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Flashcards in Pharm antimicrobials 1 Deck (78):
1

gram negative organisms vs gram positive

gram negative:
-outer membrane (LPS endotoxin, outer membrane proteins for attachement and virulence, and porins)
-thin cell wall
-periplasmic space
gram positive:
-thick cell wall cross-linked by transpeptidase

2

what is the location of beta lactamase for gram negative? gram positive?

gram - : periplasmic space
gram + : secreted outside of cell

3

which gram - organisms are not covered by your typical drug regimen?

pseudomonas
(bacilli -> aerobic -> nonfermenters -> oxidase positive)

4

what drugs target the peptidoglycan cross-linking of the cell wall?

Beta-lactams (penicillin, penicillinase-sensitive penicillins, penicillinase-resistant penicillins, antipseudomonals, cephalosporins, carbapenems) and monobactams

5

what is the mechanism of action for beta lactams?

bind to penicillin-binding proteins (PBPs) which catalyze polymerization of the glycan strand

6

what are mechanisms of resistance to beta lactams?

enzymatic destruction (gram -'s - beta lactamase), reduced permeability (porin channel change), target site alteration (PBP change - gram +s)

7

what do beta lactams have a lack of activity against?

atypical organisms (mycoplasma pneumoniae and chlymydophilia pneumoniae (no cell wall))
MRSA

8

pharmacokinetics of beta lactams

short half lives, polar (go where water is), metabolized in liver, excretion by mostly renal system

9

side effects of beta lactams

1. hypersensitivity reactions (anaphylaxis, delayed hypersensitivity - rash, drug fever, acute interstitial nephritis, cross-reactivity)
2. seizures (high doeses in patients with renal dysfunction
3. GI effects (nausea, vomiting, diarrhea)

10

what are the natural penicillins?

penicillin G (IV and IM) and penicillin V (oral)

11

what spectrum do the natural penicillins cover?

mostly gram-positive aerobic organisms (streptococci, enterococcus, oral anaerobes, clostridium)
also n. meningitidis and t. pallidum (DOC for syphilis)

12

what are the anti-staphylococcal penicillins (penicillinase-resistant penicillins)

nafcillin, oxacillin, dicloxacillin (DON the STAPH!)
(i met a nasty ox with a beta lactam ring around its neck)

13

what does the penicillinase-resistant penicillins (anti-staphylococcal penicillins) have that make them penicillinase resistant?

bulky side chain sterically shielding the beta lactam ring (preventing degradation from penicillinase and prevents entry into the gram negative cell)

14

what is the spectrum of anti-staphylococcal penicillins (penicillinase-resistant penicillins)

MSSA (methicillin susceptible staph aureus)
streptococci

15

what is the oral anti-staphylococcal penicillin (penicillinase-resistant penicillin)

dicloxacillin

16

side effects of oxacillin

hepatotoxicity and neutropenia

17

side effects of nefcillin

similar to oxacillin (hepatotoxicity and neutropenia) + thrombophlebitis

18

aminopenicillins chemistry

amino group increases hydrophilicity causing improved penetration into gram-negative cell membrane

19

aminopenicillin spectrum

-gram positives: similar to penicillin with ampicillin as drug of choice for enterococci, listeria
-poor activity for gram - (still inhibited by penicillinase) covers e coli (some), proteus, salmonella, shigella, som eh influenza

20

what is the drug of choice for gram-positive enterococcus

ampicillin

21

what are the aminopenicillins?

amoxicillin and ampicillin

22

which aminopenicillin is best given orally?

amOxicillin

23

what are the clinical uses for amoxicillin?

otitis media, upper and lower respiratory tract infections in children, lyme

24

what are the clinical uses for ampicillin

listeria and enterococcal

25

adverse effects of aminopenicillins

GI, hypersensitivity (delayed)

26

what are the antipseudomonal penicillins?

piperacillin, ticarcillin

27

what are antipseudomonal penicillins used in combination with?

beta-lactamase inhibitor to expand spectrum to include beta-lactamase-producing organisms

28

what are the beta-lactamase inhibitors + anti-pseudomonal penicillins effective against?

broad coverage against the beta-lactamase producing gram-positivies (staph aureus), gram-negatives (h influenza) and anaerobes (bacteroides fragilis)

29

what are the beta-lactamase inhibitors?

clavulanic acid, sulbactam, tazobactam

30

what are the penicillins/beta-lactamase resistant combinations?

-amoxicillin and clavulanic acid
-ticarcillin and clavulanic acid
-ampicillin and sulbactam
-piperacillin and tazobactam

31

what are the drug combinations active against pseudomonas aeruginosa?

piperacillin and tazobactam
ticarcillin and clavulanic acid

32

what are the extended-spectrum penicillin/beta-lactamase inhibitor combinations used for clinically?

mixed infections
-intra-abdominal infections
-diabetic foot
-odontogenic infections
-animal and human bites
-aspiration pneumonia
-nosocomial pneumonia

33

which are the only cephalosporins that have activity against pseudomonas aeruginosa?

ceftazidime and cefeprime (cephalosporins)

34

what do cephalosporins lack activity against?

MRSA, enterococcus (except ceftaroline 5th gen) and b. fragilis

35

side effects of cephalosporing

hypersensitivity reactions (less common than penicillins), GI, coagulopathy (cefamandole, cefotetan, cefoperazone), disulfiram-like reaction with ethanole), CNS

36

what advantages do cephalosporins have over penicillins?

