Mata - antibiotics Flashcards
classes that inhibit DNA synthesis
Sulfonamides
Trimethoprim
Fluoroquinolones
classes that interfere with cell wall
Penicillins Cephalosporins Carbapenems Aztreonam Vancomycin Daptomycin Polymyxins Colistin
b-lactams
Penicillins
Cephalosporins
Carbapenems
Aztreonam
classes that inhibit protein synthesis
Macrolides Clindamycin Chloramphenicol Streptogramins Linezolid Tetracyclines Aminoglycosides Mupirocin
subgroups of Penicillins
Pen G
Pen V
Aminopenicillins (amoxicilin/ampicillin)
b-lactamase resistant (nafcillin/oxacillin)
extended spectrum (ticarcillin/pipercillin)
Penicillins
MOA: b-lactam
bactericidal
Gram + (some gram – cocci)
excretion: renal (except nafcililn)
Pen G limitations
short half-life
narrow spectrum (Gram +)
not acid stable (not orally)
susceptible to b-lactamases
Pen V improved ___ compared to Pen G
absorption
more acid stable, can be given orally
Aminopenicillins
semisynthetic
broader spectrum, includes some gram –
acid stable, used orally
rash more common
Ticarcillin and Pipercillin
extended spectrum
treat more serious gram –
aka anti-pseudomonal penicillins
3 ways to overcome b-lactamase
give more drug
inhibit b-lactamase directly
make changes to drug
nafcillin and oxacillin
b-lactamase resistant
naficillin excretion
biliary
Cephalosporins
MOA: b-lactam
bactericidal
Gram + and – (generations differ)
excretion: renal
1st gen cephalosporins
mainly gram + cocci
some gram –
ex: Cefazolin
Cefazoline used for
prophylactically before surgery, long half life, high protein binding
2nd gen cephalosporins
gram + and -
extended coverage of –
3rd gen cephalosporins
more gram – than +
ex: ceftriaxone
Ceftriaxone uses
bacterial meningitis - Strep pneumoniae and N. meningitidis
crosses BBB
hepatic/biliary elimination
Ceftriaxone precaution
incompatible with calcium containing products
4th gen cephalosporins
gram + and -, for b-lactamase producing bacteria
ex: cefepime
Ceftaroline
advanced generation/newer cephalosporin
bactericidal
for MRSA
patients with history of anaphylaxis to penicillins should not get ___
cephalosporins
________ enter breast milk and may alter bowel flora of the infant
Cephalosporins
___ should not be given to hyperbilirubinemic and preterm neonates because in vitro, can displace bilirubin from serum albumin, potentially triggering kernicterus
Ceftriaxone
Aztreonam
MOA: b-lactam
Gram + (no anaerobes)
does not cross react with penicillin
Carbapenems
MOA: b-lactam resistant to b-lactamases very broad spectrum given IV excretion: renal
Vancomycin
MOA: inhibits cell wall synthesis, high affinity binding to D-Alanyl-D-alanine terminus of cell wall precursor units, no cross bridges formed
Gram +
important for MRSA
oral vancomycin
not orally bioavailable, used to treat C. diff
adverse effects of vancomycin
ototoxicity
nephrotoxicity
hypersensitivity reactions
red man syndrome
Daptomycin
MOA: disruption of bacterial membrane through formation of transmembrane channels
cause leakage of intracellular ions –> depolarizing cell membrane and inhibiting macromolecular synthesis
Gram + only
concentration dependent killing
serious infections, but not in lungs
IV only
excretion: renal
Polymyxins
MOA: bind to and disrupt action of LPS, neutralizing bacteria’s toxicity
Gram –
Colistin
a polymyxin
orally for bowel decontamination
inhaled therapy for CF patients
Macrolides include
azithromycin
clarithromycin
erythromycin
Macrolides
MOA: reversibly bind to 50S subunit at tRNA binding site, inhibit protein synthesis usually bacteriostatic narrow spectrum (gram + and --) oral or IV good for lung infections excretion: bile
erythromycin causes…
dose limiting GI disturbances
used a prokinetic
Adverse effects of macrolides
C. diff colitis hepatitis, hepatic dysfunction QR prolongation torsades de pointes drug interactions through P450 interactions
advantage of azithromycin
not a substrate of CYP3A4 ○ lowers risk of drug interactions ○ less risk of hepatotoxicity - reduced risk of cardiotoxicity - longer half-life - ability to reduce inflammation, changes gene expression in anti-inflammatory way
Clindamycin
MOA: binds to 50S subunit, inhibits protein synthesis at tRNA binding site bacteriostatic cross resistance with macrolides narrow spectrum (for anaerobic) accumulates in bone penetrates will into abscesses
Chloramphenicol
first successful treatment for typhoid fever
broad spectrum
Streptogramins
MOA: type A: ribosomal initiation complexes assembled normally but functionally inactive. type B: inhibit first two of three elongation steps, do not affect 3rd step
Gram + (MRSA)
excretion: biliary/fecal
Linezolid
MOA: binds in the A site pocket at the peptidyltransferase center of the ribosome overlapping the aminoacyl moiety of an A-site bound tRNA preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis
Gram +
advantages of linezolid
oral preparation with 100% bioavailability (without regard to food)
extensive volume of distribution
100% serum concentrations in lung, bronchi
neither substrate nor inhibitor of CYPs
activity against most gram + bacteria and mycobacteria
drug interactions with linezolid
with SSRIs –> serotonin syndrome
Tetracyclines
MOA: binding reversibly to receptors of the 30S ribosomal subunit, prevent addition of new AA to peptide chain
broad spectrum
bacteriostatic
side effects of tetracyclines
nausea on empty stomach
doxycyline
longer acting tetracycline
95% absorbed, even with food
fecal excretion
adverse effects of tetracyclines
brown discoloration of teeth
photosensitivity
Fanconi-like syndrome from expired
Tigecycline
MOA: similar to tetracycline but avoid efflux pumps
overcomes 2 major mechanisms of tetracycline resistance: efflux pump acquisition and ribosomal protection
advantages of tigecycline
○ Extremely broad range (activity against drug resistant strains and vancomycin-resistant bacteria and mycobacteria)
○ Long half-life (100 mg initial dose followed by 50 mg injection every 12 hours).
○ Resistance is less likely.
Good safety profile.
Aminoglycosides
MOA: enter susceptible bacteria by oxygen-dependent active transport (not anaerobes) and passive diffusion.
Bind to 30s subunit of 70s ribosome. enable binding of incorrect tRNAs
Gram – , aerobic
some Gram +, mycobacteria, mycoplasma, spirochetes
synergize with b-lactams and vancomycin
excretion: renal
high accumulation in kidneys
Adverse effects of aminoglycosides
toxicities in kidneys and auditory system
nephrotoxicity - reversible
ototoxicity - irreversible
Amikacin
aminoglycoside
use against Mycobacterium tuberculosis strains that are multi drug resistant
IM or IV
renally cleared
Neomycin
aminoglycoside
used orally for bowel prep
in topicals
Mupirocin
MOA: bind reversibly to isoleucyl tRNA synthetase. prevents incorporation of isoleucine into growing protein chains. arrests protein synthesis. Gram + cocci topical eliminated S. aureus i nose not effective systemically
