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Antimicrobials Flashcards

1
Q

Antimicrobial classes targeting peptidoglycan cross-linking (6)

A
  1. Pencillinase-sensitive penicillins
  2. Penicillanse-resistant penicillins
  3. Antipseudomonal
  4. Cephalosporins (I-V)
  5. Carbapenems
  6. Monobactams
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2
Q

MOA of penicillin G, V? Cidal or Static? What other drugs have the same MOA?

A

Bactericidal - D-Ala-D-Ala structural analog binds penicillin-binding proteins, blocking transpeptidase cross-linking of peptidoglycan in the cell wall (also activates autolytic enzymes)

Shared with:

  1. Ampicillin, amoxicillin, aminopenicillin
  2. Dicloxacillin, nafcillin, oxacillin
  3. Piperacillin, ticarcillin
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3
Q

Which penicillins are penicillinase sensitive? Resistant?

A

Sensitive - penicillin G, V, amipicillin/amoxicillin/aminopenicillin

Resistant - oxacillin/nafcillin/dicloxacillin, antipseudomonals (ticarcillin, piperacillin)

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4
Q

What structural feature confers penicillinase resistance?

A

Bulky R group blocking access of beta-lactamase to beta-lactam ring

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5
Q

Prophylactic treatment for pregnant women carrying GBS?

A

Intrapartum penicillin G or ampicillin

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6
Q

Prophylactic treatment for strep pharyngitis in a child with prior rheumatic fever?

A

Benzathine penicillin G or oral penicillin V

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7
Q

Prophylactic treatment for exposure to syphilis?

A

Benzathine penicillin G

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8
Q

Anti-microbial AE - direct Coombs positive hemolytic anemia?

A

Penicillin G, V

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9
Q

Mechanism of resistance - penicillin G, V? Others with this mechanism?

A

Bacterial penicillinase (type of beta-lactamase) cleaves the beta-lactam ring

+ ampicillin/amoxicillin/aminopenicillin, piperacillin/ticarcillin

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10
Q

Possible AE common to all penicillins?

A

Hypersensitivity reactions

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11
Q

Anti-microbial AE - pseudomembranous colitis?

A

Ampicillin/amoxicillin/aminopenicillin

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12
Q

Prophylactic treatment for patients at high risk for endocarditis and undergoing surgical or dental procedures?

A

Amoxicillin

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13
Q

Mechanism of resistance - dicloxacillin/nafcillin/oxacillin?

A

Altered penicillin-binding protein target site (MRSA)

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14
Q

Anti-microbial AE - interstitial nephritis?

A

Dicloxacillin/nafcillin/ oxacillin

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15
Q

List the 4 beta-lactamase inhibitors. What is their MOA/function?

A

Clavulanic acid
Avibactam
Sulfbactam
Tazobactam

Inhibit beta-lactamase (like penicillinase), given with penicillins to protect from destruction by beta-lactamase

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16
Q

MOA - cephalosporins?

A

Inhibit cell wall synthesis; less susceptible to penicillinases

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17
Q

Antimicrobial AE - vitamin K deficiency

A

Cephalosporins

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18
Q

This class of anti-microbials increases the nephrotoxicity of aminoglycosides

A

Cephalosporins

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19
Q

Mechanism of resistance - cephalosporins?

A

Structural change in penicillin-binding proteins via transpeptidases

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20
Q

True or false - cephalosporins can be given to penicillin-allergic patients.

A

True - they have a low rate of cross-reactivity

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21
Q

Prophylaxis given before surgery to prevent S. aureus wound infections?

A

Cefazolin (1st Gen)

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22
Q

Which generation of cephalosporins is used to treat serious gram negative infections resistant to other beta-lactams?

A

Third generation (ceftriaxone, cefotaxime, cefpodoxime, ceftazidime)

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23
Q

Prophylaxis for those exposed to gonorrhea and meningoccocal infection?

A

Ceftriaxone

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24
Q

List the first generation cephalosporins.

A

Cefazolin

Cephalexin

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25
Q

List the second generation cephalosporins.

A

Ceaclor
Cefoxitin
Cefuroxime

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26
Q

List the third generation cephalosporins.

A

Ceftriaxone
Cefotaxime
Cefpodoxime
Ceftazidime

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27
Q

List the four generation cephalosporins.

A

Cefepime

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28
Q

List the five generation cephalosporins.

A

Ceftaroline

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29
Q

List the 4 carbapenems.

