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187 Cards in this Set
- Front
- Back
where does stage 1 occur
|
cytoplasm
|
|
what drugs work at stage 1 of bacterial cell wall synthesis
|
"F DC"
fosfamycin D-cycloserine |
|
where does stage 2 occur
|
cytoplasm --> outer leaf of cell membrane
|
|
what drugs work at stage 2 of bacterial cell wall synthesis
|
"VBT"
vancomycin, bacitracin, teichoplanin (same as vanco) |
|
where does stage 3 of bacterial cell wall synthesis occur
|
cell wall
|
|
what drugs work at stage 3 of bacterial cell wall synthesis
|
beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactam)
|
|
what bacteria are resistant to the antibiotics that inhibit cell wall synthesis? what are these antibiotics?
|
atypical bacteria (mycobacteria, chlamydia, legionella) DON'T have peptidoglycan in cell wall so resistant to fosfomycin/D-cycloserine (stage 1), vanco/teichoplanin/ bacitracin (stage 2) and B-lactam antibiotics(stage 3)
|
|
sequence of stage 1 of bacterial cell wall synthesis
|
1. UTP + NAG = UDP-NAG +PPi
UTP and NAG each lose 1Pi to bond 2. UDP-NAG + lactoyl = UDP-NAM T-shaped molecule is the final product of stage 1 |
|
fosfomycin
|
inhibits addition of lactoyl group to UDP-NAG thus inhibits formation of UDP-NAM
single 3g dose for uncomplicated UTIs; alternative for Bactrim DS (sulfa-trim); safe for pregnancy |
|
D-cycloserine
-MOA -reversibly inhibits___ -irreversibly inhibits___ |
cyclic analog of D-Alanine
1. blocks enzymes required to synthesize D-Ala-D-Ala dipeptide 2. can't make NAM pentapetide *reversible (competitive) inhibition of D-Ala-D-Ala synthetase *irreversible inhibition of D-Ala racemase of the host --> potential toxicity! |
|
sequence of stage 2 of bacterial cell wall synthesis
|
1. transport of NAM-pentapeptide (bound to lipid transporter via diphosphate bond) from cytoplasm to exterior leaf of cytoplasmic membrane
2. add NAG to NAG-NAM-pentapeptide-diphosphate transporter 3. 5-Gly added to Lys (3rd AA in pentapeptide sidechain); last Gly has free NH2 group 4. NAG-NAM-peptide brick incorporated into unfinished PG cell wall 5. diphosphate linkage broken and both Pi's remain with transporter 6. transporter recycled by cleavage of one of the Pi's |
|
bacitracin MOA (and stage)
|
-works in stage 2 of bacterial cell wall synthesis
-inhibits recycling of transporter by preventing cleavage of one of the Pi's |
|
vancomycin MOA
|
recognizes and sits on D-Ala-D-Ala so that the "brick" can't fit into cell wall acceptor molecule
|
|
what must be present for vancomycin to work
|
D-Ala-D-Ala terminal group
|
|
how is vancomycin resistance developed
|
bacteria replace D-Ala-D-Ala with D-Ala-D-lactate, so vancomycin doesn't recognize mutation
VRE (vancomycin-resistant enterococci) use this mechanism |
|
vancomycin administration
-IV for ___ -PO for ___ (try ____ first to prevent vanco resistance) -for ____ infections try ____ first |
-IV for everything
-PO for pseudomembranous colitis (C.difficile), but use metronidazole first to prevent vancomycin resistance for enterococcal infections, try ampicillin first |
|
vancomycin coverage & DOC
|
serious G+ only!!!
