Antibiotics: Protein Synthesis Inhibitors Flashcards
Selective toxicity:
Describes the phenomenon where a compound causes toxicity to one group of organisms (i.e., bacteria) without creating toxicity to another group (i.e., humans), due to various structural and functional differences.
Aminoglycoside (gentamicin, streptomycin, tobramycin, and amikacin) mechanism of action:
Bind to both the 30S subunit (18S) and 50S subunit (23S) of the bacterial ribosome. It leads to: misreading of the mRNA, blocking initiation (STREPTOMYCIN), blocking translocation (30S binding), and inhibiting recycling (50S binding). They are the only BACTERIOCIDAL protein synthesis inhibitors, due to the production of mutated proteins.
Aminoglycoside resistance:
Multiple enzymes are capable of inactivating these compounds (often by adenylation, phosphorylation, or acetylation). There are other, rarer mechanisms of inactivation.
Aminoglycoside spectrum:
Aerobic GNRs, GPs (synergy with penicillins). ANAEROBES ARE RESISTANT.
Aminoglycoside pharmacokinetics:
Parenteral administration.
Renal excretion.
Significant post-antibiotic effect (GNs only).
Aminoglycoside side effects:
NEPHROTOXICITY (acute tubular necrosis), OTOTOXICITY, rashes, bone marrow suppression, muscle weakness.
Aminoglycoside dosing:
Concentration-dependent killing (CDK) rather than time-dependent killing (TDK). Thus, one should administer a SINGLE, ENORMOUS dose rather than multiple smaller doses (except in patients with renal problems).
Tetracyclines (doxycycline, teracycline, minocycline) mechanism of action:
Binds to 30S subunit, and blocks aminoacyl-tRNA binding, resulting in elongation block.
Tetracycline resistance:
Reduced cell permeability and increased efflux pump expression. Other rarer causes also exist.
Tetracycline spectrum:
Mycoplasma, chlamydia, legionella, rickettsia, borellia, and Strep pneumo. Also used for malaria prevention.
Tetracycline pharmacokinetics:
Reduced gut absorption with food and chelators. Good tissue penetration. Mainly hepatic metabolism.
Tetracycline toxicity:
GI problems, hepatotoxicity, SKIN PHOTOSENSITIVITY. Deposits in teeth and bones of neonates and children, so don’t give to them or pregnant women.
Macrolide (azithromycin, clarithromycin) mechanism of action:
Binds to and blocks the polypeptide release channel on the 50S subunit.
Macrolide resistance:
Efflux, reduced permeability, modification of the 23S rRNA (nucleotide 2058), production of esterase by Enterobacter.
Macrolide spectrum:
GPC, mycoplasma, legionella, chlamydia, H. flu, mycobacteria. Used clinically for RESPIRATORY TRACT INFECTIONS.
Macrolide pharmacokinetics/toxicity:
Azithromycin half-life = 68 hours. Hepatic metabolism. May cause allergic reaction (rash), hepatitis, GI upset, and OTOTOXICITY (especially in the elderly).
Clindamycin (a lincosamide) mechanism of action:
Binds to the 50S subunit (23S rRNA) and interferes with peptide bond formation. Binding site partially overlaps with macrolide binding site.
Clindamycin resistance:
Mutual interference if co-prescribed with the macrolides. Same resistance mechanisms as macrolides (efflux, reduced permeability, modification of 23S rRNA).
Clindamycin pharmacokinetics/spectrum:
GPCs, ORAL AND BOWEL ANAEROBES. Often used for deep seated infections (intra-abdominal infections), skin and soft-tissue infections, dental infections.
Good tissue penetration, concentrated intracellularly.
Clindamycin toxicity:
Hypersensitivity (skin rashes), GI upset, PSEUDOMEMBRANOUS COLITIS, hepatitis, bone marrow suppression.
Linezolid mechanism of action:
Binds 23S rRNA (50S subunit) at the A-site and blocks formation of the initiation complex.
Linezolid resistance:
Mutation of 23S rRNA. No cross resistance with other drug classes.
Linezolid spectrum:
GPC (staph, enterococci, strep), VRE, VRSA, MRSA.
Linezolid toxicity:
Leukopenia, thrombocytopenia, aplastic anemia. GI upset, hepatitis.
