Macrolides, Clindamycin, Chloramphenicol Flashcards
What is the MoA of macrolides?
Reversible binds to the 50S-ribosomal subunit of bacteria, decreasing protein synthesis
Bacteriostatic
What are the mechanisms of resistance to macrolides?
Decreased permeability of the cell envelope
Alteration in 50S ribosomal receptor site
Enzymatic inactivation of erythromycin by esterases
Describe the absorption of erythromycin.
Erythromycin base is rapidly inactivated by gastric acid
Absorbed better in fasting state
Emycin estolate - not affected by food
Describe the distribution of macrolides..
Distributes in tissues longer than in blood
Very high concentrations in alveolar macrophages and leukocytes
What is significant about azithromycin tissue concentrations.
10-100x serum concentrations
Allows for 5 day course of therapy
How is erythromycin metabolized/excreted?
Inactivated in the liver by demethylation
Biliary excretion mostly, small percentage in urine
What is clarithromycin metabolized/excreted?
Metabolized in the liver by oxidation and hydrolysis
20-30% of drug excreted into urine unchanged
How is azithromycin metabolized/excreted?
Small proportion is metabolized
Biliary excretion
T1/2 = 68hrs - slow release from tissue, 5 day regimen
What are the ADRs of erythromycin?
GI - abdominal cramps
Thrombphelbitis
Cholestatic hepatitis (avoid estolate in pregnancy)
Large IV doses - ototocicity, QT prolongation
What are the ADRs of clarithromycin/azithromycin?
GI - less severe than erythromycin
HA
Dizziness
Allergic reaction
What are the drug interactions for erythromycin/clarithromycin?
Inactivates p450
Decreased metabolism: Theophylline, Warfarin, Carbamazepine, cyclosporine
*azithromycin doesn’t affect p450
What is the spectrum of activity for erythromycin?
G+ (staph and strep)
Atypicals
What is the spectrum of activity of Clarithromycin/Azithromycin?
H. flu, M. Cat** (difference from erythro.)
MAC
What is a prevpak?
Treatment for H. pylori
Amoxicillin 1gm BID, PPI BID, Clarithromycin 500mg BID
What are the indications for the macrolides?
Penicillin allergy
CAP (clar. and azith.)
M. pneumoniae
Legionnaire’s disease
Chlamydia trachomatis
What is the structure and MoA of clindamycin?
Derived from lincomycin, but more potent
Binding of 50S ribosome, inhibiting protein synthesis
What is the bioavailability and metabolization of clindamycin?
Bio. - 90%, food delays absorption
Metabolized by liver
What is the spectrum of activity for clindamycin?
Strep/Staph
Anaerobes (Bacteroides, Clostridium, Peptostrep. peptococcus)
Toxoplasmosis if sulfonamide allergy
What are the ADRs of clindamycin?
Allergic reaction
Diarrhea
C. diff
Hepatotoxicity
What is the MoA of Chloramphenicol?
Reversibly binds to the larger 50S subunit of the 70S ribosome
What has to happen for chloramphenicol to be active?
Must be hydrolyzed in the intestines
IV form has incomplete hydrolysis - 70% serum concentrations of oral
How is chloramphenicol distributed/metabolized?
Excellent CSF concentrations - 30-50% w/o inflammation
Metabolism via glucuronidation in the liver
Wide variations in metabolism and excretion in children
What is the spectrum for chloramphenicol?
Gram positive and negative
Aerobes and Anaerobes
Rickettsia/Chlamydia
What are the ADRs for chloramphenicol?
Hematologic - reversible bone marrow depression (anemia, leukopenia, thrombocytopenia)
Idiosyncratic aplastic anemia
What are the indications for chloramphenicol?
Bacterial meningitis (H. influenza, Strep pneumo, N. meningitidis
Rickettsial infections
