Antibiotics-1

Front 1

where does stage 1 occur

Back 1

cytoplasm

Front 2

what drugs work at stage 1 of bacterial cell wall synthesis

Back 2

"F DC"
fosfamycin
D-cycloserine

Front 3

where does stage 2 occur

Back 3

cytoplasm --> outer leaf of cell membrane

Front 4

what drugs work at stage 2 of bacterial cell wall synthesis

Back 4

"VBT"
vancomycin, bacitracin, teichoplanin (same as vanco)

Front 5

where does stage 3 of bacterial cell wall synthesis occur

Back 5

cell wall

Front 6

what drugs work at stage 3 of bacterial cell wall synthesis

Back 6

beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactam)

Front 7

what bacteria are resistant to the antibiotics that inhibit cell wall synthesis? what are these antibiotics?

Back 7

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)

Front 8

sequence of stage 1 of bacterial cell wall synthesis

Back 8

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

Front 9

fosfomycin

Back 9

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

Front 10

D-cycloserine

-MOA
-reversibly inhibits___
-irreversibly inhibits___

Back 10

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!

Front 11

sequence of stage 2 of bacterial cell wall synthesis

Back 11

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

Front 12

bacitracin MOA (and stage)

Back 12

-works in stage 2 of bacterial cell wall synthesis
-inhibits recycling of transporter by preventing cleavage of one of the Pi's

Front 13

vancomycin MOA

Back 13

recognizes and sits on D-Ala-D-Ala so that the "brick" can't fit into cell wall acceptor molecule

Front 14

what must be present for vancomycin to work

Back 14

D-Ala-D-Ala terminal group

Front 15

how is vancomycin resistance developed

Back 15

bacteria replace D-Ala-D-Ala with D-Ala-D-lactate, so vancomycin doesn't recognize mutation

VRE (vancomycin-resistant enterococci) use this mechanism

Front 16

vancomycin administration

-IV for ___
-PO for ___ (try ____ first to prevent vanco resistance)
-for ____ infections try ____ first

Back 16

-IV for everything

-PO for pseudomembranous colitis (C.difficile), but use metronidazole first to prevent vancomycin resistance

for enterococcal infections, try ampicillin first

Front 17

vancomycin coverage & DOC

Back 17

serious G+ only!!!
no G- coverage
*DOC for MRSA/MRSE (with rifampin and/or gentamicin)
*DOC for ampicillin-resistant enterococcus (with gentamicin)

Front 18

vancomycin side effects/toxicities

Back 18

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

Front 19

teichoplanin

Back 19

same MOA & spectrum as vancomycin

Front 20

bacitracin MOA

Back 20

G+ ONLY
inhibits cell wall formation by preventing recycling of phospholipid carrier --> inhibition of Pi cleavage

Front 21

bacitracin administration

Back 21

topical only due to nephrotoxicity

Front 22

polymyxin MOA

Back 22

G- ONLY
cationic detergent that disrupts bacterial cell membrane --> no effect on cell wall synthesis

Front 23

polymyxin usually administered ____

-used ___ for ___, ___ and ___

Back 23

topically - nephro/ neurotoxicity when used IV

Polymyxin E and Polymyxin B used IV for:
-MDR pseudomonas aeruginosa
-ancinetobacter
-MDR ESBL-producing klebsiella

Front 24

sequence of stage 3 of bacterial cell wall synthesis

Back 24

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

Front 25

natural penicillins (2)

Back 25

penicillin G
penicillin V

Front 26

penG DOC for... (7)

hint: "PeniCilliNSS"

Back 26

-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)

Front 27

penG not used for...