no G- coverage *DOC for MRSA/MRSE (with rifampin and/or gentamicin) *DOC for ampicillin-resistant enterococcus (with gentamicin) |
|
vancomycin side effects/toxicities
|
RON
1. Red-man syndrome from histamine displacement 2. Ototoxicity (irreversible) 3. Nephrotoxicity (reversible) Oto/nephrotoxicity more common when combined with aminoglycoside (neomycin/gentamicin) --> measure trough level to prevent ototoxicity |
|
teichoplanin
|
same MOA & spectrum as vancomycin
|
|
bacitracin MOA
|
G+ ONLY
inhibits cell wall formation by preventing recycling of phospholipid carrier --> inhibition of Pi cleavage |
|
bacitracin administration
|
topical only due to nephrotoxicity
|
|
polymyxin MOA
|
G- ONLY
cationic detergent that disrupts bacterial cell membrane --> no effect on cell wall synthesis |
|
polymyxin usually administered ____
-used ___ for ___, ___ and ___ |
topically - nephro/ neurotoxicity when used IV
Polymyxin E and Polymyxin B used IV for: -MDR pseudomonas aeruginosa -ancinetobacter -MDR ESBL-producing klebsiella |
|
sequence of stage 3 of bacterial cell wall synthesis
|
1. transpeptidase directs cross-linking of free NH2 of terminal Gly in one chain to the next-to-last D-Ala in nearby side chain
2. terminal D-Ala is kicked out during the cross-linking process 3. 3-D cross-linked structure is very stable |
|
natural penicillins (2)
|
penicillin G
penicillin V |
|
penG DOC for... (7)
hint: "PeniCilliNSS" |
-Peptococcus/Peptostreptococcus
-C. tetanus - metronidazole is now DOC, but penG still effective -C. perfringens (clindamycin also) -Neisseria meningitidis -Syphilis -Strep. pneumoniae (low or intermediate resistance strains only) |
|
penG not used for...
|
-UTI - no G- bacilli coverage (B.frag)
-C.diff - become quickly resistant -Staph - most species produce penicillinases (cleave penG/penV) -Gonococci - become quickly resistant |
|
PO choice penicillin
|
penV
|
|
IV/IM choice penicillin
|
penG
|
|
penG:
-1 of the worst for causing ___ -t1/2 |
SEIZURES (imipenem is even worse)
short t1/2 (30 min) --> probenecid competes with renal secretor & prolongs penG's action |
|
penG depot formulations
|
1. procaine penicillin - releases penG slower than Na or K salts
2. benzathine penicillin - given to soldiers before going overseas as single shot for syphilis prophylaxis; mixed with ammonium base, serum levels up to 30 days; also for rheumatic fever prophylaxis (Strep. pyogenes) **dose adjustment in renal failure |
|
penV
|
-added methoxy group to benzene ring of penG
-PO only -potassium salt (penVK) **dose adjustment in renal failure |
|
penG aka
|
benzyl penicillin
|
|
penV aka
|
phenoxymethyl penicillin
|
|
penicillinase-resistant penicillins aka "anti-staph" or "B-lactamase resistant" penicillins
-treat ___ and ____ only -MOA |
CONDoM drugs: cloxacillin, oxacillin, nafcillin, dicloxacillin, methicillin
-staph and G+ ONLY -bulky group at 6-APA nucleus --> too big to fit into penicillinase but still fit into transpeptidase and other PBPs to inactivate them |
|
methicill-IN
|
-prototype drug: 1st penicillinase-resistant penicillin
-DO NOT GIVE PO (INtravenous only) -causes IN: Interstitial Nephritis |
|
nafcillin
-elimination -administration -side effects |
-highest biliary elimination of all penicillins (70% biliary) --> used in renal failure "no need for nephrons with nafcillin"
-can use PO, but IV preferred -highly plasma bound -neutropenia (10%) and increased LFTs -BM suppression at high doses |
|
which B-lactamase-resistant drugs (CONDoM) are PO/IV choice? which one is no longer marketed in US? whats the order of highest-->lowest oral bioavailability?
