Protein Synthesis Inhibtors Flashcards
What are the two families of 30 S inhibitors
(list bacteriostatic or bacteriocidal)
Aminoglycosides (cidal irreversibly bind)
Tetracyclines (bacteriostatic reversibly bind)
What are the four families of 50S inhibitors
(list bacteriostatic or bacteriocidal)
Macrolides (bacteriostatic)
Clindamycin (bacteriostatic)
Chloramphenicol (bacteriostatic)
Quinupristin-Dalfopristin
List 5 Aminoglycoside drugs
Tobramycin
Amikacin
Neomycin
Gentamicin
Streptomycin
aminoglycosides are more effective aginst what than any other antibioitc class
why then are they not always used for that?
Gram negative aerobes
often times are more toxic then alternatives so are saved for serious infections resistant to those less toxic drugs
Aminoglycosides are only effective against ____ class when combined with ____
Few gram pos organisms
when combined with CWSI’s
What group of organisms are aminoglycosides not effective against and why
anaerobes
because they requrie oxygen dependent transport process to enter the cell
what is the chemistry of aminoglycosides and what does that mean about their absorption
they are amino sugars meaining they are extensively ionized in acidic fluids
This means poor bioavailability when administered orally so
must be given parenterally for systemic infections
Can be good orally for gi infections (because trapped in gi)
Can be used topically for skin mucous membranes and ocular tissues
What drug are aminoglycosides used in combo with and why
CWSI
allows the ag to enter the bacteria and synergistically allows more activity against both gram postive and gram negative
What is the main route and time of elimination of aminoglycosides
Glomerular filtration primarily
Half life 2-3 hours
Which aminoglycosides can be used in a TB infection
Streptomycin and Amikacin
Which populations would need to avoid Aminoglycosides
Pregnant women (pregnancy category D drug)
Individuals with low creatinine clearance
What is the mechanism by which drugs become resistant to Aminoglycosides
Bacterial acetylase, adenylase, and phophorylase enyzmes
(degrade the aminoglycoside and prevent its binding to its site)
(could also decrease drug accumulation through porin mutation)
(could also alter target site to decrease the binding to the 30S ribosome)
Which aminoglycoside is more resistant to bacterial resistance mechanism
Amikacin
( it is protected at more sites than gentamicin and tobramicin)
List 4 major adverse effects of aminoglycosides
- Nephrotoxicity
- causes tubular necrosis by accumlating in renal cortical cells
- usually reversible
- Ototoxicity
- accumulates in peri/endolymph of the ear when AG levels are elevated, can be irreversible
- Levels must be adjusted/monitored closely to prevent toxicity
- single daily dosing
- Toxicity increased in combo w/ other nephrotoxic or ototoxic agents
define the mechanism of action of the aminoglycosides and the tetracyclines
Aminoflycosides: bind to the initiations site of the 30s and prevent formation of the initiation complex
Tetracyclines: inhibits the binding of tRNA to the A site of the 30S ribosome
how are tetracyclines absorption affected and how are they distributed
- Absorption affected by Food
- Tetracyclines: all foods decreas absorption
- Doxy and Minocycline: food DOES NOT decrease absorption
- Absorption Decreased by polyvalent Cations (dairy, calcium, iron, antacids)
- Distirbution: well distributed but does not cross BBB (except Minocycline)
How are teetracyclines eliminated
Tetra and Mino: Renal and Biliary
Doxy: Biliary
what are the main adverse effects of tetracyclines (6)
- Concentrates in growing teeth and bones (contra in kids less than 8 and pregnant women-category D0
- Allergi Reactions
- Dermatologic (phtosensitivity-accum in skin hyperpigmentation with minocycline)
- Hepatotoxicity (fatty liver- high incidence in pregnancy)
- Ototoxicity (minocycline)
- GI issues
- GI upset N/V/D (less for mino and doxy
- GI flora
- superinfecctions and drug drug interactions
- May make oral contraceptives less effective
what are the main mechanisms of resistance against tetracyclines
Decreased Drug accumulation
Altered Target site
Enzymatic drug inactivation
Important resistant organism: Psuedomonas
what are 2 main similarities and 2 main differences between the tetracyclines
- Similarities
- antimicrobial spectrum
- all bind divalent and trivalent cations so their avialability is dec with food containing cations
- Differances
- oral bioavailability
- 70% tetracycilnes (10 hr half life)
- >90% doxy and mino (15 and 19 respectively)
- intensity of adverse effects
- tetra has most effect on teeth and bone
- doxy has most photottoxicity
- mino has most ototoxicity (and is only one to cross bbb)
- oral bioavailability
what are the similarities and differences between tigecycline and tetracyclines
similar
Chemistry and pharmacokinetics to tetracyclines
differences
parenteral only
longer half life (27-42 hours)
biliary excretioon
Binds with affinity 5x that of tets (though to same region of the 30S
NO OTOTOXicity
