Drugs- protein syn inhibitors Flashcards
Tetracyclines
spectrum:
mech of action:
very broad spectrum
Enter gram (-) bacteria by diffusion thru porins
Minocycline and Doxycycline more lipophilic and cross outer membrane, great affinity for gram -
Mech: Bind 30S subunit of ribosome, preventing access of aminoacyl tRNA to acceptor (A) site on mRNA-ribosome complex
Tetracyclines: Mech of resistance
Numerous, important ones are:
- decreased influx into bacteria thru altered membrane porin proteins
- increase efflux thru actice transport out of cell by pump proteins
Tetracyclines
absorption:
Distribution:
elimination:
administration methods:
absortion: dairy products and divalent cations interfere
Distribution: distribute to bones and teeth, can cross placenta where they can stain developing teeth
elimination: glucuronidation, with urinary excretion (most) and minor biliary excretion
EXCEPT: doxycycline is almost entirely excreted in bile, safe in renal failure
Doxycycline PO and IV
Minocycline and tetracycline PO only
tetracycline adverse effects
gastric discomfort: irritating mucosal tissues (gastritis, esophagitis)- remain upright 45-60 min after dose.
Bone/teeth: may interfere with bone depostition; stains teeth (dont use before age 9)
Phototoxity: skin rashes with light exposure
Vestibular problems: dizziness with minocycline
Associated with liver failure at high dose, and in pregnancy
super infection
Uses of tetracyclines
Pneumonia “atypical pathogens”
STDs (Chlamydia, PID, LGV)
Rickettsial infection
Prophylaxis against malaria
CA-MRSA
P.Acnes
Tigecycline
mech:
administration:
spectrum:
uses:
Bacteriostatic inhibitor of 30S ribosome, blocking aminoacyl-tRNA
IV only (hospital infections only)
Broad spectrum of Action
Gram + (including MRSA and VRE)
Gram - (includes MDR acinetobacter, excluding Pseudomonas)
Anaerobes
Indicated for soft tissue infection, complicated intraabdominal infection, CA pneumonia
Recent warning about increased mortality for nosocomial pneumonia
Aminoglycosides
mech of action:
from a mold
First bind to outer membrane, displacing cations
causes disruption of outer membrane
Transport across cytoplasmic membrane
- depends on electrochem enviroment
- gradient depends on oc phos
- No gradient in anaerobic condition
- not active in abcesses
Once inside bacterial cell, disrupt translation:
- bind 30S ribosome (primarily)
- interfere with formation of initiaition complex
- cause misreading of mRNA, missence mutations, incorporation of wrong amino acid
- interfere with translocation
Aminoglycoside activity pharmodynamics
Exhibit concentration dependent killing: bacteriacidal activity is proportional to peak concentration
Post antibiotic effect is prolonged (10 hrs)
Toxicity is less with once daily dosing
Multiple dosing may be needed to achieve synergy with cell wall active agents
Aminoglycosides
spectrum of action:
effective primarily against aerobic gram - bacteria including pseudomonas
- amikacin>tobramycin>gentamicin
Some acitivity against gram +
- most strep, staph
- used with penicillin or vancomycin in synergistic regiment for enterococcal, and some staph infections
Macrolides : adverse events
adverse drug interactions:
epigastric distress, greatest with erythromycin
Cholestatis jaundice
Ototoxicity (rare, transient, seen in high doses)
Cardiac conduction: QT prolongation
Contrainications: hepatic dysfunction
Adverse drug interactions
- interfere with cytochrome P450 clearance
- Theophylline, cyclosporin, digoxin, others
Linezolid
mech:
sprectrum:
First and onlye member of oxazolidinone class
interferes with intiatiation of translation, preventing formation of 70s comples
Active against S. aureus (inclduing MRSA), strep, enterococcus faecium, enterococcus faecalis including VRE strains
Linezolid
pharmcokinetics:
adverse events:
pharmokokinetics: very well absorbed orally, BID dosing (IV, PO)
85% excreted in urine
Adverse effects: diarrhea, nausea, vomiting
bone marrow suppression (usually platelets after ~2 wks)
Weak MAO inhibitor (can cause serotonin syndrome with SSRIs, maybe fatal)
Protein synthesis inhibitors key points:
tetracyclines:
aminoglycosides:
chlorampheicol:
macrolides:
clindamycin:
- *Tetracyclines**
- Widely available, wide spectrum, resistance common, bacteriostatic
- *Aminoglycosides**
- Active against aerobic organisms only; usually bactericidal
- Oto-, nephrotoxic
- Used in synergistic therapy for enterococci
- *Chloramphenicol**
- Seldom used in the U.S. due to hematopoetic toxicities, very broad spectrum
- *Macrolides**
- Broad spectrum, respiratory tract and skin infections
- Erythromycin causes most GI upset
- *Clindamycin**
- Spectrum: anaerobic bacteria and gram + (including CA-MRSA)
- Classic pseumomembranous enterocolitis risk
Drugs with anaerobic infections:
Protein synthesis inhibitors:
Clindamycin
Chloramphenicol
Tigecycline
Beta-lactamase inhibitor/penicillin combinations:
Penicillins
Piperacillin/tazobactam
Ampicillin/sulbactam
Amoxicillin/clavulanate
2nd gen cephalosporins (cefoxitin, cefotetan)
Carbapenems
Moxifloxacin (fluoroquinolone)
Metronidazole
- NOT A PROTEIN SYN INHIBITOR
Acts as an electron acceptor; once activated by reduction, it damages DNA and other macromolecules
Very well absorbed orally. Available IV and PO.
Penetrates well into all tissues.
Highly bactericidal for anaerobic bacteria, no activity against other Gram + or Gram -
Also used to treat wide array of protozoans
Trichomoniasis, Giardiasis, Amebiasis
- *Disulfiram-like** reactions with alcohol.
- *Sensory neuropathy** with prolonged use.
