pharm macrolides
Terms
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- Macrolides
-
-Erythromycin
prototype
-Clarithromycin
new derivative with improved spectrum and acid stability
-Azithromycin
new derivative with different pharmacokinetics as well as improved spectrum and acid stability - General Spectrum and Clinical Status
-
-Good activity vs. common streptococci plus Bordetella, Chlamydiae , Mycoplasma, Legionella
-Treatment of common respiratory infections (Bordetella, Chlamydiae, Mycoplasma, Legionella)
-Alternative to penicillin in mild-to-moderate infections (esp. common streptococci) -
Chemistry and Mechanism
mech is similar to what other two drugs? -
-large lactone ring (14-15 membered) with aminosugars
-erythromycin base is acid labile
use enteric coating and esters
-new analogs with improved acid stability and spectrum
Clarithromycin and Azithromycin
-bacteriostatic inhibitor of protein synthesis
-cindamycin and chloramphenicol -
Therapeutic Uses
4 -
-Common URTI due to group A strep., Strep. pneumoniae, H. influenzae)
-Otitis media
new analogs useful alone
-Pneumonias due to Mycoplasma, Chlamydiae, and Legionella
-Whooping cough (Bordetella pertussis) - Other Clinical Uses
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--Chronic bronchitis and sinusitis
-Helicobacter pylori in peptic ulcer disease
-Mycobacterium avium complex infections in patients with AIDS
Clarithromycin and Azithromycin -
Spectrum
-Erythromycin
-Clarithromycin
-Azithromycin -
-Streptococci, some H. flu., syphilis, Mycoplasma, Rickettsia, Legionella, Bordetella
-improved to cover mycobacterium avium complex and H. pylori
-similiar to clarithromycin plus increased potency vs. Chlamydiae, H. flu., some gram-neg. bacilli -
Pharmacokinetics
-Absorption (oral)
-Erythromycin
-Clarithromycin
-Azithromycin
- -
-is acid labile (enteric coating or acid resistant esters used)
-taken with food
-taken on empty stomach
-good to most tissues (esp. lung, prostate)
- inadequate to CSF
-Azithromycin best; concentrated in phagocytic cells (macrophages) and fibroblasts -
Excretion
Erythromycin
Azithromycin
Clarithromycin -
-hepatic metabolism (CYP3A)
some biliary secretion
-feces as unchanged drug
prolonged half-life (68 hrs)
given for only 5 days
-unchanged in urine (30%) and feces - Adverse Effects/ Drug Interactions
-
-Erythromycin (Erythrocin)
GI irritation
hepatotoxicity with estolate ester (adults)
inhibits cytochrome P450 (CYP) metabolism
-Clarithromycin (Biaxin)
less GI effects
inhibits CYP metabolism
-Azithromycin (Zithromax)
less GI effects
no inhibition of CYP metabolism - Clinical Problems
-
-Relatively safe drugs
mild GI disturbances
-Bacteriostatic
not used for serious infections susceptible to bactericidal drugs
-Limited distribution
not used for meningitis - New Macrolide Subclass
- ketolide /Telithromycin
- Telithromycin vs Macrolides
-
-Improved activity vs. penicillin- and macrolide-resistant pathogens such as Streptococcus pneumoniae
-Good vs. chlamydiae, Mycoplasma, Bordetella, Legionella
-Variable activity vs. Haemophilus influenzae