Week 4 Drugs Flashcards
Rifampin
Binds RNA pol at the active center, blocking elongation of mRNA.
Bactericidal
Spectrum- Mycobacteria tuberculosis, extended
Resistance (intrinsic)- drug is unable to bind to the B subunit of RNA pol, (acquired)- strain aquires mutations in rpoB gene preventing drug binding
Side effects- orange body fluids, could cause faster metabolism of other medication patient is on
Fidaxomicin
inhibits RNA polymerase
Bactericidal
Narrow spectrum- gram + anaerobes (expecially C. diff) spares many gut flora
Adverse effects- few due to low absorption
Resistance- point mutation in RNA pol has been observed in vitro
Fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin- Inhibitors of DNA replication by binding bacterial DNA topoisomerase II (gyrase) & IV. Cause double stranded breaks which lead to cell death
Bactericidal
BROAD SPECTRUM (+,-, and aytpical mycolplasma pneumonia and UTI)
Resistance- overperscribed, efflux, mutations in topoiomerases
Sulfonamides
folate antagonist, indirect inhibition of DNA synthesis. Drug is PABA analog and is competitive inhibitor.
Bacteriostatic
Trimethoprim
indirect inhibition of DNA synthesis, inhibits DHFR (low affinity for mammalian one)
Bactrin
Sulfonamide + Trimethoprim = double blockade, bacteriocidal
Metronidazole (Tinidazole)
When it is reduced it generates free radicals leading to DNA strand breaks and cell death (it is only metaolized to active form in ANAEROBES)
Spectrum- anaerobic bacteria including C. diff and protozoa
Resistance is rare
Adverse effects- disulfiram-like reaction with alcohol
Disulfiram reaction
due to increased serum acetaldehyde. Metronidazole blocks aldehyde dehydrogenase, inhibiting oxidation of acetaldehyde and causing marked increase in acetaldehyde concentrations after ethanol consumption → very bad hangover (throbbing headache, nausea, vomiting, sweating, hypotension, confusion
Nitrofurantoin
indirect inhibitor of DNA
Reduced to reactive intermediates, inactivate or alter bacterial ribosomal proteins to inhibit the synthesis of DNA, RNA< cell wall and protein
BROAD SPECTRUM
Lack of resistance
Identify most likely agent associated with urinary tract infections and factors influencing diagnosis and treatment
- E. Coli is the agent most associated with UTIs
- Part of normal GI flora, but becomes pathogenic when transferred to urinary tract, acquires toxins, or is able to overgrow
- Use serotyping to identify pathogenic strains
- Many enterobacteriaceae have acquired plasmids for extended spectrum B-lactamases
- Resistance patterns to TMP-SMX (bactrin) and fluoroquinolones are variable
- Nitrofurnatoin is preferred in these cases
Linezolid
Bacteriostatic
Inhibits protein synthesis by binding to the 23S rRNA in the 50S subunit
Prevents initiaiton
Gram + including MRSA and VRE
Resistance- alterations in 23S ribosomal RNA
Adverse effects- Bone marrow suppression, Serotonin Syndrome
Aminoglycosides
(Gentamicin, amikacin, tobramycin, neomycin, streptomycin)
Bactericidal- prevents formation of initiation complex, misreading of mRNA and induces early termination
Gram neg aerobic
Resistance- failure to enter cell (anaerobic) so treat with cell all inhibitor, inactivation enzyme
**Limited use because of side effects, nephrotoxicity, ototoxicity (vestibular and auditory dysfunction)
gentamicin
Aminoglycoside
amikacin
Aminoglycoside
tobramycin
Aminoglycoside
streptomycin
Aminoglycoside
neomycin
Aminoglycoside
Tetracyclines
Bacteriostatic
Bind 30 S preventing attachment of aminoacyl-tRNA
Broad spectrum initially but now B. burgdorferi (LYMES), H. pylori, Mycoplasma pneumoniase
Resistance- increased efflux, decreased uptake, alteration of target
Adverse effects- chelates with metal ions decrease gut abosorbtion
doxycycline
tetracylcine
demeclocycline
tetracycline
minocycline
tetracylcine
Chloramphenicol
bacteriostatic
binds 50S preventing peptide bond formation- peptidyltransferase can’t associate with amino acid substrate
Extended spectrum- but use is limited because of side effects
Resistance- acetyltransferase modifies it to prevent binding
Toxic, bone marrow depression, aplastic anemia, grey baby syndrome (cuz they have decreased renal function)
Macrolides
erthromycin, azithromycin, clarithromycin
bacteriostatic
inhibits translocation by binding 23S rRNA of the 50S subunit
Spectrum- broad coverage of respiratory pathogens, Chalmydia
Resistance- methylation of 23S rRNA binding site, efflux, hydrolysis by esterases
Adverse effects- haptic failure, inhibitors of cyto p450 enzymes
erythromycin
macrolide
azithromycin
macrolide
clarithromycin
macrolide
Drugs effective against Mycoplasma pneumonia
Doxycyclin, azithromycin, levofloxacin
**B-lactams are not effective
Clindamycin
bacteriostatic
blocks translocation at 50S ribosomal subunit
Gram +, treat acne
Resistance- mutation of ribosome, methylation of rRNA, cross resistance with macrolides and streptogramins, inactivation of drug by adenylation
Adverse effects- hypersensitivity, superinfection with C. diff
Streptogramins
Quinupristin/ Dalfopristin
Combined action is bactericidal for some organisms, binds 50S to inhibit translocation
**should be reserved for infection caused by multiple drug resistance Gram + ***
Adverse Effects- arthralgias and myalgias, inhibits ctyo P450, significant drug interactions
Quinupristin
streptogramin
Dalfopristin
streptogramin
Ciprofloxacin
fluoroquinolone
levofloxacin
flurorquinolone
moxifloxacin
fluoroquinolone
Mechanism of Resistance- Decreased uptake
Tetracycline, sulfonamides, aminoglycosides, chloramphenicl
Mechanism of Resistance- Efflux
Cephalosporins, aztreonam, tetracyclines, macrolides, streptogramins, fluoroquinolones, sulfonamides
Mechanism of resistance- altered target
b-lactams, vancomycin, rifampin, fluoroquinolones, sulfonamides, trimethoprim, linezolid, streptogramins, tetracyclins, erythromycin, clindamycin
Mechanism of resistance- up-regulation of substrate
sulfonamides- increased levels of PABA synthesis
Mechanism of resistance- enzymatic alteration of antibiotic
penicllins, cephalosporins (B-lactamases)
Aminoglycosides (acetyl group)
Chloramphenicol (acetlytransferase action)
Tetracyclines (minor acetylation)
Macrolides (esterases)
Clindammycin (adenylation)
metronidazole (decreased drug activation)
Drugs reserved for infections like MRSA and VRE
5th ge cephalosporin, vancomycin, daptomycin, quinupristin-dalfopristin, linezolid
