Protein Synthesis Inhibitors Flashcards
Examples of Tetracyclines?
- Tetracycline
- Doxycycline
- Minocycline
Mechanism of Action of Tetracyclines?
- enter organism by passive diffusion or energy-dependent transport protein
- bind reversibly to 30S subunit of bacterial ribosome, preventing binding of tRNA to A site of mRNA-ribosome complex – inhibiting bacterial protein synthesis
How should tetracyclines be administered?
Absorbed after oral ingestion, best on empty stomach
avoid administration with dairy products (contains calcium) or substances with divalent or trivalent cations - decreases absorption due to formation of non-absorbable chelates
Can tetracyclines cross CSF?
moderately, more for minocycline and doxycycline
For Tetracyclines:
a) route of administration
b) target organisms
c) elimination
d) pregnancy use. why or why not.
a) all oral
b) tetracycline: rickettsia, chlamydia, mycoplasma pneumoniae, vibrio cholerae, yersnia pestis; doxycycline: those covered by tetracycline, acne vulgaris, bacillus anthracis, s. pneumoniae, h. influenzae (CAP), MRSA (soft tissue infections), borrelia burgdorferi (Lyme disease); minocycline: those covered by tetracycline, h. influenzae, klebsiella
c) tetracycline by kidney; doxycycline by bile and urine; minocycline: liver
d) Category D (NO)
What drug was designed to overcome tetracycline resistance? What two mechanisms of resistance does it overcome? Mechanism of Action?
Tigecycline
- Efflux pumps + Ribosomal Protection
same mechanism of action as tetracyclines
For Tigecycline,
a) Route of Administration
b) Penetration into tissues + CSF?
c) Elimination?
d) Pregnancy use?
e) Target Organisms?
a) IV
b) Well into tissues, low plasma concentration (pls dont use in bloodstream infection); reaches CSF concentrations of 10% of that found in serum with uninflamed meninges
c) Biliary or Fecal
d) Cat D (NO)
e) MRSA, Multidrug resistant Strep, VRE, ESBL, CAP
Adverse effects of tetracycline and tigecycline?
- Gastric Discomfort
- Effects on Calcified Tissues (gives grey teeth) (NO use on oregnant or breast-feeding women or in children <8)
- Hepatotoxicity
- Phototoxicity
- Vestibular Dysfunction
- Renal
- Superinfection = CDAD
What are drug-drug interactions of tetracyclines and tigecyclines?
- Enhance oral sulfonylureas, digoxin, lithium, theophylline
- Reduce efficiacy of oral contraceptives, warfarin
- NO to together with beta lactams
What is the mechanism of action of aminoglycosides?
- diffuse thru porin channels in outer membrane of gram-neg bacteria, transported across inner membrane via active transport
1. Block formation of initiation complex
2. Cause misreading of codons
3. Inhibit translocation
How to enhance entry of aminoglycosides into bacteria?
Cell wall synthesis inhibitors like beta lactams (synergism)
How to inhibit the energy-dependent phase of aminoglycosides entry into bacteria
anaerobic conditions, drop in pH, hyperosmolarity
Names of aminoglycoside antibiotics?
Gentamicin
Tobramycin
Amikacin
Streptomycin
Neomycin
For aminoglycosides,
a) absorption
b) distribution
c) CSF
d) elimination
a) mainly parenteral, except neomycin (oral for bowel prep)
b) variable penetration into most body fluids - dosed based on lean body mass, not actual weight
c) inadequate CSF, even with inflamed meninges
d) renal, neomycin is 97% thru feces
effect of aminoglycosides on pregnant women?
can cross placental barrier and accumulate in fetal plasma and amniotic fluid
for central nervous system infections, how can aminoglycosides be administered. which aminoglycoside?
gentamicin intraventricularly
aminoglycosides are usually used in combination with ____. Why?
Cell Wall active agents.
1. Expand empiric spectrum activity
2. Synergistic Bacterial Killing
3. Prevent emergence of resistance to individual agents
for gentamicin, what are the main organisms is targets?
- proteus, pseudomonas, klebsiella and other MDR gram negs
- combination with penicillin for enterococcal endocarditis (gram pos)
for tobramycin, what are the main organisms is targets?
pseudomonas aeruginosa, alongside anti pseudomonal antibiotics
NO vs enterococci
for amikacin, what are the main organisms is targets?
proteus, p. aeruginosa, klebsiella (2nd line), enterobacter, e coli
m. tb
enterococci (2nd line)
NO vs most other gram pos anaerobic