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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
List the second generation cephalosporins.
Ceaclor Cefoxitin Cefuroxime
26
List the third generation cephalosporins.
Ceftriaxone Cefotaxime Cefpodoxime Ceftazidime
27
List the four generation cephalosporins.
Cefepime
28
List the five generation cephalosporins.
Ceftaroline
29
List the 4 carbapenems.
Imipenem Meropenem Ertapenem Doripenem
30
Imipenem (a carbapenem) must always be coadministered with this medication - why?
Cilastatin, an inhibitor of renal dehydropeptidase I - this decreases inactivation of the drug in renal tubules; meropenem is stable to dehydropeptidase
31
Antimicrobial AE - seizures?
Carbapenems (meropenem has a decreased risk)
32
MOA - aztreonam (a monobactam)?
Prevents peptidoglycan cross-linking by BINDING TO PENICILLIN-BINDING PROTEIN 3
33
Who is the ideal patient to be treated with aztreonam? Explain.
Patients with renal insufficiency who cannot tolerate aminoglycosides and patients who are allergic to penicillin (no cross-reactivity)
34
Which two antimicrobials are synergistic?
Aminoglycosides and beta-lactams (especially aztreonam)
35
Which two antimicrobials inhibit cell wall synthesis via a different mechanism than most in this category? What is their MOA?
Vancomycin and Bacitractin (glycopeptides) - inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursor
36
Explain the unique Cidal and Static MOA of Vancomycin.
Bactericidal against everything except C. difficile (Static)
37
Although it is well-tolerated in general, Vancomycin can have significant side effects - what are they and how might they be prevented?
Ototoxicity and Nephrotoxicity Thrombophlebitis Red man syndrome (diffuse flushing); preventable with anti-histamines and slow infusion rate
38
Mechanism of resistance to Vancomycin?
Bacterial amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac
39
What are the categories of anti-microbial protein synthesis inhibitors, and which part of the ribosome do they inhibit?
30S inhibitors: Aminoglycosides Tetracyclines 50S inhibitors: Chloramphenicol, Clindamycin Erythromycin (macrolides) Linezolid (variable) "Buy AT 30, CCEL (sell) at 50."
40
Which 30S inhibitor is static? Which is cidal?
AG - cidal | Tetracylines - static
41
List the 5 aminoglycosides.
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin "Mean (aminoglycoside) GNATS
42
Compare the details of the MOA of AG and tetracylines.
AG - cidal, irreversible inhibition of initiation complex formation TC - static, prevent attachment of aminoacyl-tRNA
43
Why are AG ineffective against anaerobes?
AG require oxygen for uptake
44
Mechanism of resistance of AG?
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenlyation
45
What are the major AE of aminoglycosides?
Nephrotoxicity/ototoxicity (especially with loop diuretics), neurmuscular blockade, teratogen
46
What is a particular indication of neomycin?
Bowel surgery
47
Mechanism of resistance - tetracylines?
Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
48
Contraindication of tetracyclines?
Milk, antacids, or iron-containing preparations - divalent cations inhibit the drugs' absorption in the gut
49
Which generation of cephalosporins can cross the BBB?
3rd generation
50
Which tetracycline should be used in patients with renal failure and why?
Doxycycline - fecally eliminated
51
MOA - chloramphenicol?
Blocks peptidyltranferase
52
Unique AE - chloramphenicol?
Dose DEPENDENT anemia, dose INDEPENDENT aplastic anemia
53
Mechanism of resistance to chloramphenicol?
Inactivation of the drug via a plasmid-encoded acetyltransferase
54
Which anti-microbial has limited use due to toxicity, but is still often used in developing countries due to its low cost?
Chloramphenicol
55
MOA - clindamycin? Which other class has a similar MOA?
Inhibits peptide transfer (translocation); macrolides
56
List the 3 macrolides. What is their MOA?
