protein synthesis inhibitors Flashcards
what are the protein synthesis inhibitors?
30s: tetracyclines, aminoglycosides
50s: Macrolides, Clindamycin, Streptogramins, Oxazolidinones
doxycycline excretion: renal?
not renal - hepatic and fecal
Tetracycline: MOA, Spectrum, bactericidal or static?
Bacteriostatic MOA: 30s subunit (protein) spectrum: BROAD (+ and -). -atypicals: ricksettsia (ticks, mites, fleas, lice), chlamydia, mycoplasmic pneumoniae -spirochete: lyme disease
tetracycline resistance
3 possible ways:
- efflux pump (bacteria expels drug out of cell)
- enzymatic inactivation
- bacteria proteins that prevent binding of drug to ribosome
- resistance to one tetracycline DOES NOT mean to resistance to all
Additions to spectrum of tetracyclines: doxycycline and minocycline
doxy: atypical: CAP, malaria, prophylaxis
mino: P. Acnes
PK of tetracyclines
Oral administration Absorption decreased by: Divalent cations ( Ca, Fe, Mg or Al) Diary products Antacids (don't take with these) =reduced bioavailability when with foods
poor CNS penetration
super infection can occur with what type of antibiotic?
any broad spectrum (most often cause is candida or Cdiff)
serious adverse effects of tetracycline
Skin: photosensitivity Staining of teeth Bind to calcium deposited in newly formed bone or teeth in young children and fetal teeth during pregnancy Teeth fluorescence/discoloration Enamel dysplasia
Fetal bone deformities
Deposit in bone leading to deformity or growth inhibition
CONTRAINDICATED in pregnant women, infants, children < 8 years or younger
“TETRAcycline = TERATogenic”
Glycycline –> tigecycline
Tetracycline derivative (semisynthetic of minocycline)
(IV drug)
MOA: 30s subunit
Spectrum: BROAD (+ and -) including MRSA, VRE
anaerobes
atypical- legionella (CAP)
clinical uses: CAP, infections of deep tissue and intra-abdominal
aminoglycosides
"GNATS" - all "mycin" except Amikacin Gentamycin Neomycin Amikacin Tobramycin Streptomycin
post antibiotic effect is most common in what type of abx?
those that inhibit protein/DNA/RNA.
PAE- suppression of bacterial growth after brief drug exposure
PK of aminoglycosides: Absorption, distribution, elimination
abs: only IV (occassional IM) or topical (conjunctivitis)
- hospital drug
distribution: good, no CSF or eye (unless topical) but can use for meningitis with other drugs if inflamed and synergistic (beta lactams)
elimination: renal, MUST make dose adjustment w/ kidney failure. (monitor serum drug levels )
aminoglycosides are good to treat what?
gram neg serious infections: bacterial meningitis, sepsis, (endocarditis), osteomyelitis, etc)
aminoglycosides adverse effects
ototoxic, nephrotoxic, neuromuscular blockade
triple antibiotic ointment
neomycin (gram- and gram +, too nephrotoxic for oral or IV- hence ointment)
polymixin (gram -)
bacitracin (gram +)
“mean GNATS caNNOT kill anaerobes”
mean (aminoglycosides)
GNATS: gentamycin, neomycin, amikacin, tobramycin, streptomycin
NNOT: nephrotoxicity, neuromuscular blockade, ototoxic, teratogen (oto and nephro for fetus too)
erythromycin is used mostly for what?
acne (only macrolide that is bacteriostatic instead of cidal
fidaxomicin use for?
MOA, spectrum, adverse
Cdiff but VERY expensive
MOA: thought of as macrolide but binds to RNA polymerase and stops protein binding
Spectrum: NARROW- CDiff (gram +)
Adverse: bowel obstruction or GI hemorrhage
macrolides
“FACE” fidaxomycin, azithromycin, clarithromycin, erythromycin
..or girls names - “FrIDA, AZI, CLARe, ERYn”
macrolide MOA and spectrum
MOA: 50s subunit
spectrum: gram + cocci
atypical pneumonias
chlamydia, mycoplasma, legionella(CAP)
macrolides- drug resistance patterns
primarily why we dont use erythromicin anymore
- target modification- prevent abx to ribosome bind
- efflux
- drug inactivation
z pack
axithromycin: - LONG half life- different Dosing - “Zpack” - pt only takes for 5 days but actually stays in system for 10 days - increases pt compliance
EASIER IS BETTER -
macrolide excretion
bile and feces
generally use macrolides for what clinical uses?
STIs and CAP
adverse effects of MACROlides
"MACRO" GI Motility (usual stomach upset) Arrhythmia acute Cholestatic hepatitis Rash Eosinophilia
- erythro and clindo are worst for these, Azithromycin is best to use to limit adverse effects
- first 2 most important
Erythromycin and Clarithromycin have what significant danger?
drug interaction- inhibit CYP34A - increases serum levels of other drugs (esp. statins and warfarin)
treatment of anerobes above and below diaphram
above: clindamycin
below: metronidazole
abx most common cause of superinfection Cdiff
Clindamycin and fluoroquinolones
Clindamycin: MOA, Bactericidal?, Spectrum
MOA: 50s subunit (tunnel)
bacterioSTATIC
spectrum: gram + cocci (strep and staphy) MRSA, MSSA
anerobes- above diaphragm
adverse effects of clindamycin
superinfections Cdiff
streptogramins: combo of what? MOA, bactericidal?, spectrum
daflopristin/quinupristin (synercid)
MOA: 50s subunit
bactericidal?: yes- conc dependent
spectrum: FOR LIFE THREATENING VRE
what do you take for life threatening VRE?
streptogramin: dafl/quinu- pristin
1st choice for MRSA
vancomycin
1st choice for MSSA
PCN antistaph or Trimethoprim “Anti Staph: MiSSA, TriMe”
oxazolidnones: drugs in group, MOA, bactericidal?, spectrum
tedizolid and linezolid (more common one)
MOA: 50s subunit
bactericidal?: no STATIC
spectrum: multi-drug resistant gram + (VRE, MRSA)
…also HAP and CAP
Buy AT 30, CEL at 50
protein synthesis inhibitors
30: Aminoglycosides and Tetracyclines
50: Clindamycin, Erythromycin (macrolides), Linezolid (oxazolidnones)
protein synthesis inhib: cidal or static?
static at low doses, cidal at high doses