|
-Cloxacillin: no longer marketed in US
-Oxacillin: IV > PO -Nafcillin: IV > PO -Dicloxacillin: PO > IV -Methicillin: no longer used (toxic) -PO bioavailability: Dicloxacillin > Cloxacillin >Oxacillin (the more chlorines, the more lipophilic) |
|
aminopenicillins (2)
|
AA
ampicillin amoxicillin |
|
aminopenicillins DOC for
hint: LEP |
Listeria
Enterococcus Proteus mirabilis |
|
aminopenicillin coverage
|
SS HEMP +B
Salmonella Shigella Haemophilus influenzae E. coli Morexella catarrhalis (MCAT) Proteus mirabilis (wimpy proteus in UTIs) B.frag (+ must combine with B-lactamase inhibitor) |
|
ampicillin
-take on ___stomach -major side effect -oral bioavailablity -most likely to cause ___ |
-take on EMPTY stomach
-major diarrhea: incomplete/erratic intestinal absorption -low PO F -MOST LIKELY to cause pseudomembranous colitis/superinfection |
|
amoxicillin
-administration |
-more lipophilic = PO choice
-lower concentration in gut when used to treat intestinal infections --> for salmonella/shigella, use ampicillin |
|
anti-pseudomonal penicillins (5)
|
PM CAT: piperacillin, mezlocillin, carbenicillin, azlocillin, ticarcillin
|
|
anti-pseudomonal penicillins used for
|
-mainly serious, nosocomial G- bacilli infections
|
|
uredopenicillins
|
MAP: mezlocillin, azlocillin, piperacillin
-contain urea group -hydrophilic = more affinity for porins of G- outer envelopes |
|
ticarcillin/carbenicillin
-structure -main side effects (2) |
-2 carboxy groups
-watch Na load in CHF patients: drug expands ECF -administered as di-Na salt: expansion of ECF --> dilutional hypokalemia -interferes with platelet aggregation (coagulopathy) |
|
timentin
|
ticarcillin + clauvalanic acid
|
|
carbenicillin prodrug
|
-carbenicillin indanyl sodium
-the only PO formulation amongst PM CAT penicillins |
|
piperacillin
-best of all penicillins against___ and ____ |
pseudominas aeruginosa and B.frag
GREAT for ANAEROBE coverage |
|
zosyn
-covers ___ -DOC for ___ |
-piperacillin+tazobactam (B-lactamase inhibitor)
-covers B.frag -DOC for non-meningital pseudomonas aeruginosa when combined with aminoglycoside for 2x coverage |
|
specific mechanisms of penicillin resistance (2)
|
1. failure to reach PBPs
2. porin-deficient mutation |
|
how does failure to reach PBP confer penicillin resistance
|
-B-lactam antibiotics must pass thru G- envelope via porins to reach target site
-agents unable to pass thru porins can't cross envelope thus ineffective for G- |
|
how does porin-deficient mutation confer penicillin resistance
|
resistance occurs when porin proteins are mutated, or less frequently when synthesis of porins is reduced; either way, penicillins don't get to the PBPs and irreversibly inhibit them, thus they (and other antibiotics that enter thru porins) are useless
|
|
single most important method of penicillin resistance
|
PRODUCTION OF B-LACTAMASE
|
|
what are B-lactamases
|
group of related enzymes elaborated by bacterial cells that are capable of hydrolyzing the B-lactam ring which inactivates antibiotic
|
|
how does acquisition of altered PBPs reduce affinity for B-lactam antibiotics
|
-mutated transpeptidases able to differentiate btw D-Ala and B-lactam, so still able to cross-link
-all B-lactam antibiotics are ineffective -MRSA + MRSE |
|
DOC for MRSA/MRSE
|
vancomycin
-doesn't require transpeptidase to be present & not dependent on PBPs -now seeing VRSA/VRSE |
|
efflux mechanisms
|
-often seen in pseudomonas
-increased expression of P-GP (p-glycoprotein) efflux pump |
|
treatment of low-resistance strep. pneumoniae
|
normal penG dose
|
|
treatment of medium-resistance step. pneumoniae
|
higher dose penG
|
|
treatment of high-resistance step. pneumoniae
|
-vancomycin + ceftriaxone
-levofloxacin/moxifloxacin are alternatives |
|
adverse reactions of penicillins
|
SNL BB SIN
Sensitivity reactions Neutropenia Leukopenia Bone marrow suppression Bleeding Seizures Interstitial nephritis Na+ overload/hypokalemia |
|
penicillin-induced sensitivity reactions
|
-skin rashes: macropapular w/itch (most likely from ampicillin)
-acute anaphylaxis: 10% mortality (most likely from penG) -benzylpenicilloyl hapten: covalently links to lysines of body proteins, accounts for 95% of tissue-bound penicillin, major determinant of hypersensitivity |
|
if allergic to 1 penicillin...