Back 27

-UTI - no G- bacilli coverage (B.frag)
-C.diff - become quickly resistant
-Staph - most species produce penicillinases (cleave penG/penV)
-Gonococci - become quickly resistant

Front 28

PO choice penicillin

Back 28

penV

Front 29

IV/IM choice penicillin

Back 29

penG

Front 30

penG:
-1 of the worst for causing ___
-t1/2

Back 30

SEIZURES (imipenem is even worse)
short t1/2 (30 min) --> probenecid competes with renal secretor & prolongs penG's action

Front 31

penG depot formulations

Back 31

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

Front 32

penV

Back 32

-added methoxy group to benzene ring of penG
-PO only
-potassium salt (penVK)

**dose adjustment in renal failure

Front 33

penG aka

Back 33

benzyl penicillin

Front 34

penV aka

Back 34

phenoxymethyl penicillin

Front 35

penicillinase-resistant penicillins aka "anti-staph" or "B-lactamase resistant" penicillins

-treat ___ and ____ only
-MOA

Back 35

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

Front 36

methicill-IN

Back 36

-prototype drug: 1st penicillinase-resistant penicillin
-DO NOT GIVE PO (INtravenous only)
-causes IN: Interstitial Nephritis

Front 37

nafcillin

-elimination
-administration
-side effects

Back 37

-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

Front 38

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?

Back 38

-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)

Front 39

aminopenicillins (2)

Back 39

AA
ampicillin
amoxicillin

Front 40

aminopenicillins DOC for

hint: LEP

Back 40

Listeria
Enterococcus
Proteus mirabilis

Front 41

aminopenicillin coverage

Back 41

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)

Front 42

ampicillin

-take on ___stomach
-major side effect
-oral bioavailablity
-most likely to cause ___

Back 42

-take on EMPTY stomach
-major diarrhea: incomplete/erratic intestinal absorption
-low PO F
-MOST LIKELY to cause pseudomembranous colitis/superinfection

Front 43

amoxicillin

-administration

Back 43

-more lipophilic = PO choice
-lower concentration in gut when used to treat intestinal infections --> for salmonella/shigella, use ampicillin

Front 44

anti-pseudomonal penicillins (5)

Back 44

PM CAT: piperacillin, mezlocillin, carbenicillin, azlocillin, ticarcillin

Front 45

anti-pseudomonal penicillins used for

Back 45

-mainly serious, nosocomial G- bacilli infections

Front 46

uredopenicillins

Back 46

MAP: mezlocillin, azlocillin, piperacillin
-contain urea group
-hydrophilic = more affinity for porins of G- outer envelopes

Front 47

ticarcillin/carbenicillin

-structure
-main side effects (2)

Back 47

-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)

Front 48

timentin

Back 48

ticarcillin + clauvalanic acid

Front 49

carbenicillin prodrug

Back 49

-carbenicillin indanyl sodium
-the only PO formulation amongst PM CAT penicillins

Front 50

piperacillin

-best of all penicillins against___ and ____

Back 50

pseudominas aeruginosa and B.frag

GREAT for ANAEROBE coverage

Front 51

zosyn

-covers ___
-DOC for ___

Back 51

-piperacillin+tazobactam (B-lactamase inhibitor)

-covers B.frag
-DOC for non-meningital pseudomonas aeruginosa when combined with aminoglycoside for 2x coverage

Front 52

specific mechanisms of penicillin resistance (2)

Back 52

1. failure to reach PBPs
2. porin-deficient mutation

Front 53

how does failure to reach PBP confer penicillin resistance

Back 53

-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-

Front 54

how does porin-deficient mutation confer penicillin resistance

Back 54

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

Front 55

single most important method of penicillin resistance

Back 55

PRODUCTION OF B-LACTAMASE

Front 56

what are B-lactamases

Back 56

group of related enzymes elaborated by bacterial cells that are capable of hydrolyzing the B-lactam ring which inactivates antibiotic

Front 57

how does acquisition of altered PBPs reduce affinity for B-lactam antibiotics

Back 57

-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

Front 58

DOC for MRSA/MRSE

Back 58

vancomycin
-doesn't require transpeptidase to be present & not dependent on PBPs
-now seeing VRSA/VRSE

