Flashcards in Macrolides, clindamycin, and chloramphenicol Lecture 19 Deck (20):
Structure and chemistry of erythromycin, clarithromycin, and azithromycin
clarithromycin is a 6 methoxy erythromycin
azithrymycin has a nitrogen group added to the 14 member macrolide ring
MoA of erythromycin, clarithromycin, and azithromycin
reversibly binds to the 50s ribosomal subunit of bacteria to decrease protein synthesis
absorption of erythromycin, clarithromycin, and azithromycin
Erythromycin: base, stearate, and ethylsuccinate are more completly absorbed in the fasting state. Erythromycin estolate is not affected by food.
Distribution erythromycin, clarithromycin, and azithromycin
distributes in tissues longer than in blood
hgh concentrations in alveolar macrophages and leukocytes compared to those in extracellular fluid
azithromycin tissue concentrations exceeds serub by 10-100 fold: allows for 5 day course of therapy
Metabolism/excretion erythromycin, clarithromycin, and azithromycin
erythromycin/clarithromycin: hepatic metabolism. 1.4 h half life
clarithromycin: metabolized in the liver by oxidation and hydrolysis. 20-30% of drug excreted into the urine unchanged.
azithrymycin: major route of elimination in feces via biliary excretion. 68 hr half life, consistent witha slow release of drug from tissues. Aids in allowing 5 day regimen
Erythromycin: Gi abdominal crambs, N/V/D, stimulates the motolin receptor in the gut and hormone that stimulates gastric motility.
Cholestatic hepatitis (rare) Estolate prep; chiefly in adults and pregnant paitnets (avoid estolate form in pregnancy).
N/V, abdominal pain followed by jaundice, fever, LFT changes, Hypsersensitivity reaction to the structure of the estolate compound
generally clears up within days to a few weeks of d/c
AE: clarithromycin, and azithromycin
Gi- not as severe as erythromycin
Drug interactions erythromycin, clarithromycin, and azithromycin
erythromycin/clarithromycin: Erythromycin: generally by interfering with cytochorme p450 enzymes. Metabolites form inactive complexes with p450. Decreased matbaolism of theophylline, warfarin, carbamazepine, cyclosporine
azithrymycin: does not inactivate p450
SoA: erythromycin, clarithromycin, and azithromycin
G+, Atypicals (all three)
H. Flu, M.Cat (clarithro, azithro)
clarithro: h pylori
uses: erythromycin, clarithromycin, and azithromycin
penicillin allergic patients
chlamydia trachomatis nongonococcal urethrtisis and cervicities: single i gm dose of azithromycin= 7 days of doxycycline
C. trachomatis during pregnancy (but not the estolate form)
derived from lincymycin
chemical modification allowed clindamycin more potency and absorption
Binding of 50 S ribosome resulting in inhibition of protein synthesis
Bioavailability= 90%; food delays absorption but does not affect extent
good tissue penetration
metabolized by the liver
G+ and anaerobic coverage.
Strep, Staph (limited bactericidal rate compared to b lactams), anaerobes: bacteroids, including B fragilis, clostridium perfringens, peptostreptococci, peptococci, toxoplasmosis (allergic to sulfonamides)
diarrhea: 20% of patients; more common with oral form
clostridium difficile (pseudomembranous colitis)- big culprit
hepatotoxicitiy (mild to severe)
reversibly binds to the larger 50 S subunit of the 70 S ribosome
suspension: must be hydrolyzed in the intestines for active chloramphenicol
IV form has incomplete hydrolysis; therefore, serum concentrations after IV therapy are only about 70% of those after oral administration
excellent CSF concentrations, 30-50% without inflamed meninges
metabolism via glucuronidation in the liver
wide variations in metabolism and excretion in children: must monitor serum levels
wide variety of G+, G-, aerobic and anaerobic organisms.
Hematologic: reversible bone marrow depression due to direct pharacologic effect on inhibition of mitochondrial protein synthesis. Anemia, leukopenia, thrombocytopenia.
Idiosyncratic aplastic anemia: majority of cases occur weeks to months after completion of therapy and is not necessairly dose related
childhood leukemia: increased incidence
Gray baby syndrome: abdominal distention, vomiting, cyanosis, circulatory collapse. DIminished ability of neonates to conjugate chloramphenicol and to excrete the active form in the urine. Generally associated with concentrations > 50mcg/ml