|
...allergic to ALL penicillins
|
|
penicillin-induced leukopenia
|
decreased WBC; rarely seen with all penicillins
|
|
penicillin-induced neutropenia most likely with ____
|
nafcillin (N/N)
|
|
penicillin-induced prolonged bleeding time most likely with ___ and ___
|
ticarcillin and carbenicillin
|
|
which antibiotics cause penicillin-induced Na+ overload/hypokalemia
hint: anti-pseudomonal penicillins (2) |
-ticarcillin and carbenicillin
-caution in CHF/renal failure |
|
penicillin-induced seizures
|
most likely penG
|
|
penicillin-induced interstitial nephritis
|
most likely methicillin
|
|
penicillin-induced BM suppression most likely caused by___
|
IV nafcillin
reversible |
|
cephalosporins
-MOA -NOT cleaved by ___ -CAN give to pts allergic to ____ |
-same MOA as penicillins: inhibit transpeptidase from cross-linking cell wall
-NOT cleaved by penicillinases -give to pts allergic to CONDoM drugs |
|
cephalosporinases
|
-1st generation more likely to be cleaved
-drugs become more resistant to cephalosporinases with increasing generation (4>3>2>1) |
|
ESBL
-found on ___ -cleave ___ and ___ with ___ group -carried by ___ and ___ organisms |
-extended spectrum B-lactamase, found on plasmids
-cleave several important 3rd gen ceph's + aztreonam (monobactam) with oxyimino group --> important bc these drugs are considered gold standard against serious G- infections -klebsiella + E. coli carry ESBL |
|
Amp-C B-lactamase action on cephalosporins
|
-Amp-C are chromosomal cephalosporinase elaborated by G-
-3rd generation ineffective against Amp-C -4th generation (cefepime) relatively stable to Amp-C |
|
CASE organisms + DOC for their treatment
|
Citrobacter freundii: Amp-C
Acinetobacter: no Amp-C Serratia marcesans: Amp-C Enterobacter cloacae: AmpC DOC: carbapenems |
|
which cephalosporin effective against enterococcus sp. (G+)
|
NONE!!!
|
|
which cephalosporin effective against MRSA/MRSE
|
NONE!!!
|
|
2nd generation cephamycins stable to ___ &___ but not___or____
|
stable to mild cephalosporinases and ESBL, but not to Amp-C or metallo-B-lactamases
|
|
oral 1st generation cephalosporins (3)
|
"Rad Alex Rox PO"
-cephRADine -cephALEXin" -cefadROXil |
|
3rd gen ceph's with biliary excretion
|
sounds like "pair of tricks"
-cefoperazone -ceftriaxone |
|
1st gen ceph's that cross BBB = 1st line for meningitis
|
TRI-TAX-EPI-RAZ
-cefTRIaxone -cefTAXime -cefEPIme -ceftRAZidime |
|
DO NOT use this 1st gen ceph for meningitis
|
cefuroxime
|
|
ceph's with MTT (methylthiotetrazole) side chain
|
"i MET a TAN MAN in the endZONE"
-cefMETazole (2nd gen cephamycin) -cefoteTAN (2nd gen cephamycin) -cefMANdole (2nd gen ceph) -cefoperaZONE (3rd gen ceph) causes: 1. bleeding - inhibits conversion of prothrombin to thrombin; co-admin vitamin K 2. disulfuram-like reactions with EtOH |
|
1st gen ceph's adverse effects
|
"BB King SUPER-SENSITIVE to DISses"
-Bleeding (worst with moxalactam - discontinuted) -Biliary sludging (ceftriaxone only) -Kernicterus (ceftriaxone & sulfonamides) -SUPERinfection -hyperSENSITIVITY reactions -DISulfuram-like reaction with EtOH |
|
1st gen ceph's USes
|
USSS - UTI, Skin, Soft tissue, Surgical prophylaxis
|
|
cefazolin
-__gen ceph -administration -used againST ___ and ___ -enters ____ |
-1st gen
-IV extensive use againST STaph auerus/epidermitis and STrep pyogenes -used during orthopedic surgery because ENTERS BONE |
|
2nd gen ceph's
-uses -coverage |
Use: respiratory disorders + UTI; rarely 1st line
Coverage: -G+ (just a little less than 1st gen) -G- "Please Enter the National Institute of Mental Health" Proteus mirabilis E.coli Neisseria gonorrhea Indole + proteus MCAT H.flu |
