What is/are Erythromycin?
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often prescribed for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including Mycoplasma and legionellosis. It was first marketed by Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester prodrug that is commonly administered). It is also occasionally used as a prokinetic agent.
In structure, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desosamine), making it a compound very difficult to produce via synthetic methods.
Erythromycin is produced from a strain of the actinomycete Saccharopolyspora erythraea.
Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very common because erythromycin is a motilin agonist. Because of this, erythromycin tends not to be prescribed as a first-line drug. However, erythromycin may be useful in treating gastroparesis due to this pro-motility effect. Intravenous erythromycin may also be used in endoscopy as an adjunct to clear gastric contents.
More serious side-effects include arrhythmia with prolonged QTc intervals including Torsades de pointes and reversible deafness. Allergic reactions range from urticaria to anaphylaxis. Cholestasis, Stevens–Johnson syndrome, and toxic epidermal necrolysis are some other rare side-effects that may occur.
Exposure to erythromycin (especially long courses at antimicrobial doses, and also through breastfeeding) has been linked to an increased probability of pyloric stenosis in young infants. Erythromycin used for feeding intolerance in young infants has not been associated with hypertrophic pyloric stenosis.
Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant women in the form of elevated serum glutamic-oxaloacetic transaminase and is not recommended during pregnancy. Some evidence suggests similar hepatotoxicity in other populations.
It can also affect the central nervous system, causing psychotic reactions, nightmares and night sweats.
It may also alter the effectiveness of combined oral contraceptive pills because of its effect on the gut flora. Erythromycin is an inhibitor of the cytochrome P450 system, which means that it can have a rapid effect on levels of other drugs metabolised by this system, e.g., warfarin.
Mechanism of action
Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations, but the mechanism is not fully understood. By binding to the 50s subunit of the bacterial 70s rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited. Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Without this translocation, the A site remains occupied and, thus, the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action.
Erythromycin is easily inactivated by gastric acid; therefore, all orally-administered formulations are given as either enteric-coated or more-stable salts or esters, such as erythromycin ethylsuccinate. Erythromycin is very rapidly absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where, during active phagocytosis, large concentrations of erythromycin are released.
Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular, by isozymes of the CYP3A superfamily, CYP3A (Hunt et al., 1992). The activity of the CYP3A enzymes can be induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates — drugs that are broken down by CYP3A - such as simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor)—are taken concomitantly with erythromycin, levels of the substrates will increase, often causing adverse effects. A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Another group of CYP3A4 substrates are drugs used for migraine such as ergotamine and dihydroergotamine; their adverse effects may be more pronounced if erythromycin is associated. Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4. Hence, erythromycin should not be administered to people using these drugs, or drugs that also prolong the QT interval. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Theophylline, which is used mostly in asthma, is also contraindicated.
Erythromycin is not recommended when using clindamycin-containing products, even topical products such as Duac or BenzaClin. In general, the simultaneous use of two different erythromycin derivatives (such as clindamycin and Mitemcinal) should be avoided as drugs in this macrolide family possess a common mechanism of action.
This article uses material from the Wikipedia article Erythromycin, which is released under the Creative Commons Attribution-Share-Alike License 3.0.