituted as clinically necessary. Gastric decontamination may be performed dependent on the symptomatology of the patient and history of the exposure. Activated charcoal will effectively adsorb erythromycin. Gastrointestinal discomfort may be treated symptomatically or by reducing the dosage. 

Although their effectiveness is similar to the tetracyclines, the use of erythromycin and clindamycin is often limited due to their potential adverse outcomes. Erythromycin has treatment failure due to resistance and a high incidence of gastrointestinal intolerance, while clindamycin causes diarrhea and carries a risk of developing pseudomembranous colitis with long-term use.3,8... 

Clarithromycin is a derivative of erythromycin (macrolide). Advantages over erythromycin include lower frequency of gastrointestinal side-effects and lower dosage frequency. Clarithromycin is administered every 12 hours. As with all macrolides it should be used with caution in patients who are at risk of developing QT interval prolongation caused either by electrolyte imbalances or the concomitant use of other drugs. 

Roxithromycin, clarithromycin, azithromycin and dirithromycin are more recently developed macrolides with similar antimicrobial activity to erythromycin. However they are better absorbed, have longer elimination half-lives and lower incidence of gastrointestinal side-effects. Azithromycin and... 

The incidence of side effects associated with erythromycin therapy is very low. Mild gastrointestinal upset with nausea, diarrhea, and abdominal pain are reported to occur more commonly when the propionate and es-tolate salts are used. Rashes are seen infrequently but may be a part of a general hypersensitivity reaction that includes fever and eosinophilia. Thrombophlebitis may follow intravenous administration, as may transient impairment of hearing. 

Several antibiotics have been used to treat intestinal protozoal infections. Erythromycin and tetracycline do not have a direct effect on the protozoa they act by altering intestinal bacterial flora and preventing secondary infection. Tetracycline also reduces the normal gastrointestinal bacterial flora on which the amebas depend for growth. 

Pharmacokinetics attd Pharmacology. Older macrolides such as erythromycin exhibit relatively low serum concentrations, short in vivo half-hves, highly variable oral absorption, and low oral bioavailability. Improvements in these pharmacokinetic parameters have been accomplished for newer derivatives. The principal side effects of macrolides aie gastrointestinal problems, such as pain, indigestion, diarrhea, nausea, and vomiting. 

Epigastric distress This side effect is common and can lead to poor patient compliance for erythromycin. The new macrolides seem to be better tolerated by the patient gastrointestinal problems are their most common side effects. 

Tetracyclines are recommended as first-line treatment. When tetracyclines are not tolerated or contraindicated, erythromycin is an alternative. However erythromycin has problems with resistance and gastrointestinal adverse effects. If compliance is a problem, either doxycycline or lymecycline may be prescribed (can be taken once daily with food). Minocycline is second-line treatment (e.g. if oral antibiotic has failed). 

Although erythromycin is also effective in treating irritable bowel syndrome, its use is limited because of gastrointestinal side effects. 

Gastrointestinal irritation, including abdominal cramps, nausea, vomiting, and diarrhea, is the most common adverse event produced by erythromycin and is usually associated with oral administration. Irritation is dose related and more common with daily doses of 2 g or more. Some brands of enteric-coated tablets and the ester derivatives (e.g., ethylsuccinate) can be taken with food to minimize these adverse effects. 

Like erythromycin, the most common side effects of azithromycin and clarithromycin are gastrointestinal, with diarrhea, nausea, and abdominal pain being the most frequently reported. Clarithromycin can also cause headache and dyspepsia. Other side effects of azithromycin include palpitations, vaginitis, headache, dizziness, fatigue, and hypersensitivity reactions. 

Gastrointestinal symptoms were the most common adverse effects reported in a trial of azithromycin in disseminated Mycobacterium avium complex in 62 patients with AIDS (30). Erythromycin is a motilin receptor agonist (31-33). This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides. Azithromycin may act on gastrointestinal motility in a similar way to erythromycin, as it produces a significant increase in postprandial antral motility (34). 

Acute hemorrhagic colitis without pseudomembranes has been reported after oral cefuroxime (SEDA 21, 261). In mice, some cephalosporins accelerated gastric emptying, in some instances even more effectively than erythromycin or metoclopramide (93). The relevance of this to the gastrointestinal adverse effects of cephalosporins, such as nausea and vomiting, is uncertain. 

The gastrointestinal adverse effects are the most common untoward effects of the macrolides (Table 2). Nausea and vomiting associated with abdominal pain and occasionally diarrhea can be minor and transitory or, in a small percentage of patients, become severe enough to result in premature withdrawal. The rate of these adverse effects varies among the different antibiotics. In general, newer macrolides, such as azithromycin, clarithromycin, or roxithromycin, are better tolerated and cause fewer adverse effects than erythromycin. 

Erythromycin is a motUrn receptor agonist (2-4). This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides. 

The macrolide antibiotics include erythromycin, clarithromycin, azithromycin, tylosin, tilmicosin and tiamulin. Clindamycin and lincomycin are related lincosamides. Susceptible bacteria include staphylococci, streptococci, Campylobacter jejunii, Clostridium spp., R. equi, Mycoplasma pneumoniae and Chlamydia spp. Drugs in this group are only effective against a few Gram-negative bacteria in cattle, namely some strains of Pasteurella and Haemophilus spp. Macrolides and lincosamides are associated with causing colitis in horses, so their use is usually restricted to p.o. erythromycin for the treatment of R. equi infections in foals. Subantimicrobial doses of erythromycin are administered i.v. to horses for gastrointestinal prokinetic action. 

The gastrointestinal tract is a frequent site for adverse effects of antimicrobial drugs, primarily because of disruption of normal intestinal microbial populations and proliferation of enteropatho-gens. Diarrhea, often with accompanying signs of endotoxemia, is the usual clinical manifestation. Antimicrobial agents known to be, or implicated in being, associated with antimicrobial-induced diarrhea include penicillin, ceftiofur, lincomycin, tetracycline, erythromycin and the potentiated sulfonamides. Erythromycin can also promote diarrhea via its motilide activity. 

Patients presenting with acute erythromycin overdose are usually asymptomatic or experiencing minor to moderate gastrointestinal side effects/ discomfort. Serious cardiac effects, including prolongation of the QT interval, arrhythmias (i.e., ventricular tachycardia. Torsades de Pointes, ventricular fibrillation, and heart block), may be observed after rapid intravenous administration and coincident with high, peak erythromycin plasma concentrations. The occurrences of these QT prolongation-associated arrhythmias are rare. 

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