|
cefaclor frequent side effect
hint: side effects make you "sick" |
serum sickness
|
|
cefuroxime axetil
|
-PO PROdrug
-the ONLY 1st/2nd PO gen ceph that crosses BBB -good for comm-aq. pneumonia (CAP) -DOC for MCAT -cefuroxime+metronidazole = alternative to cefoxitin for abdominal surgery prophylaxis & "dirty surgery" |
|
cefPOdoxime
|
-3rd gen ceph
-PO -tx gonorrhea |
|
cefPrOzil
|
-PO
-tx CART (community-acquired respiratory tract) infections |
|
loracarbef
|
"carbacephem"
not used very often |
|
cephamycins
|
-subtype of 2nd gen ceph's
-more B-lactamase stable than 1st, 2nd and 3rd gen ceph's -stable vs. ESBL -same G+ & G- coverage as cephalosporins, but also cover difficult anaerobes (B.frag) --> no longer reliable "METAL TAN FOX" cephMETAzone cefoteTAN ceFOXitin |
|
cefmetazole
|
seldom used bc of MTT side chain --> bleeding & disulfuram-like rxn with EtOH
|
|
cefotetan
hint: has 2 t's... |
2nd longest t1/2 of all ceph's (ceftriaxone is #1) --> BID dosing
|
|
cefoxitin
|
-no longer considered reliable against B.frag; still used but for prophylaxis of abdominal surgery
|
|
new DOC for severe peritonitis (appendicitis/diverticulitis) (6)
|
-carbapenems
-piperacillin + tazobactam -tigecycline -metronidazole + ceftriaxone (3rd gen) -metronidazole + quinolone -ampicillin + sulbactam |
|
3rd gen ceph's uses
|
-DOC for serious nosocomial G- especially with enterobacteriaceae
-Neisseria meningitidis -respiratory infections & sepsis (lung origin) -penetrate better into eye & CNS |
|
3rd gen ceph's
-excellent coverage of ____ and ____ -empirical treatment of ____ and ____ -less effective than 1st/2nd gen for ____ |
-strep pneumoniae and enterobacteriaceae (salmonella, E.coli, indole+ proteus)
-empirical tx of CAP (community-acquired pneumonia) and meningitis -less effective for staph than 1st/2nd gen |
|
ceph's that tx meningitis (cross BBB)
|
"FURious OX and TAZ TRIed EPI in a TAXI"
-ceFUROXime -cefTAZidime -cefTRIaxone -cefEPIme -cefoTAXIme |
|
what 3rd gen ceph's are active against weaker anaerobes (2)
|
"my country TIZ of me, that's why it TAXes me"
-Cefotaxime -Ceftizoxime *not clinically significant --> not 1st/2nd line tx for any anaerobe |
|
3rd gen ceph that covers B.frag
hint: "tiz fragile" |
ceftizoxime
|
|
ceftriaxone
-dosing -price -t1/2 -coverage |
-superstar!!!
-generic and QD dosing -longest t1/2 of all ceph's -covers wimpy G+ anaerobes but not DOC |
|
ceftriaxone is DOC for ____ & _____
|
Neisseria gonorrhea & penicillin-resistant strep pneumoniae (+ vanco for G+)
|
|
ceftriaxone excretion
|
60% biliary, 40% urinary
in renal/liver failure, elimination will switch over to healthy organ |
|
ceftriaxone common side effect
|
biliary sludging
|
|
cefotaxime is alternative to ____ for ______
-covers ___ -lacks ___ |
-alternative to ceftriaxone for penicillin-resistant strep pneumoniae
-covers wimpy G+ anaerobes but not DOC -no biliary sludging (unlike ceftriaxone) |
|
cefoperaZONE
-treats____ but NOT____ (caused by same bug)...BBB -excretion -structure |
-pseudomonas aeruginosa but NOT pseudomonal meningitis (doesn't cross BBB)
-"the nafcillin of the cephalosporins" --> biliary excretion (80%) -MTT side chain = limits use (bleeding + disulfuram rxn) |
|
ceftazidime
-effective against___ -DOC for___ -susceptible to ___ |
-pseudomonas aeruginosa
-X BBB --> DOC for pseudomonal meningitis -easiest ceph to be cleaved by ESBL |
|
peripheral pseudomonas aeruginosa tx (non-meningital)
|
always 2x coverage!!!
