Pharmacology Made Simple : Erythromycin

Join our facebook page for discussions and further good quality learning :
https://www.facebook.com/groups/405813783372378/

Pharmacology Made Simple : Erythromycin

Erythromycin is an antibiotic useful for the treatment of a number of bacterial infections.

This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. 

It may also be used during pregnancy to prevent Group B streptococcal infection in the newborn.

Erythromycin may be used to improve delayed stomach emptying. It can be given intravenously and by mouth.

An eye ointment is routinely recommended after delivery to prevent eye infections in the newborn.

Mechanism of Action :

Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations .It binds to the 50s subunit of the bacterial 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, 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.

Side Effects:

It is generally safe in those who are allergic to penicillin.

Erythromycin also appears to be safe to use during pregnancy.While generally regarded as safe during breastfeeding its use by the mother during the first two weeks of life may increase the risk of pyloric stenosis in the baby.

Common side effects include abdominal cramps, vomiting, and diarrhea. More serious side effects may include Clostridium difficilecolitis, liver problems, prolonged QT, and allergic reactions.

This risk also applies if taken directly by the baby during this age.

It is in the macrolide family and works by decreasing bacterial protein production.

Interactions:

Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular, by isozymes of the CYP3A superfamily, CYP3A.

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 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 and doxycycline can have a synergistic effect when combined and kill bacteria (E. coli) with a higher potency than the sum of the two drugs together.

This synergistic relationship is only temporary. After approximately 72 hours, the relationship shifts to become antagonistic, whereby a 50/50 combination of the two drugs kills less bacteria than if the two drugs were administered separately.