Protein Synthesis Inhibitors Flashcards
Protein synthesis inhibitors 7
Aminoglycosides Macrolides Tetracyclines Chloramphenicol Clindamycin Linezolid Streptogramins
Aminoglycosides 5
Gentamicin Neomycin Amikacin Tobramycin Streptomycin
Aminoglycosides MOA
Bind bacterial ribosome at 30S
Misreading of genetic code-> some of misread proteins go to cell membrane, make it more permeable to salt and water—> cell death
Aminoglycosides are bacteriocidal
Require O2 for tx into cells- NOT FOR ANAEROBES
NOT TRANSFERRED INTO CELLS NOT EFFECTIVE FOR INTRACELLULAR ORGS (rickettsia, chlamydia)
Aminoglycosides use
Streptomycin used in combo for M. Tb
Neomycin preop for bowel surgery- poorly absorbed, give with erythromycin
Aminoglycosides + beta lactam synergy
Combo more effective than sum of either alone
Vancomycin/gentamicin for endocarditis
Ampicillin/gentamicin for newborn meningitis
Pip/tazo + tobramycin for CF pts with pseudomonas
Aminoglycoside resistance
Aminoglycoside modifying enzymes - bacteria acquire enzymes that modify drug structure, modified structure binds poorly to ribosomes
Aminoglycoside kinases- phosphorylation
Transferases- adenylation/acetylation
Aminoglycosides AES
Ototoxicity
Nephrotoxicity- ATN
Neuromuscular blockade- can block/limit ACh release at NMJ
CANNOT USE IN PREGNANCY
Macrolides
Azithromycin
Clarithromycin
Erythromycin
Macrolides MOA
Bind 50s ribosome and block translocation
Macrolides uses
GP, especially strept
Some GN
Concentrated in macrophages and cells EFFECTIVE AGAINST INTRACELLULAR PATHOGENS - Chlamydia (obligate) - Legionella (facultative) — both are good for atypical PNA
Community acquired PNA
Safe in pregnancy
Gonorrhea tx
Macrolide + ceftriaxone
Chlamydia and gonorrhea often coninfect
Macrolides in GI infection
Erythromycin- binds motillin receptors, stimulates smooth muscle contraction, can be used in GI motility dx
Clarithromycin- part of triple tx for H pylori
Macrolide resistance
Methylate abx binding site on 50s ribosome
Macrolide AEs 5
N/V/D
QT prolongation
Acute cholestatic hepatitis
- contraindicated for pts w liver dysfunction
Maculopapular rash
P450 ENZYME INHIBITORS
- raise warfarin and theophylline levels
Tetracyclines
Tetracycline
Doxycycline
Demeclocyline
Minocycline
Tetracycline MOA
Bind 30s ribosome
Demeclocycline use
Not used as abx
ADH antagonist- treat SIADH
Causes nephrogenic DI to reverse SIADH
Doxycycline use
MC used in tetracycline family
Accumulates intracellularly
Covers zoonotic and atypical bacteria (chlamydia)
Treats acne vulgaris (minocycline)
Tetracycline absorption impaired by
Minerals and antacids
Calcium, magnesium, iron, dairy
Chelate the drug
Cannot be taken with antacids or milk
Tetracycline resistance
Decrease influx or increase efflux
Plasmid encoded transport pumps
Tetracycline AEs
GI distress Photosensitivity DO NOT GIVE TETRACYLCINES TO KIDS: Discoloration of teeth Inhibit bone growth in peds CONTRAINDICATED IN PREGNANCY
Chloramphenicol MOA
Inhibits peptidyl transferase at 50s ribosome
Chloramphenicol use
Rickettsia and ehrlichia in pregnancy- only 1 and 2 trimester
Meningitis in developing world
- less effective but cheap
Chloramphenicol AEs
Aplastic anemia- irreversible, fatal
Gray baby syndrome- infants lack liver enzyme to metabolize drug-> skin turns GREY, hypotension, fatal
Clindamycin MOA and resistance
Same as macrolides:
Binds 50s ribosome
Methylation of abx binding site
Clindamycin use
Anaerobes above diaphragm:
Aspiration PNA
Lung abscesses
Oral infections
B fragilis highly resistant to clindamycin, use metronidazole
Clindamycin AEs
C diff—> pseudomembranous colitis
Antibiotic assoc diarrhea- milder than c diff, osmotic diarrhea
Linezolid MOA and use
Binds 50s ribosome
Vancomycin resistant enterococcus (VRE)
Linezolid AE
Serotonin syndrome- linezolid is monoamine oxidase inhibitor
High risk if given with SSRI
Serotonin syndrome- fever, confusion, agitation, hyperreflexia
Streptogramins
Quinupristin/dalfopristin
Streptogramins MOA and use
Block 50s ribosome
Used for vancomycin resistant bacteria- VRSA, VRE
What protein synthesis inhibitor abx are bacteriocidal?
Aminoglycosides
- misread proteins travel to membrane and increase permeability
All others are bacteriostatic
