Chemical structure of erythromycin.
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Eryped

Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea. Structurally, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desoamine), making it a compound very difficult to produce via synthetic methods. more...

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Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

History

Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate Erythromycin from the metabolic products of a strain of Streptomyces erythreus found in the samples. The product was subsequently launched in 1952 under the brand name Ilosone® (after the Philippine region of Iloilo where it was originally collected from). Erythromycin was formerly also called Ilotycin®. In 1981, Nobel laurate (1965 in chemistry) and Professor of Chemistry at Harvard University (Cambridge, MA) Robert B. Woodward and a large team of researchers reported the first stereocontrolled asymmetric chemical synthesis of Erythromycin A.

Available forms

Erythromycin is available in enteric-coated tablets, oral suspensions, opthalmic solutions, ointments, gels and injections.

Mechanism of action

Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translation of peptides.

Pharmacokinetics

Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused 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.

Metabolism

Most of erythromycin is metabolised by demethylation in the liver. Its main elimination route is in the bile, and a small portion in the urine. Erythromycin's half-life is 1.5 hours.

Side-effects

Gastrointestinal intestinal disturbances such as diarrhea, nausea, abdominal pain and vomiting are fairly common so it tends not to be prescribed as a first-line drug. More serious side-effects, such as reversible deafness are rare. Allergic reactions, while uncommon, may occur, ranging from urticaria to anaphylaxis. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrolysis are some other rare side effects that may occur.

Erythromycin has been shown to increase the probability of pyloric stenosis in children whose mothers took the drug during the late stages of pregnancy or while nursing.

Contraindications

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 (Ray et al 2004). Hence, erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap).

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How to take your medication: erythromycin
From FDA Consumer, 4/1/91 by Paula Kurtzweil

How you take a drug can affect how well it works and how safe it will be for you. Sometimes it can be almost as important as what you take. Timing, what you eat and when you eat, proper dose, and many other factors can mean the difference between feeling better, staying the same, or even feeling worse. This drug information page is intended to help you make your treatment work as effectively as possible. It is important to note, however, that this is only a guideline. You should talk to your doctor about how and when to take any prescribed drugs.

The ninth installment in this series of articles on commonly prescribed medications is about erythromycin, an antibiotic used alone or in combination with other chemicals or drugs to treat various infections. Erythromycins also are used as part of a preoperative bowel preparation that suppresses the normal bacterial flora, thus reducing the chances of infection following bowel surgery.

Conditions These Drugs Treat

Erythromycin was first isolated in 1952. Like other antibiotics, it is produced by a microorganism-in this case, Streptomyces erythraeus-and has the capacity to inhibit the growth of or to kill other microorganisms. It is effective against a number of common bacteria, including Chlamydia trachomatis, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Listeria monocytogenes, Streptococcus pneumoniae, Bordetella pertussis, Legionella pneumophilia, and Mycoplasma pneumoniae.

It is used to treat conditions caused by those organisms, such as diphtheria, gonorrhea, Legionnaires' disease, pneumonia, sinusitis caused by S. pneumoniae, pertussis (whooping cough), rheumatic fever, and chlamydial infections of the eyes and genitourinary tract and, in infants, lungs. It also is used for penicillin-allergic patients who have syphilis.

The skin preparations are prescribed for acne.

Erythromycin will not cure or combat colds, flu, or other viral infections.

How to Take

Erythromycin may be applied to the eyes (eye ointment) or to the skin (topical gels, ointments, swabs or liquids), swallowed (liquid, tablet or capsule), or administered intravenously fluid).

The doctor determines the dosage, including the dose and treatment period, depending on the type and severity of the infection.

The medication should be taken for the full time prescribed, even if symptoms are no longer present, to ensure that the infection does not recur. The exception might be if side effects occur, in which case the doctor should be consulted. For patients with "strep" infection, it is important that the medicine be taken for at least 10 days, or as prescribed by the doctor. Serious heart problems, such as rheumatic fever, could develop later if the infection isn't cleared up completely.

In general, the eye ointment is applied at least twice daily, the skin preparations twice daily (in the morning and at night), and erythromycin taken by mouth is taken daily at 6- or 12-hour intervals. Intravenous erythromycin is given continuously. mycin

Most oral forms of erythromycin are absorbed best on an empty stomach and therefore should be taken at least one-half hour before or two hours after a meal. They may be taken with food, however, if they upset the stomach.

Of special note: Chewable tablets, such as Ilosone and EryPed chewable tablets, must be chewed or crushed before they are swallowed.

Delayed-release capsules or tablets, such as Ery-Tab and E-Base delayed-release tablets, should be swallowed whole; they should not be broken or crushed.

Specially marked spoons or other measuring devices that come with liquid oral forms should be used to ensure accurate doses. Household teaspoons should not be used because they may not hold the right amount of liquid.

Missed Doses

Erythromycin taken by mouth works best if it circulates in the blood at a constant level. Therefore, it is important that doses not be missed and that they be taken at regular intervals.

If a dose is missed and just a short time has passed, it should be taken as soon as possible. However, if it is time for the next dose, a physician should be consulted before making up the dose.

Relief of Symptoms

Erythromycin usually clears infections within days. However, because it does not relieve symptoms immediately, the doctor may prescribe other medicines, such as aspirin or acetaminophen, to ease pain and fever until the erythromycin takes effect.

Side Effects and Risks

Erythromycin taken by mouth may cause mild stomach cramps, diarrhea, nausea and vomiting, and sore mouth or tongue. These problems are usually minor and may go away as the body adjusts to the medicine. If they persist, however, the doctor should be consulted.

Although relatively rare, other side effects that may occur are:

* with eye ointment: eye irritation not present before therapy

* with skin preparations: dry or scaly skin; itching, stinging, peeling, or redness of the skin

* with medications taken by mouth: skin rash, hives, or itching; dark or amber urine; pale stools; severe stomach pain; unusual tiredness or weakness; or yellow eyes or skin (jaundice)

With intravenous administration: pain, swelling or redness at the injection site.

The doctor should be consulted if any of these side effects occurs.

Precautions and Warnings

Because various adverse drug interactions between erythromycin and other medications can occur, patients should inform their doctors of all prescription and nonprescription drugs they are taking before starting this medicine.

Patients also should tell their doctors:

* if they have ever had an unusual reaction to erythromycin

* if they are pregnant or could possibly become pregnant. Although erythromycin has not been shown to cause birth defects or other problems in humans, it does cross the placenta.

* if they are breast-feeding. Because erythromycin passes into breast milk, a nursing mother should consult her doctor before taking the drug.

* if they are on a low-sodium, low-sugar, or other special diet, or if they are allergic to any foods, sulfites, or other preservatives or dyes that also may be present in an erythromycin-based drug.

* if they have ever had liver disease or hearing loss. Although very rare, patients with kidney problems who take erythromycin may suffer hearing loss, which is reversible after the drug is stopped.

COPYRIGHT 1991 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

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