Front 59

efflux mechanisms

Back 59

-often seen in pseudomonas
-increased expression of P-GP (p-glycoprotein) efflux pump

Front 60

treatment of low-resistance strep. pneumoniae

Back 60

normal penG dose

Front 61

treatment of medium-resistance step. pneumoniae

Back 61

higher dose penG

Front 62

treatment of high-resistance step. pneumoniae

Back 62

-vancomycin + ceftriaxone
-levofloxacin/moxifloxacin are alternatives

Front 63

adverse reactions of penicillins

Back 63

SNL BB SIN
Sensitivity reactions
Neutropenia
Leukopenia

Bone marrow suppression
Bleeding

Seizures
Interstitial nephritis
Na+ overload/hypokalemia

Front 64

penicillin-induced sensitivity reactions

Back 64

-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

Front 65

if allergic to 1 penicillin...

Back 65

...allergic to ALL penicillins

Front 66

penicillin-induced leukopenia

Back 66

decreased WBC; rarely seen with all penicillins

Front 67

penicillin-induced neutropenia most likely with ____

Back 67

nafcillin (N/N)

Front 68

penicillin-induced prolonged bleeding time most likely with ___ and ___

Back 68

ticarcillin and carbenicillin

Front 69

which antibiotics cause penicillin-induced Na+ overload/hypokalemia

hint: anti-pseudomonal penicillins (2)

Back 69

-ticarcillin and carbenicillin
-caution in CHF/renal failure

Front 70

penicillin-induced seizures

Back 70

most likely penG

Front 71

penicillin-induced interstitial nephritis

Back 71

most likely methicillin

Front 72

penicillin-induced BM suppression most likely caused by___

Back 72

IV nafcillin
reversible

Front 73

cephalosporins

-MOA
-NOT cleaved by ___
-CAN give to pts allergic to ____

Back 73

-same MOA as penicillins: inhibit transpeptidase from cross-linking cell wall
-NOT cleaved by penicillinases
-give to pts allergic to CONDoM drugs

Front 74

cephalosporinases

Back 74

-1st generation more likely to be cleaved
-drugs become more resistant to cephalosporinases with increasing generation (4>3>2>1)

Front 75

ESBL

-found on ___
-cleave ___ and ___ with ___ group
-carried by ___ and ___ organisms

Back 75

-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

Front 76

Amp-C B-lactamase action on cephalosporins

Back 76

-Amp-C are chromosomal cephalosporinase elaborated by G-

-3rd generation ineffective against Amp-C
-4th generation (cefepime) relatively stable to Amp-C

Front 77

CASE organisms + DOC for their treatment

Back 77

Citrobacter freundii: Amp-C
Acinetobacter: no Amp-C
Serratia marcesans: Amp-C
Enterobacter cloacae: AmpC

DOC: carbapenems

Front 78

which cephalosporin effective against enterococcus sp. (G+)

Back 78

NONE!!!

Front 79

which cephalosporin effective against MRSA/MRSE

Back 79

NONE!!!

Front 80

2nd generation cephamycins stable to ___ &___ but not___or____

Back 80

stable to mild cephalosporinases and ESBL, but not to Amp-C or metallo-B-lactamases

Front 81

oral 1st generation cephalosporins (3)

Back 81

"Rad Alex Rox PO"
-cephRADine
-cephALEXin"
-cefadROXil

Front 82

3rd gen ceph's with biliary excretion

Back 82

sounds like "pair of tricks"

-cefoperazone
-ceftriaxone

Front 83

1st gen ceph's that cross BBB = 1st line for meningitis

Back 83

TRI-TAX-EPI-RAZ

-cefTRIaxone
-cefTAXime
-cefEPIme
-ceftRAZidime

Front 84

DO NOT use this 1st gen ceph for meningitis

Back 84

cefuroxime

Front 85

ceph's with MTT (methylthiotetrazole) side chain

Back 85

"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

Front 86

1st gen ceph's adverse effects

Back 86

"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

Front 87

1st gen ceph's USes

Back 87

USSS - UTI, Skin, Soft tissue, Surgical prophylaxis

Front 88

cefazolin

-__gen ceph
-administration
-used againST ___ and ___
-enters ____

Back 88

-1st gen
-IV extensive use againST STaph auerus/epidermitis and STrep pyogenes
-used during orthopedic surgery because ENTERS BONE

