Protein Synthesis Inhibitors Flashcards
What are the protein synthesis inhibitors and what do they target?
30S Inhibitors
Aminoglycosides (cidal)
Tetracyclines (static)
50S Inhibitors
Chloramphenicol, Clindamycin (static)
Erythromycin (macrolides) (static)
Linezolid (variable)
buy AT 30, CCEL at 50
What are the Aminoglycosides?
MOA?
SE?
Resistance
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Inhibit 30S Cidal
Block formation of initiation complex and cause misreading of mRNA, and translocation
Need O2 for activation
Severe g- rods, synergistic with B lactam, neomycin for bowel surgery
Resistance: Bacterial transferase by slapping an acetyl, P04 or adenylation on to the drug making it inactive
SEs: Nephrotox esp with Cephalos
Neurotics block
Ototox esp with loops
Teratogen
Tetracyclines MOA Use SE Resistance
Tetra, Doxy, Mino
Static: Bind to 30S and prevent attachment of Aminoacyl-t-RNA. Can accumulate intracellularly so good for intracellular bugs
Doxy fecally eliminated so renal patients ok
DONT TAKE WITH MILK OR ANTAACIDS bc they block their absorption in the gut (Mg and Ca)
Use for Borrelia, Mycoplasma
SEs: Discoloration of teeth, GI distress, decreased bone growth in kids
Resistance: Pumped out of bugs by plasmid encoded transport pumps
Macrolides MOA Use SE Resistance
Static…Azithromycin
Clarithromycin
Erythromycin
Bind to 23S rRNA of 50S, blocking translocation (macroslides) and inhibiting protein synthesis
Use: Atypicals (chlamydia, mycoplasma Legionella) STD and g+ cocci esp for ppl allergic to penis
SE: MACRO Motility in GI Arrythmia (prolonged QT) Cholestatic hepatitis Rash eOsinophilia
P450 Inhibitors; incr serum conc of theophylline and anticoags
Resistance: Methylation of 23S sRNA binding site so drug can’t bind there
What is Chloramphenicol?
Use?
SE?
Resistance?
MOA:
Blocks PEPTIDYLTRANSFERASE at 50S subunit.
Bacteriostatic
Meningitis and Rocky Mountain spotted fever
SE: Anemia, Aplastic Anemia, GREY BABY SYNDROME bc they don’t have Liver UDP-GLUCORONYL TRANSFERASE
Resistance: Plasma encoded acetyltransferase inactivates drug
Clindamycin?
MOA
Use
SE
MOA Blocks Peptide (translocation) at 50S. Bacteriostatic
Anaerobes above the diaphragm
(Metro does anaerobes below diaphragm)
Anaerobes in oral cavity, aspiration pneumonia, lung abscesses.
Also Group A strep infection
SE: Allows for C. Diff overgrowth, fever, diarrhea
What are the sulfonamides?
MOA
USE
SE
Sulfamethaxole (SMX)
Sulfisoxazole
Sulfadiazine
MOA:
Inhibit Folate synthesis
PABA antimetabolites inhibit dihydropteroate synthase. Bacteriostatic
Use: Gram-/+, Nocardia, Chlamydia
SE: HSRs Hemolysis if G6PD deficient Nephrotox (tubulointerstitial nephritis) Photosensitivity Kernicterus in infants Displace other drugs from albumin, i.e. warfarin
Resistance:
Altered Dihydropteroate synthesis, Decreased uptake or increased PABA synthesis
Trimethoprim (TMP)
MOA
Use
SE
Inhibits bacterial DHF; Bacteriostatic
Used in combo with Sulfonamides
Causes sequential block of folate synthesis
Use:
UTI, Shigella, Salmonella, Pneumocystis, Toxoplasmosis for treatment and prophylaxis
SE: Megaloblastic anemia, leukopenia, granuloctyopenia
Give with folinic acid to to alleviate SEs
TMP = Treats Marrow Poorly
What are the fluoroquinolones? MOA Use SE Resistance
All of the “floxacins” i.e. Ciprofloxacin, norfloxacin, Nalidixic acid (a quinolone)
Inhibit DNA gyrase (topo II and IV)
DO NOT GIVE WITH ANTACIDS
Use: G- of UTI and GI infections (pseudomonas, Neisseria, some g+
SEs: Can’t tiptoe on Cipro, or any of the others…tendon rupture, esp old people taking prednisone. Also rash, dizziness, superinfections
Contra in preggos, or children due to cartilage damage
Prolonged QT in some
Resistance: Efflux pumps, mutated gyrase, plasmid mediated resistance
What is metronidazole?
MOA
Use
SE
Forms free radical toxic metabolites that damage bacterial DNA; Bactericidal, anti-protozoal
Use: GET GAP on the metro with metronidazole
Giardia
Entamoeba
Trichomonas
Gardnerella
Anaerobes (Bacteroides, C. Diff)
Pylori (part of triple therapy with clarithromycin)
Treat anaerobe infections below diaphragm
SE: DISULFIRAM like reaction (severe flushing, tacky, hypOtn) with alcohol, HA, metallic taste
