50 S Protein Synthesis Inhibitors Flashcards
Macrolides
large LACTONE ring
Erythromycin Azithromycin Clarithromycin Telithromycin Roxithromycin
Macrolides Coverage
gram (+)
gram (-)
atypical
NO pseudomonas and anaerobic coverage
Treatment of disseminated MAC in AIDS
Clarithromycin
All Macrolides exhibit TIME DEPENDENT KILLING EXCEPT
Azithromycin - concentration dependent
*can cause ARRYTHMIA
Erythromycin stimulates
MOTILIN RELEASE – INC PERISTALSIS – DIARRHEA
Prophylaxis against disseminated MAC in AIDS
Azithromycin
More potent than erythromycin d.t. additional methyl group
Clarithromycin
*has greater activity against H. pylori, M.avium complex, T. gondii
LINCOSAMIDES
Clindamycin
Lincomycin
SULFUR containing antibiotics isolated from Streptomyces lincolnensis
Notorious for causing STEVEN JOHNSON SYNDROME
Lincomycins
Against non-spore forming anaerobic bacteria (Bacteroides fragilis)
CLINDAMYCIN
*AE - pseudomembranous enterocolitis
Coverage of Clindamycin
gram (+)
CA - MRSA
anaerobic organisms
CLINDAMYCIN - anaerobic infections ABOVE the diaphragm except the brain
METRONIDAZOLE - anaerobic infections BELOW the diaphragm including the BRAIN
Causes APLASTIC ANEMIA (bone marrow suppression) and Gray Baby syndrome
Chloramphenicol
Gray color/cyanosis, vomiting, flaccidity, hypothermia, shock
Gray Baby syndrome
LIMIT DOSE (Chloramphenicol) - < 50 mg/kg/d during the 1st week of life
premature neonates - DEFICIENT in hepatic GLUCURONOSYLTRANSFERASE
What metabolic pathway is effective in detoxifying chloramphenicol?
Glucuronidation reaction ( Type of phase 2 reaction)
Established mechanisms of resistance of gram (+) organisms to macrolide antibiotics
Methylase production
Methylation of the receptor site
SE of Macrolides
GI Upset
QT prolongation
Cholestatic hepatitis
ALL macrolides INHIBIT CYP450 EXCEPT
Azithromycin
Macrolide with highest Vd and slowest elimination
Azithromycin
Streptogramins
for drug resistant gram (+) cocci – Staphylococci and E. faecium (MRSA, VRSA, VRE)
Quinupristin-Dalfopristin
SE: arthralgia-myalgia syndrome
Oxalidinone
binds to 23s ribosomal RNA of 50s subunit
for drug resistant gram (+) cocci – Staphylococci and E. faecium (MRSA, VRSA, VRE), Listeria, Corynebacteria
Linezolid
Tedizolid
SE of Chloramphenicol
Gray baby syndrome Aplastic anemia (idiosyncratic)
Chloramphenicol resistance is d.t.
Formation of acetyltransferase that inactivates drug
Characterized by DECREASED RBC, cyanosis and cardiovascular collapse
Gray Baby Syndrome
Premature neonates are deficient in hepatic GLUCORONOSYLTRANSFERASE
Glucuronidation - the way to metabolize chloramphenicol