Front 89

2nd gen ceph's
-uses
-coverage

Back 89

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

Front 90

cefaclor frequent side effect

hint: side effects make you "sick"

Back 90

serum sickness

Front 91

cefuroxime axetil

Back 91

-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"

Front 92

cefPOdoxime

Back 92

-3rd gen ceph
-PO
-tx gonorrhea

Front 93

cefPrOzil

Back 93

-PO
-tx CART (community-acquired respiratory tract) infections

Front 94

loracarbef

Back 94

"carbacephem"
not used very often

Front 95

cephamycins

Back 95

-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

Front 96

cefmetazole

Back 96

seldom used bc of MTT side chain --> bleeding & disulfuram-like rxn with EtOH

Front 97

cefotetan

hint: has 2 t's...

Back 97

2nd longest t1/2 of all ceph's (ceftriaxone is #1) --> BID dosing

Front 98

cefoxitin

Back 98

-no longer considered reliable against B.frag; still used but for prophylaxis of abdominal surgery

Front 99

new DOC for severe peritonitis (appendicitis/diverticulitis) (6)

Back 99

-carbapenems
-piperacillin + tazobactam
-tigecycline
-metronidazole + ceftriaxone (3rd gen)
-metronidazole + quinolone
-ampicillin + sulbactam

Front 100

3rd gen ceph's uses

Back 100

-DOC for serious nosocomial G- especially with enterobacteriaceae
-Neisseria meningitidis
-respiratory infections & sepsis (lung origin)
-penetrate better into eye & CNS

Front 101

3rd gen ceph's

-excellent coverage of ____ and ____
-empirical treatment of ____ and ____
-less effective than 1st/2nd gen for ____

Back 101

-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

Front 102

ceph's that tx meningitis (cross BBB)

Back 102

"FURious OX and TAZ TRIed EPI in a TAXI"

-ceFUROXime
-cefTAZidime
-cefTRIaxone
-cefEPIme
-cefoTAXIme

Front 103

what 3rd gen ceph's are active against weaker anaerobes (2)

Back 103

"my country TIZ of me, that's why it TAXes me"
-Cefotaxime
-Ceftizoxime

*not clinically significant --> not 1st/2nd line tx for any anaerobe

Front 104

3rd gen ceph that covers B.frag

hint: "tiz fragile"

Back 104

ceftizoxime

Front 105

ceftriaxone

-dosing
-price
-t1/2
-coverage

Back 105

-superstar!!!
-generic and QD dosing
-longest t1/2 of all ceph's
-covers wimpy G+ anaerobes but not DOC

Front 106

ceftriaxone is DOC for ____ & _____

Back 106

Neisseria gonorrhea & penicillin-resistant strep pneumoniae (+ vanco for G+)

Front 107

ceftriaxone excretion

Back 107

60% biliary, 40% urinary
in renal/liver failure, elimination will switch over to healthy organ

Front 108

ceftriaxone common side effect

Back 108

biliary sludging

Front 109

cefotaxime is alternative to ____ for ______

-covers ___
-lacks ___

Back 109

-alternative to ceftriaxone for penicillin-resistant strep pneumoniae
-covers wimpy G+ anaerobes but not DOC
-no biliary sludging (unlike ceftriaxone)

Front 110

cefoperaZONE

-treats____ but NOT____ (caused by same bug)...BBB
-excretion
-structure

Back 110

-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)

Front 111

ceftazidime

-effective against___
-DOC for___
-susceptible to ___

Back 111

-pseudomonas aeruginosa
-X BBB --> DOC for pseudomonal meningitis
-easiest ceph to be cleaved by ESBL

