drug resistance

Question 1

first line drug against TB

Answer 1

isoniazid (inhibits mycolic acid formation)

Question 2

Yersinia is treatable by

Answer 2

SCT
- streptomycins
- chloramphenicol
- tetracyclins

Question 3

resistance against antifungals - examples

Answer 3

• fluconazole (multidrug efflux pumps + change enzymes)
• rifampin (DNA-dep RNA pol can’t get into membrane)

Question 4

resistance against antivirals - examples

Answer 4

• aciclovir
• zidovudine/AZT
• saquinavir

all via enzyme mutation

Question 5

resistance against anti parasitic agents - examples

Answer 5

chloroquine (exclusion through ATP-dep P-glycoprotein or mutated CRT, active transporter)

Question 6

three ways of bacterial resistance to drugs

Answer 6

1. enzymatic inactivation
2. change targets
3. influx/efflux pumps

Question 7

bacterial resistance: enzymatic inactivation (give examples of mechanism)

Answer 7

• beta-lactamases by E. coli, S. pneumoniae, H. influenzae, N. gonorrhoea
• aminoglycoside & streptogramin

Question 8

bacterial resistance: change targets (give examples of mechanism)

Answer 8

1. methicillin: S. aureus (mecA and fem G5 > GAS), also S. pneumoniae
2. vancomycin: E. faecalis (VanH, VanA, VanX, VanS, VanR - switch D-Ala-D-Lac)
3. macrolides: pneumococci (A2058 methylation in 28S rRNA @ 50S ribosomal subunit)

Question 9

bacterial resistance: influx/efflux pumps (give examples of mechanism)

Answer 9

INFLUX: P. aeruginosa, aminoglycosides (hydrophilic) so less porins and oligopeptide transporters
EFFLUX: usually secondary active (couple H+/Na+ antiporters) e.g. TetA tetracyclins

Question 10

how is methicillin resistant to beta lactamases?

Answer 10

2,6-dimethozybenzoyl substitution on 6-amino penicillin scaffold