-piperacillin/tazobactam (zosyn) + aminoglycoside |
|
ESBL-producing pseudomonas aeruginosa tx
|
-cefepime (4th gen) X BBB & resistant to ESBL
|
|
the 3 MOST IMPORTANT 3rd gen parenteral ceph's
|
"T's"
-cefTriaxone -cefoTaxime -cefTaxidime |
|
4th gen ceph coverage
|
-CEFEPIME = the only 4th gen ceph
-excellent G- coverage -good G+ coverage -used when 3rd gen ceph's don't work -NOT good for anaerobes (B.frag) -use for bugs that display MDR (multidrug resistance) |
|
cefepime is MORE stable against B-lactamases of ___ organisms (____and ____)
|
G-
Amp-C (CS+E of CASE organisms) and ESBL |
|
cefepime gets thru ____ because its a _____
|
porins of G- envelopes
zwitterion |
|
cefepime is DOC for ____ because it crosses ____ and is resistant to ___
|
pseudomonal meningitis
BBB ESBL |
|
cefepime administration
|
BID, parenteral only
|
|
carbapenems (3) & their coverage
|
"IME" imipenem, meropenem, ertapenem
-broadest spectrum of any B-lactam antibiotics -VERY stable against ESBL, Amp-C, penicillinase, cephalosporinase -NO coverage of MRSA, atypicals (mycobacterium, chlamydia, legionella), or metallo-B-lactamases |
|
imipenem coverage
|
"gorilla-cillin"
-G+, G-, anaerobes, B.frag, pseudomonas aeruginosa (but NOT pseudomonal sp), enterococcus faecalis (but NOT enterococcus faecium) |
|
imipenem DOC for...
hint: IMIP = IMakeIncrediblePastries |
"CAKES" = CASE organisms + klebsiella
-Citrobacter (Amp-C) -Acinetobacter -Klebsiella (ESBL producing) -Enterobacter (Amp-C) -Serratia (Amp-C) |
|
imipenem is cleaved by____
|
metallo-B-lactamases
bright side: very rare :o) |
|
imipenem administration
|
IV only + expensive - save for MDR infections, CASE organisms, & empirical therapy for serious infections
|
|
imipenem metabolism
|
-metabolized to nephrotoxic substance by renal dehydropeptidases
-give equal amounts of CILASTATIN (inhibitor of brush border dehydropeptidases) -imipenem+cilastatin= Primaxin |
|
imipenem uses
|
"LUIG-E, MD. - POLYspecialist in BACK and BONE
-Lower resp. -UTI -Intra-abdominal -Gynecological -Endocarditis -MDR organisms -POLYmicrobial -BACterial septicemia -BONE, joint and skin |
|
imipenem adverse effect/cross sensitivity
|
-SEIZURES (higher than with penG)
-more common in renal failure -don't use in children (seizure risk) -cross sensitivity with penicillin allergies |
|
meropenem
|
-NO cilastatin needed
-NO seizures -CAN use in children |
|
ertapenem
|
"monkey-cillin"
-NO activity against "APE" --> Acinetobacter, Pseudomonas, Enterococcus sp -NO cilastatin needed -use for MDR E.coli, pyelonephritis |
|
monobactam
|
aztreonam
|
|
aztreonam MOA
|
-irreversibly inhibits PBP-3 which forms septum during bacterial division
|
|
aztreonam coverage
|
- G- aerobes (pseudomonas aeruginosa)
-B-lactamases, Amp-C, metallo-B-lactamases -NOT G+ anaerobes -NOT ESBL (chemical structure has oxyimino moiety) |
|
aztREonam excretion
|
-renal (majority)
-NO dose adjustment needed for renal failure :o) |
|
aztreonam cross-sensitivity
|
-very rare!