Front 112

peripheral pseudomonas aeruginosa tx (non-meningital)

Back 112

always 2x coverage!!!
-piperacillin/tazobactam (zosyn) + aminoglycoside

Front 113

ESBL-producing pseudomonas aeruginosa tx

Back 113

-cefepime (4th gen) X BBB & resistant to ESBL

Front 114

the 3 MOST IMPORTANT 3rd gen parenteral ceph's

Back 114

"T's"
-cefTriaxone
-cefoTaxime
-cefTaxidime

Front 115

4th gen ceph coverage

Back 115

-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)

Front 116

cefepime is MORE stable against B-lactamases of ___ organisms (____and ____)

Back 116

G-
Amp-C (CS+E of CASE organisms) and ESBL

Front 117

cefepime gets thru ____ because its a _____

Back 117

porins of G- envelopes
zwitterion

Front 118

cefepime is DOC for ____ because it crosses ____ and is resistant to ___

Back 118

pseudomonal meningitis
BBB
ESBL

Front 119

cefepime administration

Back 119

BID, parenteral only

Front 120

carbapenems (3) & their coverage

Back 120

"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

Front 121

imipenem coverage

Back 121

"gorilla-cillin"
-G+, G-, anaerobes, B.frag, pseudomonas aeruginosa (but NOT pseudomonal sp), enterococcus faecalis (but NOT enterococcus faecium)

Front 122

imipenem DOC for...

hint: IMIP = IMakeIncrediblePastries

Back 122

"CAKES" = CASE organisms + klebsiella
-Citrobacter (Amp-C)
-Acinetobacter
-Klebsiella (ESBL producing)
-Enterobacter (Amp-C)
-Serratia (Amp-C)

Front 123

imipenem is cleaved by____

Back 123

metallo-B-lactamases

bright side: very rare :o)

Front 124

imipenem administration

Back 124

IV only + expensive - save for MDR infections, CASE organisms, & empirical therapy for serious infections

Front 125

imipenem metabolism

Back 125

-metabolized to nephrotoxic substance by renal dehydropeptidases
-give equal amounts of CILASTATIN (inhibitor of brush border dehydropeptidases)
-imipenem+cilastatin= Primaxin

Front 126

imipenem uses

Back 126

"LUIG-E, MD. - POLYspecialist in BACK and BONE

-Lower resp.
-UTI
-Intra-abdominal
-Gynecological
-Endocarditis

-MDR organisms

-POLYmicrobial

-BACterial septicemia
-BONE, joint and skin

Front 127

imipenem adverse effect/cross sensitivity

Back 127

-SEIZURES (higher than with penG)
-more common in renal failure
-don't use in children (seizure risk)
-cross sensitivity with penicillin allergies

Front 128

meropenem

Back 128

-NO cilastatin needed
-NO seizures
-CAN use in children

Front 129

ertapenem

Back 129

"monkey-cillin"
-NO activity against "APE" --> Acinetobacter, Pseudomonas, Enterococcus sp
-NO cilastatin needed
-use for MDR E.coli, pyelonephritis

Front 130

monobactam

Back 130

aztreonam

Front 131

aztreonam MOA

Back 131

-irreversibly inhibits PBP-3 which forms septum during bacterial division

Front 132

aztreonam coverage

Back 132

- G- aerobes (pseudomonas aeruginosa)
-B-lactamases, Amp-C, metallo-B-lactamases

-NOT G+ anaerobes
-NOT ESBL (chemical structure has oxyimino moiety)

Front 133

aztREonam excretion

Back 133

-renal (majority)
-NO dose adjustment needed for renal failure :o)

Front 134

aztreonam cross-sensitivity

Back 134

-very rare!
-CAN use with penicillin allergies
-LEAST cross-sensitivity amongst all B-lactam antibiotics

Front 135

aztreonam use

Back 135

-reserve for serious G- infections
-lung, bone, UTI, blood

Front 136

B-lactamase inhibitors

Back 136

-minimal/NO antibacterial activity on their own
-always combined with B-lactam antibiotic

Front 137

-which B-lactamases are susceptible to B-lactamase inhibitors?