A

Imipenem
Meropenem
Ertapenem
Doripenem

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30
Q

Imipenem (a carbapenem) must always be coadministered with this medication - why?

A

Cilastatin, an inhibitor of renal dehydropeptidase I - this decreases inactivation of the drug in renal tubules; meropenem is stable to dehydropeptidase

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31
Q

Antimicrobial AE - seizures?

A

Carbapenems (meropenem has a decreased risk)

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32
Q

MOA - aztreonam (a monobactam)?

A

Prevents peptidoglycan cross-linking by BINDING TO PENICILLIN-BINDING PROTEIN 3

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33
Q

Who is the ideal patient to be treated with aztreonam? Explain.

A

Patients with renal insufficiency who cannot tolerate aminoglycosides and patients who are allergic to penicillin (no cross-reactivity)

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34
Q

Which two antimicrobials are synergistic?

A

Aminoglycosides and beta-lactams (especially aztreonam)

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35
Q

Which two antimicrobials inhibit cell wall synthesis via a different mechanism than most in this category? What is their MOA?

A

Vancomycin and Bacitractin (glycopeptides) - inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursor

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36
Q

Explain the unique Cidal and Static MOA of Vancomycin.

A

Bactericidal against everything except C. difficile (Static)

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37
Q

Although it is well-tolerated in general, Vancomycin can have significant side effects - what are they and how might they be prevented?

A

Ototoxicity and Nephrotoxicity
Thrombophlebitis
Red man syndrome (diffuse flushing); preventable with anti-histamines and slow infusion rate

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38
Q

Mechanism of resistance to Vancomycin?

A

Bacterial amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac

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39
Q

What are the categories of anti-microbial protein synthesis inhibitors, and which part of the ribosome do they inhibit?

A

30S inhibitors:
Aminoglycosides
Tetracyclines

50S inhibitors:
Chloramphenicol, Clindamycin
Erythromycin (macrolides)
Linezolid (variable)

“Buy AT 30, CCEL (sell) at 50.”

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40
Q

Which 30S inhibitor is static? Which is cidal?

A

AG - cidal

Tetracylines - static

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41
Q

List the 5 aminoglycosides.

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

“Mean (aminoglycoside) GNATS

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42
Q

Compare the details of the MOA of AG and tetracylines.

A

AG - cidal, irreversible inhibition of initiation complex formation

TC - static, prevent attachment of aminoacyl-tRNA

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43
Q

Why are AG ineffective against anaerobes?

A

AG require oxygen for uptake

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44
Q

Mechanism of resistance of AG?

A

Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenlyation

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45
Q

What are the major AE of aminoglycosides?

A

Nephrotoxicity/ototoxicity (especially with loop diuretics), neurmuscular blockade, teratogen

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46
Q

What is a particular indication of neomycin?

A

Bowel surgery

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47
Q

Mechanism of resistance - tetracylines?

A

Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps

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48
Q

Contraindication of tetracyclines?

A

Milk, antacids, or iron-containing preparations - divalent cations inhibit the drugs’ absorption in the gut

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49
Q

Which generation of cephalosporins can cross the BBB?

A

3rd generation

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50
Q

Which tetracycline should be used in patients with renal failure and why?

A

Doxycycline - fecally eliminated

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51
Q

MOA - chloramphenicol?

A

Blocks peptidyltranferase

52
Q

Unique AE - chloramphenicol?

A

Dose DEPENDENT anemia, dose INDEPENDENT aplastic anemia

53
Q

Mechanism of resistance to chloramphenicol?

A

Inactivation of the drug via a plasmid-encoded acetyltransferase

54
Q

Which anti-microbial has limited use due to toxicity, but is still often used in developing countries due to its low cost?

A

Chloramphenicol

55
Q

MOA - clindamycin? Which other class has a similar MOA?

A

Inhibits peptide transfer (translocation); macrolides

56
Q

List the 3 macrolides. What is their MOA?

A

Azithromycin
Clarithromycin
Erythromycin

Inhibits translocation (binds to the 23S rRNA of the 50S subunit)

57
Q

Mechanism of resistance - macrolides

A

Methylation of 23S rRNA-binding site prevents binding of the dru

58
Q

List the serious AE of macrolides.

A

GI motility issues, arrhythmia, acute cholestatic hepatitis, teratogen

CYP450 inhibitor

59
Q

Prophylaxis of gonococcal conjunctivitis in newborns?

