Protein Inhibitors Flashcards
Aminoglycosides (Gentamicin, amikacin, neomycin, streptomycin)
Mechanism: Bactericidal. Prevents formation of initiation complex, causing misreading and early termination of translation
Spectrum: Gram- aerobic
Resistance: Mutations on 30S subunit, or expression of ribosomal methyltransferases. Can also gain enzymes that inactivate the drug via acetylation, etc.
Adverse Effects: Nephrotoxicity, ototoxicity, teratogen (hearing loss in fetus)
Other facts: Administer by IV
Linezolid
Mechanism: Bacteriostatic. Inhibits protein synthesis by binding to ribosomal RNA on 50S subunit, preventing initiation complex
Spectrum: Treatment of drug resistant Gram+, including MRSA
Resistance: Modifications in rRNA, with no cross resistance
Adverse effects: Bone marrow suppression
Tetracyclines: Tetracycline, doxycycline, minocycline
Mechanism: Bind to 30S subunit and prevent attachment of aminoacyl tRNA
Spectrum: Broad initially, but B. burgdorferi, H. pylori, mycoplasma pneumoniae are resistant
Resistance: Increased efflux, alteration of ribosomal target, acetylation
Adverse effects: Chelates with metal ions, gastrointestinal irritation and photosensitivity, discoloration of teeth and inhibits bone growth in children, DONT USE IN PREGNANCY
Chloramphenicol
Mechanism: Binds to 50S peptidyltransferase and can’t associate with amino acid substrate
Spectrum: Extended, but severe side effects limit use
Resistance: acetyltransferase modifies drug to prevent binding
Adverse effects: TOXIC. Bone marrow depression and aplastic anemia. Causes gray baby syndrome in infants
Macrilides: Erythromycin, azithromycin, clarithromycin
Mechanism: Bacteriostatic. Inhibits translocation by binding to rRNA of 50S subunit
Spectrum: Broad. Respiratory pathogens and Chlamydia
Resistance: Methylation of binding site, increased efflux, hydrolysis of macrolide
Adverse effects: GI discomfort, hepatic failure, inhibits Cytochrome P450 enzymes. Not safe for pregnancy
Lincosamide: Clindamycin
Mechanism: Bacteriostatic Blocks translocation at 50S subunit
Spectrum: Gram+ including anaerobic. Treats acne.
Resistance: mutation of ribosome, methylation of rRNA
Adverse effects: Hypersensitivity with rash and fever, diarrhea, abdominal pain, mucus and blood and stool. Causes C. Diff infection!
Streptogramins: Quinupristin/Dalfopristin
Mechanism: Binds to 50S to inhibit translocation
Spectrum: Reserved for infections caused by multi drug resistant G+
Resistance: Methylase prevents binding to target, enzyme inactivation, efflux pump
Adverse effects: Arthralgia and myalgias are common, inhibits CP450