-which B-lactamases are NOT susceptible?

Back 137

-penicillinase, cephalosporinase, ESBL

-NOT for Amp-C (use imipenem/meropenem for CSE)
-NOT for metallo-B-lactamases

Front 138

amoxicillin + clavulanic acid

Back 138

augmentin
**the only PO product

Front 139

ticarcillin + clavulanic acid

not good for ___

Back 139

timentin

kelbsiella

Front 140

ampicillin + sUlbactam

Back 140

unasyn

Front 141

piperacillin + taZObactam
not good for ____

Back 141

zosyn
klebsiella

Front 142

penicillins DO NOT distribute well into...(5)

Back 142

-eye
-brain/CNS
-joint
-bone
-prostate

Front 143

which generation ceph's can penetrate CNS

Back 143

3rd and 4th gen CAN X BBB
1st and 2nd gen CAN'T X BBB

Front 144

what is the major pathway of elimination for most penicillins, cephalosporins, carbapenems and aztreonam

Back 144

RENAL

Front 145

what drug is co-administered that competes for serum protein binding sites and increase the amount of FREE antibiotic available to kill bacteria

Back 145

probenecid

Front 146

penicillins have ___ half-lives

Back 146

short
dose q3-4h

Front 147

which antibiotics do NOT require dose adjustment in renal failure (6)

hint: 4 B-lactamase resistant penicillins and 2 3rd gen ceph's

Back 147

-COND: cloxacillin, oxacillin, nafcillin, dicloxacillin
-ceftriaxone
-cefoperazone

Front 148

cephalosporins half-life

Back 148

-longer than penicillins
-ceftriaxone = LONGEST

**TRIAthalons are LONG

Front 149

penicillins and cephalosporins are secreted into ___ to some extent
-common side effect
-risk for ___
-caution in ___

Back 149

BILE
**diarrhea always present
**risk of superinfection
**caution in liver failure - drug accumulates and causes toxicity

Front 150

which antibiotics have biliary excretion component

hint: 3 classes of B-lactamase antibiotics

Back 150

-COND: cloxacillin, oxacillin, nafcillin, dicloxacillin
-PM CAT (anti-pseudomonal): piperacillin, mezlocillin, carbenicillin, azlocillin, ticarcillin
-cefoperazone
-ceftriaxone

Front 151

what are the chances of developing hypersensitivity reaction to a cephalosporin if you are NOT allergic to penicillin

Back 151

1-3%

Front 152

what are the chances of developing hypersensitivity to cephalosporin if you ARE allergic to penicillin

Back 152

7-8%

Front 153

what is the initial step in eliciting an immune response to an antibiotic

Back 153

formation of antigen

Front 154

sequence of events of eliciting an allergic response

Back 154

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

Front 155

aminopenicillins coverage

Back 155

SS HEMP +B

Salmonella
Shigella
H.flu
E.coli
MCAT
Proteus mirabilis
B.frag (G-bacilli: must combine with B-lactamase inhibitor)

Front 156

T/F: aminopenicillins are resistant against B-lactamase

Back 156

FALSE!

Front 157

aminopenicillins are effective against G- because they're ____ thus able to pass thru ____

Back 157

zwitterions
porins of G- envelopes

Front 158

which organisms are susceptible to antipseudomonal penicillins

hint: PIB

Back 158

-pseudomonas aeruginosa (with B-lactamase inhibitor + aminoglycoside)

-indole + proteus

-B.frag (with B-lactamase inhibitor)

Front 159

which organisms are NOT susceptible to antipseudomonal penicillins

hint: BLacK

Back 159

-B-lactamase

-Klebsiella

Front 160

oral penicillins

Back 160

-penV
-amoxicillin
-ampicillin
-dicloxacillin
-carbenicillin (indanyl sodium formulation only)