-CAN use with penicillin allergies -LEAST cross-sensitivity amongst all B-lactam antibiotics |
|
aztreonam use
|
-reserve for serious G- infections
-lung, bone, UTI, blood |
|
B-lactamase inhibitors
|
-minimal/NO antibacterial activity on their own
-always combined with B-lactam antibiotic |
|
-which B-lactamases are susceptible to B-lactamase inhibitors?
-which B-lactamases are NOT susceptible? |
-penicillinase, cephalosporinase, ESBL
-NOT for Amp-C (use imipenem/meropenem for CSE) -NOT for metallo-B-lactamases |
|
amoxicillin + clavulanic acid
|
augmentin
**the only PO product |
|
ticarcillin + clavulanic acid
not good for ___ |
timentin
kelbsiella |
|
ampicillin + sUlbactam
|
unasyn
|
|
piperacillin + taZObactam
not good for ____ |
zosyn
klebsiella |
|
penicillins DO NOT distribute well into...(5)
|
-eye
-brain/CNS -joint -bone -prostate |
|
which generation ceph's can penetrate CNS
|
3rd and 4th gen CAN X BBB
1st and 2nd gen CAN'T X BBB |
|
what is the major pathway of elimination for most penicillins, cephalosporins, carbapenems and aztreonam
|
RENAL
|
|
what drug is co-administered that competes for serum protein binding sites and increase the amount of FREE antibiotic available to kill bacteria
|
probenecid
|
|
penicillins have ___ half-lives
|
short
dose q3-4h |
|
which antibiotics do NOT require dose adjustment in renal failure (6)
hint: 4 B-lactamase resistant penicillins and 2 3rd gen ceph's |
-COND: cloxacillin, oxacillin, nafcillin, dicloxacillin
-ceftriaxone -cefoperazone |
|
cephalosporins half-life
|
-longer than penicillins
-ceftriaxone = LONGEST **TRIAthalons are LONG |
|
penicillins and cephalosporins are secreted into ___ to some extent
-common side effect -risk for ___ -caution in ___ |
BILE
**diarrhea always present **risk of superinfection **caution in liver failure - drug accumulates and causes toxicity |
|
which antibiotics have biliary excretion component
hint: 3 classes of B-lactamase antibiotics |
-COND: cloxacillin, oxacillin, nafcillin, dicloxacillin
-PM CAT (anti-pseudomonal): piperacillin, mezlocillin, carbenicillin, azlocillin, ticarcillin -cefoperazone -ceftriaxone |
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what are the chances of developing hypersensitivity reaction to a cephalosporin if you are NOT allergic to penicillin
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1-3%
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what are the chances of developing hypersensitivity to cephalosporin if you ARE allergic to penicillin
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7-8%
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what is the initial step in eliciting an immune response to an antibiotic
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formation of antigen
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sequence of events of eliciting an allergic response
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1. internal isomerization within B-lactam antibiotic
2. electrophilic C atom undergoes nucleophilic attack by NH2 (lysine) or SH (cysteine) of body proteins 3. complex forms (hapten-protein conjugate) 4. hapten-proten conjugate triggers formation of antibodies --> allergic response |
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aminopenicillins coverage
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SS HEMP +B
Salmonella Shigella H.flu E.coli MCAT Proteus mirabilis B.frag (G-bacilli: must combine with B-lactamase inhibitor) |
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T/F: aminopenicillins are resistant against B-lactamase
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FALSE!