Azithromycin Clarithromycin Erythromycin Inhibits translocation (binds to the 23S rRNA of the 50S subunit)
57
Mechanism of resistance - macrolides
Methylation of 23S rRNA-binding site prevents binding of the dru
58
List the serious AE of macrolides.
GI motility issues, arrhythmia, acute cholestatic hepatitis, teratogen CYP450 inhibitor
59
Prophylaxis of gonococcal conjunctivitis in newborns?
Erythromycin ointment on the eyes
60
MOA - linezolid?
Prevents FORMATION of the initiation complex by binding 50S
61
Mechanism of resistance - linezolid?
Point mutation of rRNA
62
Specific indication of Fidaxomicin?
Repeat infections with C. difficile
63
MOA - Fidaxomicin?
Inhibits sigma subunit of RNA polymerase -> protein synthesis impairment and cell death
64
List the sulfonamides. What is their MOA?
Sulfamethoxazole (SMX) Sulfisoxazole Sulfadiazine MOA - inhibits dihydropteroate synthase (inhibits folic acid synthesis)
65
Mechanism of resistance to sulfonamides?
Altered enzyme, decreased uptake, increased PABA synthesis
66
Specific indication - dapsone?
Leprosy (both types) | P. jirovecii prophylaxis
67
MOA - trimethoprim?
Inhibits bacterial DHFR (inhibits folic acid synthesis)
68
Specific indications - TMP-SMX?
UTIs, Shigella, Salmonella, P. jirovecii, pneumonia
69
Prophylactic uses of TMP-SMX?
Pneumonia, toxoplasmosis, recurrent UTIs
70
List the fluoroquinolones.
Ciprofloxacin Levofloxacin (Etc - all end in oxacin)
71
MOA - fluoroquinolones
Inhibition of prokaryotic DNA gyrase (topoisomerase II) and topoisomerase IV)
72
Mechanism of resistance against FQs?
Mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
73
Prophylaxis for exposure to meningococcal infection?
Fluoroquinolones
74
MOA - daptomycin
Creates transmembrane channels in GP cocci, disrupting the cell membrane
75
MOA - metronidazole
Forms toxic free radical metabolites in the bacterial cell that damage DNA
76
MOA - rifampin/rifabutin
Inhibits mRNA synthesis via inhibition of the DNA-dependent RNA polymerase
77
AE - orange body fluids?
Rifampin
78
Why is rifabutin favored over rifampin in patients with HIV infection?
Less CYP450 stimulation
79
What are the prophylactic uses of rifampin?
Meningococcal; contacts of children with H. influenzae type B
80
MOA - isoniazid? What is required to convert isoniazid to an active metabolite?
Inhibit mycolic acid synthesis; bacterial catalase-peroxidase (encoded by KatG)
81
What vitamin must be given with Isoniazid? Why?
B6 - it can cause deficiency, leading to peripheral neuropathy, sideroblastic anemia, and pellagra
82
MOA - pyrazinamide?
Unknown; prodrug converted to active compound, works best at acidic pH
83
MOA - ethambutol?
Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
84
Unique AE - ethambutol?
Optic neuropathy (red-green color blindness)
85
What two anti-fungal medications target cell membrane integrity? What is the specific MOA?
Amphotericin B and Nystatin; bind ergosterol (unique to fungi), form pores that allow electrolyte leakage
86
Why must potassium and magnesium be supplemented with amphotericin B treatment?
Altered renal tubule permeability
87
MOA - flucytosine?
Inhibits DNA and RNA biosyntheis by conversion to 5-FU by cytosine deaminase
88
MOA - "azoles"?
Inhibit ergosterol (funal sterol) synthesis by inhibiting the CYP450 enzyme that converts lanosterol to ergosterol
89
MOA - terbinafine?
Inhibits lanosterol synthesis by inhibiting squalene epoxidase
90
List the echinocandins - what is their MOA?
Anidulafungin, Caspofungin, Micafungin ("fungin") - inhibit cell wall synthesis via inhibition of beta-glucan synthesis
91
MOA - griseofulvin?
