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Chemotherapy > Mechanism of Resistance > Flashcards

Mechanism of Resistance Flashcards

1
Q

Penicillins

A

Beta-lactamases (Plasmid-mediated)
Decreased permeability of the drugs through variable outer membranes (chromosome mediated)
Mutant and new PBPs (chromosome mediated)

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2
Q

Cephalosporins

A

Beta-lactamases (Plasmid-mediated)
Decreased permeability of the drugs through variable outer membranes (chromosome mediated)
Mutant and new PBPs (chromosome mediated)

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3
Q

Carbapenems

A

Decreased permeability of the drugs through variable outer membranes (chromosome mediated)
Mutant and new PBPs (chromosome mediated)

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4
Q

Monobactams

A

Decreased permeability of the drugs through variable outer membranes (chromosome mediated)
Mutant and new PBPs (chromosome mediated)

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5
Q

Vancomycin

A

Increase wall thickness (chromosome mediated)

Amino acid substitution D-ala is replaced with D-lactate (chromosome or plasmid mediated transposon)

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6
Q

Daptomycin

A

Unknown

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7
Q

Telavancin

A

Unknown

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8
Q

Fosfomycin

A

Mutations that inactivate the non-essential glycerophosphate transporter

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9
Q

Polymyxins

A

Alteration in the cell membrane lipid polysaccharides leading to intrinsic resistance (Proteus and Serratia)

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10
Q

Tetracyclines

A

Either efflux pump that expels the drug out of the cell, thus preventing intracellular accumulation (transposon in plasmid), or bacterial proteins that prevent the binding of drug to the ribosome (transposon in chromosome or plasmid). Resistance to one drug doesn’t confer universal to all tetracyclines.

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11
Q

Glycylcyclines

A

Over-expression of efflux pumps.

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12
Q

Aminoglycosides

A
  • The oxidative transport is not present, so there is no entry to the cell (plasmid mediated) like in P. aeruginosa in case of gentamicin.
  • Ribosomal binding site mutations (chromosome mediated)
  • Modification and inactivation by enzymes like adenylases, acetylases, phosphorylases (plasmid mediated) which are drug specific, so cross resistance can’t be presumed. Amikacin is the least vulnerable to these enzymes.
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13
Q

Macrolides and Ketolides

A
  • Decreased outer membrane penetration (chromosome mediated)
  • Efflux pumps (plasmid mediated)
  • Methylation of the 23S bacterial rRNA leading to decrease affinity to the 50S ribosomal subunit in G+ve bacteria (plasmid mediated)
  • Enzyme inactivation such as phosphotransferase or esterases in G-ve bacteria (plasmid mediated)
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14
Q

Fidaxomicin

A

Unknown

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15
Q

Chloramphenicol

A

Inactivation by acetyltransferase enzyme (plasmid mediated)

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16
Q

Clindamycin

A
  • Decreased outer membrane penetration (chromosome mediated)
  • Efflux pumps (plasmid mediated)
  • Methylation of the 23S bacterial rRNA leading to decrease affinity to the 50S ribosomal subunit in G+ve bacteria (plasmid mediated)
  • Enzyme inactivation such as phosphotransferase or esterases in G-ve bacteria (plasmid mediated)
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17
Q

Quinupristin/Dalfopristin

A
  • Methylation of 23S bacterial rRNA (Quinupristin)
  • Inactivation of Dalfopristin by acetyltransferase enzyme (plasmid mediated)
  • Efflux pumps
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18
Q

Linezolid

A

Reduced binding at the target site (S. aureus and Enterococcus spp.)