A

Erythromycin ointment on the eyes

60
Q

MOA - linezolid?

A

Prevents FORMATION of the initiation complex by binding 50S

61
Q

Mechanism of resistance - linezolid?

A

Point mutation of rRNA

62
Q

Specific indication of Fidaxomicin?

A

Repeat infections with C. difficile

63
Q

MOA - Fidaxomicin?

A

Inhibits sigma subunit of RNA polymerase -> protein synthesis impairment and cell death

64
Q

List the sulfonamides. What is their MOA?

A

Sulfamethoxazole (SMX)
Sulfisoxazole
Sulfadiazine

MOA - inhibits dihydropteroate synthase (inhibits folic acid synthesis)

65
Q

Mechanism of resistance to sulfonamides?

A

Altered enzyme, decreased uptake, increased PABA synthesis

66
Q

Specific indication - dapsone?

A

Leprosy (both types)

P. jirovecii prophylaxis

67
Q

MOA - trimethoprim?

A

Inhibits bacterial DHFR (inhibits folic acid synthesis)

68
Q

Specific indications - TMP-SMX?

A

UTIs, Shigella, Salmonella, P. jirovecii, pneumonia

69
Q

Prophylactic uses of TMP-SMX?

A

Pneumonia, toxoplasmosis, recurrent UTIs

70
Q

List the fluoroquinolones.

A

Ciprofloxacin
Levofloxacin
(Etc - all end in oxacin)

71
Q

MOA - fluoroquinolones

A

Inhibition of prokaryotic DNA gyrase (topoisomerase II) and topoisomerase IV)

72
Q

Mechanism of resistance against FQs?

A

Mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps

73
Q

Prophylaxis for exposure to meningococcal infection?

A

Fluoroquinolones

74
Q

MOA - daptomycin

A

Creates transmembrane channels in GP cocci, disrupting the cell membrane

75
Q

MOA - metronidazole

A

Forms toxic free radical metabolites in the bacterial cell that damage DNA

76
Q

MOA - rifampin/rifabutin

A

Inhibits mRNA synthesis via inhibition of the DNA-dependent RNA polymerase

77
Q

AE - orange body fluids?

A

Rifampin

78
Q

Why is rifabutin favored over rifampin in patients with HIV infection?

A

Less CYP450 stimulation

79
Q

What are the prophylactic uses of rifampin?

A

Meningococcal; contacts of children with H. influenzae type B

80
Q

MOA - isoniazid? What is required to convert isoniazid to an active metabolite?

A

Inhibit mycolic acid synthesis; bacterial catalase-peroxidase (encoded by KatG)

81
Q

What vitamin must be given with Isoniazid? Why?

A

B6 - it can cause deficiency, leading to peripheral neuropathy, sideroblastic anemia, and pellagra

82
Q

MOA - pyrazinamide?

A

Unknown; prodrug converted to active compound, works best at acidic pH

83
Q

MOA - ethambutol?

A

Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase

84
Q

Unique AE - ethambutol?

A

Optic neuropathy (red-green color blindness)

85
Q

What two anti-fungal medications target cell membrane integrity? What is the specific MOA?

A

Amphotericin B and Nystatin; bind ergosterol (unique to fungi), form pores that allow electrolyte leakage

86
Q

Why must potassium and magnesium be supplemented with amphotericin B treatment?

A

Altered renal tubule permeability

87
Q

MOA - flucytosine?

A

Inhibits DNA and RNA biosyntheis by conversion to 5-FU by cytosine deaminase

88
Q

MOA - “azoles”?

A

Inhibit ergosterol (funal sterol) synthesis by inhibiting the CYP450 enzyme that converts lanosterol to ergosterol

89
Q

MOA - terbinafine?

A

Inhibits lanosterol synthesis by inhibiting squalene epoxidase

90
Q

List the echinocandins - what is their MOA?

A

Anidulafungin, Caspofungin, Micafungin (“fungin”) - inhibit cell wall synthesis via inhibition of beta-glucan synthesis

91
Q

MOA - griseofulvin?

A

Interferes with microtubule function, disrupts mitosis

92
Q

Which anti-protozoan is used to treat toxoplasmosis?

A

Pyrimethamine

93
Q

Which anti-protozoan is used to treat T. cruzi?

A

Nifurtimox

94
Q

Which anti-protozoan is used to treat leishmaniasis?

