Review of Pharmacology - 9E (2015)

Review of Pharmacology
Glycylcyclines
This new group of antibiotics includes tigecycline, which acts by inhibiting protein
synthesis via a mechanism similar to tetracyclines. But these are more resistant than
tetracyclines to efflux pumps developed by the microorganisms. Their main indication is
serious complicated skin and skin structures infections and intra-abdominal infections. It has
a broad spectrum including MRSA, VRSA, streptococci, enterococci, anaerobes, rickettsia,
chlamydia, legionella and rapidly growing mycobacteria. However, it is ineffective against
Proteus and Pseudomonas.
Macrolides
Chemotherapy A: General Considerations and Non-specific...
Clinical uses of Azithromycin
and clarithromycin
C – Chlamydia
H – H.influezae
A – MAC
T – Toxoplasma
Adverse effect of macrolides
M – Motilin receptor agonists
A – Allergy
C – Cholestasis
R Reversible
O Ototoxicity
These antibiotics have large cyclic lactone ring structure with attached sugars. The drugs
included in this group are erythromycin, azithromycin, roxithromycin and clarithromycin. An
immunosuppressant drug, tacrolimus is also a macrolide antibiotic. These drugs bind to
50S ribosome and block the translocation of peptide chain from A to P site. Ketolides and
lincosamides have similar mechanism of action.
Pharmacokinetics
These drugs are well absorbed orally. Erythromycin is excreted by biliary route and
clarithromycin by both renal and biliary routes. Excretion of azithromycin is quite slow
(longest half life) and mainly in the urine. Erythromycin is administered four times a day
whereas azithromycin is administered as a single daily dose.
Clinical Uses
Macrolides are the drug of choice for (remembered as CLAW)
• Chancroid by Haemophilus ducreyi (Azithromycin single dose), Corynebacterium
(diptheria), Campylobacter
• Legionella infections
• Atypical pneumonia
• Whooping cough by Bordetella pertussis
It can also be used for diphtheria and the infections caused by chlamydia and gram positive
organisms (as second choice drugs to penicillins).
• Azithromycin has similar spectrum but is more active against H. influenza and
Neisseria. Because of its long t 1/2
, a single dose is effective in the treatment of urogenital
infections caused by chlamydia. It can be used once weekly in the prophylaxis of
MAC infections.
• Roxithromycin has similar spectrum as that of azithromycin.
• Clarithromycin is approved for the prophylaxis and treatment of Mycobacterium avium
complex and in the treatment of peptic ulcer caused by H. pylori.
• Macrolides have anti-inflammatory action due to their effect on neutrophils and
inflammatory cytokines. This action is responsible for the use of macrolides in the
prevention of cystic fibrosis exacerbation.
• Spiramycin is another macrolide antibiotic that is the drug of choice for the
treatment of toxoplasmosis in pregnancy.
• Fidaxomycin is a non-absorbed macrolide approved for treatment of C. difficile
infection.
Toxicity
• Erythromycin can cause diarrhea by the stimulation of motilin receptors. Gastrointestinal
effects are most common side effects of all macrolides.
• Erythromycin estolate is implicated in the causation of acute cholestatic hepatitis
especially in pregnant females. Other salts of erythromycin are safe.
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