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19
Q

Fluoroquinolones

A
  • Decreased drug intracellular accumulation by decrease the number of porins (chromosome mediated) or by efflux pumps (plasmid mediated)
  • Mutant topoisomerase IV and DNA gyrase (chromosome mediated)
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20
Q

Sulfonamides

A
  • Altered dihydropteroate synthase or dihydrofolate reductase (chromosome mediated)
  • Decreased cellular permeability
  • Enhanced production of the natural substrate PABA
  • Also bacteria that can obtain folate from their environment are naturally resistant
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21
Q

Trimethoprim and pyrimethamine

A
  • Altered dihydrofolate reductase

- Efflux pumpms

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22
Q

Methenamine

A

Unknown

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23
Q

Nitrofurantoin

A

Inhibition of nitrofuran reductase that converts the drug to its highly reactive form (chromosome or plasmid mediated)

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24
Q

Isoniazid

A
  • Mutation or deletion of KatG leading to loss of catalse-peroxidase enzyme which is required to activate the drug
  • Varying mutations of the acyl carrier proteins
  • Over-expression of the target enzyme InhA.
  • All are chromosome mediated and cross-resistance may occur with Ethionamide
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25
Q

Rifamycins

A

Mutant RNA polymerase (chromosome mediated)

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26
Q

Pyrazinamide

A

Lack of pyrazinamidase enzyme

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27
Q

Ethambutol

A

Mutation of arabinosyl transferase gene (chromosome mediated)

28
Q

Para-aminosalicylic acid (4-Aminosalicylic acid)

A

Unknown

29
Q

Capreomycin and Viomycin

A

Unknown

30
Q

Cycloserine

A

Unknown

31
Q

Ethionamide

A

Unknown

32
Q

Dapsone

A

Unknown

33
Q

Clofazimine

A

Unknown

34
Q

Bedaquiline

A

Unknown

35
Q

Polyenes

A

Decreased ergosterol content of the fungal membrane

36
Q

Flucytosine

A

Decreased levels of any of the enzymes in the conversion of 5-fluorouracil and beyond or increased synthesis of cytosine can develop during therapy

37
Q

Azoles

A
  • Mutations in the C-14 alpha-demethylase gene that lead to decreased azole binding
  • Efflux pumps
38
Q

Echinocandins

A
  • Alteration of glucan synthase

- Efflux pumps

39
Q

Squalene epoxidase Inhibitors

A

Unknown

40
Q

Griseofulvin

A

Unknown

41
Q

Ciclopirox

A

Unknown

42
Q

Nitroimidazoles

A

Unknown

43
Q

Aminoquinolines

A

Unknown

44
Q

Dehydroemetine

A

Unknown

45
Q

Artemisinin

A

Unknown

46
Q

Pentamidine

A

Unknown

47
Q

Suramin

A

Unknown

48
Q

Melarsoprol

A

Unknown

49
Q

Eflornithine

A

Unknown

50
Q

Nifurtimox

A

Unknown

51
Q

Sodium stibogluconate

A

Unknown

52
Q

Miltefosine

A

Unknown

53
Q

Atovaquone-proguanil

A

Unknown

54
Q

Pyrantel Pamoate

A

Unknown

55
Q

Ivermectin

A

Unknown

56
Q

Diethylcarbamazine

A

Unknown

57
Q

Praziquantel

A

Unknown

58
Q

Niclosamide

A

Unknown

59
Q

Neuroaminidase Inhibitors

A

Mutations in neuraminidase enzyme

60
Q

Adamantane antivirals

A

Change in one amino acid of the M2 matrix protein

61
Q

Nucleotide analogs

A

Unknown or altered or deficient thymidine kinase and DNA polymerases in the case of Acyclovir

62
Q

Protease Inhibitors

A

Accumulation of stepwise mutations of the protease gene (initial mutations result in decreased ability of virus to replicate, but as the mutations accumulate virions with high levels of resistance emerge)

63
Q

Nucleoside or Nucleotide Reverse Transcriptase Inhibitors (NTRIs)

A

Mutation in the viral RT codon 184, which confers a high degree of resistance to Lamivudine and Emtricitabin, but restores sensitivity to Zidovudine and Tenofovir.
Concomitant use of agents with the same analog target is contraindicted

64
Q

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

A

Mutations in the HIV-1 RT enzyme

65
Q

Entry Inhibitors

A

Unknown

66
Q

Integrase Inhibitors

A

Single point mutations within integrase gene. Dolutegravir has limited cross-resistance with other integrase inhibitors

67
Q

Interferons

A

Unknown

Chemotherapy (4 decks)

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