antibiotics for osteomyelitis and skin infections med chem Flashcards
tetracycline drugs
tetracycline
monocycline
doxycycline
tigecycline
tetracycline MoA
interacts with 30S subunit of ribosome and sits in A site to prevent elongation (bacteriostatic)
tetracycline general pharmacophore
4 rings and dimethylamine pointing into the board
ways to inactivate tetracyclines
- make dimethylamine come out of the board
- dehydration of OH on north side
- breaking C ring through intramolecular reaction
avoid taking tetracyclines with what
multivitamins and milk because of chelation with ions
tetracyclines clinical use
- Gm+
- MRSA
- limited Gm-
tetracycline resistance
widespread in forms of
- efflux
- mutations in ribosome
- cell wall variation
side effects of tetracyclines
- light sensitivity
- severe kidney damage
- incorporation into bones and teeth
tigecycline unique structure feature
the claw on the tetracycline ring that prevents efflux based resistance
tigecycline clinical use
broad spectrum, typically saved for instances of resistance
hits basically everything but pseudomonas
clindamycin MoA
sits in 50S peptidyltransferase to inhibit the enzyme
clindamycin clinical use
- Gm+ (staph, strep)
- used w/ aminoglycosides for Gm-
- some anaerobes
- used if PCN allergy
- PO/IV
clindamycin side effects
- GI
- pseudomembranous colitis caused by C.difficile
linezolid MoA
prevents formation of 70S subunit complex by binding w/ 50S subunit
linezolid clinical use
- Gm+
- MRSA
- VRE
- IV/PO
linezolid resistance
still rare but can be seen as:
- point mutation of ribosome
- efflux pump in Gm-
linezolid side effects
- monoamine oxidase inhibitor, so avoid w/ tyramine foods and serotonergic drugs
- bone marrow suppression
linezolid monitoring
weekly blood counts
synercid
- IV only
- combo of dalfopristin and quinupristin
- 30:70 ratio quinupristin:dalfopristin because dalfo binding first increases affinity for quinupristin
synercid MoA
binds to A and P sites to interfere with tRNA binding and misalignment of P site
mupirocin MoA
binds to Ile-tRNA synthetase to prevent incorporation of Ile into proteins
mupirocin clinical use
- used topically or nasally because it is hydrolyzed in vivo
- broad spectrum activity, good against staph and strep
mupirocin resistance
mutations in synthetase enzyme prevents binding
vancomycin MoA
“hugs” cross link area of peptidoglycan to prevent transpeptidase cross link AND prevents sugars from cross linking
vancomycin clinical use
- narrow spectrum Gm+
- used for C.diff and enterococci
- last resort for MRSA
- PO/IV
vancomycin resistance
D-Ala D-Ala becomes D-Ala D-Lactate to reduce hydrogen bonding
vancomycin resistant enterococci background
- 2nd most common Gm+ in hospitals
- high moretality
treatments for VRE
synercid
linezolid
cubicin (daptomycin)
linezolid route
oral and IV
clindamycin route
oral
tigecycline route
IV
telavancin and dalbavancin MoA
- disrupts peptidoglycan cross linking
- long FA chain anchors it in membrane helping with affinity
telavancin route
IV
dalbavancin route
IV
telavancin and dalbavancin clinical use
- MRSA
- some vancomycin resistant strains
difference between telavancin and dalbavancin
half life
dalbavancin has once weekly dosing
daptomycin MoA
creates a potassium ion channel leading to membrane depolarization
daptomycin clinical use
Gm+ -resistant strep -resistant staph -resistant entero MRSA VRE -IV
daptomycin side effects
- elevated serum creatinine phosphkinase
- rhabdomyolysis
daptomycin monitoring
signs of muscle pain or weakness
tetracyclines contraindications
- pregnant females
- children under 8
vancomycin IV side effects
- GI
- red man syndrome