A

Sodium stibogluconate

95
Q

List the 3 drugs used to treat mites and lice. What are their MOAs?

A
  1. Permethrin - neuronal membrane depolarization via sodium channels
  2. Malathion - acetylcholinesterase inhibitor
  3. Lindane - blocks GABA channels
96
Q

MOA - chloroquine?

A

Blocks detoxification of heme into hemozoin; this causes accumulation of heme, which is toxic to plasmodia

97
Q

Common AE of chloroquine?

A

Pruritis (also retinopathy)

98
Q

MOA - mebendazole?

A

Microtubule inhibitor

99
Q

List the drugs used to treat helminths.

A 
Mebendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazine
Praziquantel
100
Q

MOA and indication of Oseltamivir/Zanamivir

A

Influenza A and B

Inhibits NA, which decreases progeny release

101
Q

Compare the MOA of acyclovir/famciclovir with ganciclovir. Which is more toxic?

A

Both are anti-virals that inhibit nucleic acid synthesis as guanosine analogs. Both preferentially inhibit viral DNA polymerase.

A/F - monophosphorylated by thymidine kinase; triphosphate formed by cellular enzymes

G - monophosphorylated by viral kinase; triphosphate formed by cellular kinase

G is more toxic.

102
Q

MOA - foscarnet?

A

Inhibits viral DNA/RNA polymerase, HIV reverse transcriptase by binding to the pyrophosphate-binding site of the polymerase

103
Q

Which anti-virals do not require any kinase activation?

A

Foscarnet, Cidofovir

104
Q

MOA - cidofovir?

A

Inhibits viral DNA polymerase (preferential)

105
Q

List the methods used to disinfect and sterilize.

A
  1. Autoclave
  2. Alcohols
  3. Chlorhexidine
  4. Hydrogen peroxide
  5. Iodine and iodophors
106
Q

Which disinfecting/sterilizing methods are sporicidal?

A

Hydrogen peroxide (maybe autoclave and iodine/idophors)

107
Q

What is autoclave?

A

Pressured steam at >120 C

108
Q

Which disinfecting/sterilizing methods denature proteins and disrupt cell membranes?

A

Alcohols and Chlorhexidine

109
Q

Which disinfecting/sterilizing methods utilize free radical oxidation?

A

Hydrogen peroxide

110
Q

What is the MOA of iodine and iodophors?

A

Halogenation of DNA, RNA, proteins

111
Q

List the 7 NRTIs.

A 
Abacavir (AbC)
Didanosine (ddl)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (ZDV)
112
Q

NRTIs - MOA?

A

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lacks a 3’ OH)

113
Q

Which NRTI inhibits nucleoTide binding?

A

Tenofovir (all others - nucleosides)

114
Q

Of the NRTIs and NNRTIs, which need to be phosphorylated to be active?

A

NRTIs

115
Q

Lis the 3 NNRTIs.

A

Delavirdine
Efavirenz
Nevirapine

116
Q

NNRTIs - MOA?

A

Bind to reverse transcriptase; site is different from NRTIs

117
Q

Major contraindication to Abacavir use?

A

Patients with HLA-B*5701 (increased risk of hyeprsensitivity)

118
Q

Which NRTI can be used for general prophylaxis and during pregnancy to decrease risk of transmission?

A

Zidovudine

119
Q

List the 7 protease inhibitors.

A 
Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Ritonavir
Saquinavir

All have “NAVIR”

120
Q

MOA - protease inhibitors

A

Inhibits HIV-1 protease, which normally cleaves the polypeptide products into their functional parts; prevents maturation

121
Q

Which protease inhibitor is used to boost other drug concentrations by inhibiting CYP450?

A

Ritonavir

122
Q

List the 3 integrase inhibitors.

A

Raltegravir
Elvitegravir
Dolutegravir

123
Q

List the 2 fusion inhibitors; compare their MOA.

A

Enfuvirtide - binds gp41, inhibits viral entry

Maraviroc - binds CCR5 on T cells/monocytes, inhibits interactions with gp120

124
Q

What are the main AE of interferons?

A

Flu-like symptoms, depression, neutropenia, myopathy

125
Q

MOA - ribavirin?

A

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

126
Q

MOA - sofosbuvir?

A

Inhibits HCV RNA-dependent RNA polymerase (acts as a chain termpinator)

127
Q

MOA - simeprevir?

A

HCV protease inhibitor; prevents viral replication

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