antibacterials Flashcards
folic acid synthesis and reduction
DNA methylation,
PABA inhibitors: sulfonamides,
DHF inhibitor: trimethoprim
peptidoglycan synthesis inhibitors
glycopeptides ( vancomycin, bacitracin)
peptidoglycan x-link inhibitors
pencillinase-sensitive, pencillinase-resistant, antipseudomonals, cephalosporin (I-V), Carbapenems, Monobactams
Pencillinase sensitive
pencillin G,V; ampicillin; amoxicillin
penicillinase resistant
oxacillin, nafacillin, dicloxacillin
antipseudomonals
ticarcillin, pipercillin
cephalosporin I
cefazolin
cephalosporin II
cefoxitin
cephalosporin III
ceftriaxone
cephalosporin IV
cefepime
cephalosporin V
ceftaroline
Carbapenems
imipenem, meripenem, ertapenem, doripenem,
monobactam
aztreonam
DNA integrity inhibitor (via free radicals)
metronidazole
mRNA synthesis inhibitor (via RNA polymerase)
rifampin
DNA gyrase inhibitor
FQN, quinolone
FQN
ciprofloxacin, levofloxacin
quinolone
nalidixic acid
50s protein synthesis inhibitors
chloramphenicol, clindamycin, linezolid, macrolides, streptogramins
macrolides
azmycin, cymcin, emycin
streptogramins
quinupristin, dalfopristin
30s subunit inhibitors
aminoglycosides, tetracyclines
aminoglycosides
gentamicin, neomycin, amikacin, tobramycin, streptomycin
PCN G/V mechanism
D-ala-D-ala structural analog. Binds PBP.
blocks PBP xlink of peptidoglycan in cell wall.
activates autolytic enzymes
PCN G/V use
G+ organisms, syphilis and gonorrhea
bacteriocidal
PCN G/V ADR
hypersensitivity rxns, direct Coombs + hemolytic anemia
PCN G/V resistance
pencillinase in bacteria cleaves b-lactam ring
penicillinase-resistant PCN MOA
same as PCN; narrow spectrum
pencillinase resistant b/c bulky R group blocks access of B-lactamases
penicillinase-resistant PCN use
MSSA
penicillinase-resistant PCN ADR
hypersensitivity rxns, interstitial nephritis
penicillinase-sensitive PCN MOA
same as PCN, wider spectrum
pencillinase sensitive. also combine with clavulanic acid to protect against destruction by b-lactamase
penicillinase-sensitive PCN use
extended-spectrum pencillin
H. influenzae, H pylori, E. coli, listeria monocytogenes, Proteus mirabilis, salmonella, shigella, enterococci
“Ampicillin/amoxicillin HHELPSS kill enterococci”
penicillinase-sensitive PCN ADR
pseudomembranous colitis, rash, hypersensitivity rxns
penicillinase-sensitive PCN mechanism of resistance
penicillinase in bacteria cleaves b-lactam ring
antipseudomonal PCN MOA
same as pcn, extended specturm
antipseudomonal PCN ADR
pseudomonas, gram - rods
antipseudomonal PCN codrug
susceptible to penicillinase. need B-lactamase inhibitors
antipseudomonal PCN ADR
hypersensitivity rxns
B-lactamase inhibitors
clavulanic acid, sulbactam, tazobactam
cephalosporin MOA
b-lactam drugs that inhibit cell wall synthesis, but are less susceptible to penicillinase
bactericidal
organisms not covered by 1-4 generation
(“Lame”)
Listeria, Atypicals (chlamydia, mycoplasma), MRSA, and Enterococci
1st generation cephalosporin use
cefazolin, cephalexin
gram + cocci; PEK
Cefazolin surgical use
prophylaxis to prevent S aureus wound infections
2nd generation cephalosporin use
cefaclor, cefoxitin, cefuroxime (“Fake fox fur”)
gram + cocci; HENS PEK
HENS
H influenzae, Enterobacter aerogenes, Neisseria, Serratia
PEK
proteus mirabilis, E coli, Klebsiella pneumoniae
3rd generation cephalosporin use
ceftriaxone, cefotaxime, ceftazidime
serious gram - infections resistant to other B-lactams
Ceftriaxone use
meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime use
pseudomonas
4th generation cephalosporin use
cefepime
gram - organisms, inc activity against Pseudomonas and gram + organisms
5th generation cephalosporin use
ceftaroline
broad +/- coverage, including MRSA; no pseudomonas
cephalosporin ADR
hypersensitivity rxns, autoimmune hemolytic anemia, disulfiram-like rxn, vitamin K deficiency.
cephalosporin drug interactions
exhibit x-rxn with PCN
inc nephrotoxicity with aminoglycosides
cephalosporins mechanism of resistance
structural changes in PBP
Imipenem (carbapenems) MOA
broad-spectrum, B-lactamase-resistant.
always administered with cilastatin to decrease inactivation of drug in renal tubules
imipenem use
G+ cocci, G - rods, and anaerobes.
wide spectrum, but significant ADR limit use
meropenem
dec risk of seizures and is stable to dehydropeptidase I
carbapenem adr
GI distress, skin rash, seizures at high plasma levels
monobactams MOA
prevents peptidoglycan x-linking by binding to PBP 3. synergistic w/ aminoglycosides.
no cross allergenicity w/ PCN
monobactam use
G- only
used in PCN allergic pts, and those with renal insufficiency
vancomycin MOA
inhibits cell wall peptidoglycan formation by binding to D-ala-D-ala precursor.