Interferes with microtubule function, disrupts mitosis
92
Which anti-protozoan is used to treat toxoplasmosis?
Pyrimethamine
93
Which anti-protozoan is used to treat T. cruzi?
Nifurtimox
94
Which anti-protozoan is used to treat leishmaniasis?
Sodium stibogluconate
95
List the 3 drugs used to treat mites and lice. What are their MOAs?
1. Permethrin - neuronal membrane depolarization via sodium channels 2. Malathion - acetylcholinesterase inhibitor 3. Lindane - blocks GABA channels
96
MOA - chloroquine?
Blocks detoxification of heme into hemozoin; this causes accumulation of heme, which is toxic to plasmodia
97
Common AE of chloroquine?
Pruritis (also retinopathy)
98
MOA - mebendazole?
Microtubule inhibitor
99
List the drugs used to treat helminths.
``` Mebendazole Pyrantel pamoate Ivermectin Diethylcarbamazine Praziquantel ```
100
MOA and indication of Oseltamivir/Zanamivir
Influenza A and B | Inhibits NA, which decreases progeny release
101
Compare the MOA of acyclovir/famciclovir with ganciclovir. Which is more toxic?
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
MOA - foscarnet?
Inhibits viral DNA/RNA polymerase, HIV reverse transcriptase by binding to the pyrophosphate-binding site of the polymerase
103
Which anti-virals do not require any kinase activation?
Foscarnet, Cidofovir
104
MOA - cidofovir?
Inhibits viral DNA polymerase (preferential)
105
List the methods used to disinfect and sterilize.
1. Autoclave 2. Alcohols 3. Chlorhexidine 4. Hydrogen peroxide 5. Iodine and iodophors
106
Which disinfecting/sterilizing methods are sporicidal?
Hydrogen peroxide (maybe autoclave and iodine/idophors)
107
What is autoclave?
Pressured steam at >120 C
108
Which disinfecting/sterilizing methods denature proteins and disrupt cell membranes?
Alcohols and Chlorhexidine
109
Which disinfecting/sterilizing methods utilize free radical oxidation?
Hydrogen peroxide
110
What is the MOA of iodine and iodophors?
Halogenation of DNA, RNA, proteins
111
List the 7 NRTIs.
``` Abacavir (AbC) Didanosine (ddl) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir (TDF) Zidovudine (ZDV) ```
112
NRTIs - MOA?
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lacks a 3' OH)
113
Which NRTI inhibits nucleoTide binding?
Tenofovir (all others - nucleosides)
114
Of the NRTIs and NNRTIs, which need to be phosphorylated to be active?
NRTIs
115
Lis the 3 NNRTIs.
Delavirdine Efavirenz Nevirapine
116
NNRTIs - MOA?
Bind to reverse transcriptase; site is different from NRTIs
117
Major contraindication to Abacavir use?
Patients with HLA-B*5701 (increased risk of hyeprsensitivity)
118
Which NRTI can be used for general prophylaxis and during pregnancy to decrease risk of transmission?
Zidovudine
119
List the 7 protease inhibitors.
``` Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Ritonavir Saquinavir ``` All have "NAVIR"
120
MOA - protease inhibitors
Inhibits HIV-1 protease, which normally cleaves the polypeptide products into their functional parts; prevents maturation
121
Which protease inhibitor is used to boost other drug concentrations by inhibiting CYP450?
Ritonavir
122
List the 3 integrase inhibitors.
Raltegravir Elvitegravir Dolutegravir
123
List the 2 fusion inhibitors; compare their MOA.
Enfuvirtide - binds gp41, inhibits viral entry Maraviroc - binds CCR5 on T cells/monocytes, inhibits interactions with gp120
124
What are the main AE of interferons?
Flu-like symptoms, depression, neutropenia, myopathy
125
MOA - ribavirin?
Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
126
MOA - sofosbuvir?
Inhibits HCV RNA-dependent RNA polymerase (acts as a chain termpinator)
127
MOA - simeprevir?
HCV protease inhibitor; prevents viral replication

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