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aminopenicillins are effective against G- because they're ____ thus able to pass thru ____
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zwitterions
porins of G- envelopes |
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which organisms are susceptible to antipseudomonal penicillins
hint: PIB |
-pseudomonas aeruginosa (with B-lactamase inhibitor + aminoglycoside)
-indole + proteus -B.frag (with B-lactamase inhibitor) |
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which organisms are NOT susceptible to antipseudomonal penicillins
hint: BLacK |
-B-lactamase
-Klebsiella |
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oral penicillins
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-penV
-amoxicillin -ampicillin -dicloxacillin -carbenicillin (indanyl sodium formulation only) |
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G+ B-lactamase production
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-B-lactamases secreted outside the cell into surrounding media
-encoded by plasmids AND chromosomes |
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G- B-lactamase production
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-B-lactamases concentrated in the periplasmic space between envelope and cytoplasmic membrane
-encoded by plasmids OR chromosomes |
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"foxes get dirty"
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ceFOXitin is the DOC for "dirty surgery" - abdominal surgery where potential for mixed infections exists
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1st gen ceph coverage
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-G+
-some G- "PEcK" Proteus mirabilis E.coli Klebsiella |
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2nd gen ceph coverage
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-less G+
-more G- "HEN PEcK" H.flu Enterobacter Neisseria Proteus mirabilis E.coli Klebsiella |
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3 most important things about METal TAN FOX
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cefMETazole, cefoteTAN, ceFOXitin
1. effective against anaerobes, esp. B.frag; DOC for B.frag are metronidazole and clindamycin 2. beta lactamase resistant, more so than penicillins; stable to ESBL but NOT to Amp-C 3. not true cephalosporins, but are cephamycins |
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in what form is an acidic drug found in the body when its pH>pKa
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ionized
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in what form is an acidic drug found in the body when its pH<pKa
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unionized; this is what happened with the original parent sulfanilamide drug because of its low solubility/high pKa
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for every 1 pH unit decrease in the surrounding area of the drug, what happens to the absolute amount of unionized drug
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10X increase in the amount of UNionized drug; the more unionized drug present, the less soluble it is and thus less drug enters the body
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toxic side effect of original sulfanilamide parent drug
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low pH of the urine and high pKa of the drug = [high] of unionized drug = precipitation = crystalluria
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2 ways to prevent crystalluria
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1. "force fluids" - consume large amounts of water/non-EtOH to flush drug out of the kidneys
2. alkalinize urine with NaCO3 to balance amount of - and + charged particles present in urine |
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sulfonamide MOA
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inhibition of dihydropteroate synthetase
para-aminophenyl-sulfonamide moiety resembles PABA --> bacteria can't make thymidylate (T) --> can't make dihydrofolic acid (DHFA) --> bacteriostatic |
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dapsone
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sulfone antibiotic used to treat leporsy
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para-aminosalicylic acid (PAS)
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sulfonamide antibiotic used to treat TB; very similar structure to PABA --> same MOA as sulfonamides
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sulfonamide absorption
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from intestine
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sulfonamide distribution
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-pass into ALL body fluids/tissues
-X BBB |
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sulfonamide metabolism
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-not extensively metabolized
-mainly by acetylation of primary amino group on aromatic ring |
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sulfonamide elimination
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renally
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sulfonamide adverse effects
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CRYSTAL KERN likes wearing HYPERshort HEMlines
-crystalluria -kernicterus (neonates) -hypersensitivity reactions -hematopoietic rxns |
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sulfonamide hypersensitivity reactions
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-Steven-Johnson syndrome
-present on 9th day of tx; consequent exposure causes immediate rxn -more common with long-acting sulfonamides |
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if you're allergic to 1 sulfonamide...
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...you're allergic to ALL of them
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sulfonamide hematopoietic reactions
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-hemolytic anemia in glu-6-phosphate dehydrogenase deficiency (G6PDD)
-agranulocytosis is rare |
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sulfonamide-induced kernicterus in neonates
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sulfonamides dispalce bilirubin from albumin --> biliruhttp://www.flashcardexchange.com/mycards/add/1254997bin X BBB --> brain lesions
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sulfonamide crystalluria
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-rare with modern sulfa drugs
-hematuria is common early sign |
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useful controllable side effects of sulfonamides (3)
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1. hypoglycemia led to creation of sulfonylurea anti-diabetic drugs
2. systemic acidosis + alkaline urine led to creation of carbonic anhydrase inhibitors 3. sulfaguanine caused goiters in rats which led to creation of propylthiouracil (PTU), an antithyroid drug |
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sulfonamide resistance MOA
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overproduction of PABA which outcompetes sulfonamide antibiotics and still makes enough DHFA to survive
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what 2 drugs can you NOT give together to treat UTI
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methenamine + sulfonamide
-methenamine broken down into formaldehyde (the active drug) that treats UTI in acidic medium -when given together, methenamine and sulfonamide inactivate each other and form an inactive compound that precipitates |