Bacteriocidal (except C. Diff –> bacteriostatic)
vanc use
gram + only
vanc ADR
red man sx; nephrotoxicity, ototoxicity, thrombophlebitis
vanc resistance
bacteria change walls to d-ala-d-lac
protein synthesis inhibitors
specifically target smaller bacterial ribosome (70s, made of 30s and 50s), leaving human ribosomes unaffected
30s inhibitors
aminoglycosides (bactericidal); tetracyclines (bacteriostatic)
50s inhibitors
Chloramphenicol, Clindamycin (bacteriostatic)
Erythromycin (bacteriostatic)
Linezolid (variable)
protein synthesis inhibitors mnemonic
Buy AT 30, CCEL at 50
aminoglycosides MOA
bactericidal;
irrev. inhibition of initiation complex thru binding of 30s subunit.
Can cause misreading of mRNA; block translocation.
Require O2 for uptake–>INACTIVE AGAINST ANAEROBES
aminoglycosides use
severe G- rod infections. synergistic w/ b-lactam abx
neomycin
prophylaxis for bowel surgery
aminoglycoside ADR
nephrotoxicity, neuromuscular blockade, ototoxicity
teratogen
aminoglycoside method of resistance
bacterial transferase enzymes inactivate drug by acetylation, phosphorylation, or adenylation
tetracyclines
(bacteriostatic) bind 30s and prevent attachment of aminoacyl-tRNA;
limited CNS penetration
Doxycycline pts
can be used in pts with renal failure due to fecal elimination
Tetracycline drug interactions
milk, antacids, iron preparations b/c divalent cations inhibit drugs absorption in drugs
tetracycline use
Borrelia burgdorferi, M pneumoniae
accumulates intracellularly –> Rickettsia, Chlamydia
acne tx
tetracycline ADR
discoloration of teeth and inhibition of bone growth in children
photosensitivity
contraindicated in pregnancy
Chloramphenicol MOA
blocks peptidyltransferase at 50s (bacteriostatic)
Chloramphenicol use
Meningitis, Rocky mounted spotted fever
chloramphenicol ADR
anemia, aplastic anemia, *gray baby syndrome
gray baby sx cause
premie infants bc lack liver UDP-glucuronyl transferase
Chloramphenicol mech. of resistance
plasmid-encoded acetyltransferase inactivates drug
Clindamycin MOA
blocks peptide transfer (translocation) at 50s (bacteriostatic)
Clindamycin use
anaerobic infections (aspiration pneumonia, lung abscesses, oral infections)
invasive GAS infection
Clindamycin versus metronidazole
clindamycin treats ABOVE diaphragm
metronidazole BELOW diaphragm
Clindamycin ADR
pseudomembranous colitis, fever, diarrhea
Linezolid MOA
inhibit protein synthesis by binding 50s and preventing formation of initiation complex
Linezolid use
G+ including MRSA and VRE
Linezolid ADR
bone marrow suppression (thrombocytopenia); peripheral neuropathy; serotonin syndrome
linezolid mech of resistance
pt mutation of ribosomal RNA
macrolides MOA
inhibit protein synthesis by blocking translocation; bind to 23s rRNA of 50s (bacteriostatic)
macrolides use
atypical pneumonia (Mycoplasma, Chlamydia, Legionella), STIs (chlamydia), gram + cocci, B pertussis
Macrolides ADR
GI motility issue; arrhythmia (prolonged QT interval); acute cholestatic hepatitis; rash; eosinophilia
Macrolides drug interactions
increases serum concentration of theophylline, oral anticoag.
Clarithromycin and emycin inhibit cyp450
Macrolides mechanism of resistance
methylation of 23S rRNA-binding site prevents binding of drug
Sulfonamides MOA
inhibit dihydropteroate synthesis, thus inhibiting folate synthesis (bacteriostatic)
when does sulfonamide become bacteriocidal?
combined with trimethoprim
sulfonamide use
G+/-, nocardia, chlamydia
SMX use
simple UTI
Sulfonamide mech of resistance
altered enzyme (bacterial dihydropteroate synthase), dec uptake, inc PABA synthesis
Dapsone MOA
similar to sulfonamides, but structurally distinct agent
Dapsone use
leprosy, pneumocystis jirovecii prophylaxis
Dapsone ADR
hemolysis if G6PD deficient
Trimethoprim MOA
inhibits bacterial dihydrofolate reductase (bacteriostatic)
Trimethoprim use
used in combo with SMX, causing sequential block of folate synthesis
combo tx: UTI, shigella, salmonella, pneumocystis tx and prophylaxis, toxo prophylaxis
trimethoprim ADR
megaloblastic anemia, leukopenia, granulocytopenia
FQN MOA
inhibit prokaryotic enzymes Topoisomerase II (dna gyrase) and topoisomerase IV. (bacteriocidal)
FQN drug interaction
CANT use antacids
FQN use
G - rods of urinary and GI tracts, Neisseria, some + positive organisms
FQN ADR
contraindicated in pregnant women, nursing mothers, and kids under18 for cartilage damage
tendonitis in 60+ and in pts taking pred
FQN mechanism of resistance
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Daptomycin MOA
lipopeptide that disrupts cell membrane of gram + cocci
daptomycin use
MRSA skin infections, bacteremiam endocarditis, VRE
Daptomycin cant be used in what dx?
pneumonia, inactivated by surfactant
Daptomycin ADR
myopathy, rhabdomyolysis
Metronidazole use
forms toxic free radical metabolites in the bacterial cell that damage DNA. (bactericidal, antiprotozoal)
Metronidazole use
Tx Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, anaerobes (Bacteroides, C diff).
Used with PPI and clarithromycin for triple therapy against H pylori
Metronidazole ADR
disulfiram-like rxn (severe flushing, tachycardia, hypotension)
HA, metallic taste