Front 161

G+ B-lactamase production

Back 161

-B-lactamases secreted outside the cell into surrounding media
-encoded by plasmids AND chromosomes

Front 162

G- B-lactamase production

Back 162

-B-lactamases concentrated in the periplasmic space between envelope and cytoplasmic membrane
-encoded by plasmids OR chromosomes

Front 163

"foxes get dirty"

Back 163

ceFOXitin is the DOC for "dirty surgery" - abdominal surgery where potential for mixed infections exists

Front 164

1st gen ceph coverage

Back 164

-G+
-some G- "PEcK"

Proteus mirabilis
E.coli
Klebsiella

Front 165

2nd gen ceph coverage

Back 165

-less G+
-more G- "HEN PEcK"

H.flu
Enterobacter
Neisseria
Proteus mirabilis
E.coli
Klebsiella

Front 166

3 most important things about METal TAN FOX

Back 166

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

Front 167

in what form is an acidic drug found in the body when its pH>pKa

Back 167

ionized

Front 168

in what form is an acidic drug found in the body when its pH<pKa

Back 168

unionized; this is what happened with the original parent sulfanilamide drug because of its low solubility/high pKa

Front 169

for every 1 pH unit decrease in the surrounding area of the drug, what happens to the absolute amount of unionized drug

Back 169

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

Front 170

toxic side effect of original sulfanilamide parent drug

Back 170

low pH of the urine and high pKa of the drug = [high] of unionized drug = precipitation = crystalluria

Front 171

2 ways to prevent crystalluria

Back 171

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

Front 172

sulfonamide MOA

Back 172

inhibition of dihydropteroate synthetase

para-aminophenyl-sulfonamide moiety resembles PABA --> bacteria can't make thymidylate (T) --> can't make dihydrofolic acid (DHFA) --> bacteriostatic

Front 173

dapsone

Back 173

sulfone antibiotic used to treat leporsy

Front 174

para-aminosalicylic acid (PAS)

Back 174

sulfonamide antibiotic used to treat TB; very similar structure to PABA --> same MOA as sulfonamides

Front 175

sulfonamide absorption

Back 175

from intestine

Front 176

sulfonamide distribution

Back 176

-pass into ALL body fluids/tissues
-X BBB

Front 177

sulfonamide metabolism

Back 177

-not extensively metabolized
-mainly by acetylation of primary amino group on aromatic ring

Front 178

sulfonamide elimination

Back 178

renally

Front 179

sulfonamide adverse effects

Back 179

CRYSTAL KERN likes wearing HYPERshort HEMlines

-crystalluria
-kernicterus (neonates)
-hypersensitivity reactions
-hematopoietic rxns

Front 180

sulfonamide hypersensitivity reactions

Back 180

-Steven-Johnson syndrome
-present on 9th day of tx; consequent exposure causes immediate rxn
-more common with long-acting sulfonamides

Front 181

if you're allergic to 1 sulfonamide...

Back 181

...you're allergic to ALL of them

Front 182

sulfonamide hematopoietic reactions

Back 182

-hemolytic anemia in glu-6-phosphate dehydrogenase deficiency (G6PDD)

-agranulocytosis is rare

Front 183

sulfonamide-induced kernicterus in neonates

Back 183

sulfonamides dispalce bilirubin from albumin --> biliruhttp://www.flashcardexchange.com/mycards/add/1254997bin X BBB --> brain lesions

Front 184

sulfonamide crystalluria

Back 184

-rare with modern sulfa drugs
-hematuria is common early sign

Front 185

useful controllable side effects of sulfonamides (3)

Back 185

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

Front 186

sulfonamide resistance MOA

Back 186

overproduction of PABA which outcompetes sulfonamide antibiotics and still makes enough DHFA to survive

Front 187

what 2 drugs can you NOT give together to treat UTI

Back 187

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