1. addition of a new basement makes the beta-lactam ring much more resistant to beta-lactamases
2. new R-group side chain allows for double the manipulations in the lab (more spectrum of activity)

37

spectrum of cephalosporins by generation

1. gram-positives
2. even across
3. gram-negative
4. good against gram-negative like 3rd but also good gram +
5. MRSA!!!

38

what are the first-generation cephalosporins

PH!!!!
-cephadroxil, cephalexin, CEFAZOLIN

39

mechanism to generations 1,2,3,4 cephalosporins

form a complex with a PBP, prevent extracellular transpeptidase activity; broader spectrum than penicillins

40

spectrum for first-generation cephalosporins

MSSA, streptococci, UTI bugs (e coli, proteus, klebsiella), mouth anaerobes (although activity against enterobacteriaceae shouldn't be assumed)

41

which first generation cephalosporin can be given IV?

cefazolin (used with surgical prophylaxis and serious MSSA infections)

42

when is cephalexin used?

UTI, SSTI

43

pharmacokinetics of first-generation cephalosporins

do not cross BBB

44

what are the second-generation cephalosporins?

fam, fur, fox, tea
cefamandole, cefuroxime, cefoxitin, cefotetan

45

what is the spectrum for second-generation cephalosporins?

gram-positive organisms (staph, strep)
gram negative (h flu, m catarrhalis, gonorrheae)
anaerobes
-used above and below diaphragm anaerobes

46

what are the third generation cephalosporins?

ceftazadime, ceftriazone, cefpodoxime

47

clinical uses ceftriaxone

-community acquired pneumonia with azithromycin
-meningitis
-uncomplicated UTI
-intra-abdominal infection with metronidazole
-CSF lyme
-strp endocarditis
-gonococcal infection and PID

48

ceftazidime clinical uses

definitive treatment of pseudomonas
-empiric treatment of post-neurosurgical miningitis

49

side effects of third generation cephalosporins

greatest correlation with c. difficile infection than other drugs

50

which third generation cephalosporin should not be used in neonates? why?

ceftriaxone (X FOR BABIES!)
biliary sludging, kernicterus, interaction with calcium-containing solutions causing precipitation

51

third-generation cephalosporins pharmacokinetics

widely distributed (polar) - effective penetration across BBB

52

what is the fourth generation cephalosporin?

cefepime

53

clinical uses of cefepime

nosocomial infections, neutropenic fever, meningitis (CNS*), UTI
3rd generation + staph coverage

54

cefepime side effects

akinetic seizures

55

5th generation cephalosporin

ceftaroline

56

what does ceftaroline cover?

gram + , gram - , MRSA!!!!
lacks activity against pseudomonas

57

cephalosporins/beta-lactamase inhibitor combinations

ceftolozane/tazobactam
ceftazidime/avibactam (more against enterobactericeae!!)
-increased activity against pseudomonas

58

which cephalosporins have excellent CSF penetration and can cover meningitis causing bacteria?

ceftriaxone (adults) and cefotaxime (children)

59

what are the carbapenems?

imipenem, meropenem, ertapenem, dorpenem

60

what is the class of carbapenems? mechanism?

cell wall syntehsis inhibitor
-similar mechanism to penicillins (attacks PBP)

61

ceftaroline mechanism

possesses a side chain that acts a "trojan horse" allowing access to PBP2a

62

carbapenams spectrum

broad spectrum excluding MRSA - resistant to beta-lactamases

63

what drug must be given with imipenem? why?

cilastatin - normal kidney has a dihydropeptidase that breaks imipenem down - cilastatin is a selective enzyme inhibitor of this dihydropeptidase is given

64

side effect imipenem

higher risk of seizures than other beta-lactams

65

side effects of carbapenams

renal failure if not dose adjusted

66

which carbapenam can be given outpatient due to its long half life?

ertapenem

67

what is the of choice for diabetic foot infections?

ertapenem (not effective against pseudomonas)

68

clinical uses carbapenems

complicated UTI, complicated intraabdominal infection, healthcare-acquired pneumonia, bone and SSTI, bacterial meningitis

69

what do carbapenems have significant interaction with?

valproic acid (VPA) - used to treat seizures

70

what class is aztreonam?

monobactam (cell wall synthesis inhibitor) with similar mechanism to penicillin

71

what is the spectrum of aztreonam?

gram - aerobic bacilli (if a tree falls on your house, you will feel negative)
NO GRAM + or ANAEROBES!!!

72

how is aztreonam used clinically?

definitive gram - therapy - not usually used as monotherapy (used with another drug that can cover gram +)

73

which beta-lactam drug can be used in patients with penicillin allergies?

aztreonam!! (the monobactam)

74

what are all the penicillin like drugs that are effective against pseudomonas?

pipercillin/tax, ticarcillin/clav, ceftazidine, cefepime, imipenem, aztretam

75

fourth generation cephalosporin spectrum

excellent activity against enterobacteriaceae (anaerobes) and pseudomonas

76

fourth generation cephalosporin (cefepime) chemistry and why is it beneficial?

zwitterion: neutral molecule with positive and negative charge that permits rapid entry into outer membrane of gram-negative bacteria

77

what are the organisms NOT covered by the 1st-4th generation cephalosporins?

LAME
listeria
atypicals
MRSA (ceftaroline covers)
enterococci

78

what must imipenem be administered with? why?

cilastatin - inhibitor of renal dehydropeptidase I (with imipenem "the kill is lastin' with cilastatin")
-imipenem is inactivated by dehydropeptidase I otherwise