L30 - Drugs

Question 1

Name the 2 drugs that block folate synthesis

Answer 1

Sulfonamides
Trimethoprim
TMP-SMX combo

Question 2

What enzyme do sulfonamides target?

Answer 2

Dihydro-pteroate synthetase

We don’t have this enzyme so no side-effects to humans in taking this

Question 3

What enzymes does trimethoprim target?

Answer 3

Dihydrofolate reductase

Drug has MUCH higher affinity for the bacterial version of this enzyme - small side effects for humans

Question 4

Sulfonamides are rarely used alone. What are they given with? Why?

Answer 4

Trimethoprim + sulfamethoxazole (TMP-SMX)

• Enhanced activity via synergy
• Broad spectrum bactericidal action
• Less resistance

Question 5

TMP-SMX use

Answer 5

Gram - 
S. aureus (g+)
Some protozoa & fungi
Pseudo & enterococci resistant
* Urinary, respiratory, GI infections*

Question 6

How are folate antagonists given

Answer 6

Oral/IV

Question 7

What are the adverse effects for folate antagonists

Answer 7

Rash, GI = common
Severe:
- SJS
- Toxic epidermal necrolysis 
- Amenias and thrombocytopenia

Question 8

What can happen with TMP-SMX during pregnancy?

Answer 8

Kernicterus = high bilirubin

Brain dysfxn in the baby

Question 9

Trimethoprim resistance

Answer 9

Plasmid w/ dhfr gene

Transposon (Tn7) of integrons

Question 10

Sulfonamide resistance

Answer 10

Plasmid that made TMP resistance/changes coding of dihydropteroate synthetase
Chromosomal mutation

Question 11

What are the 3 DNA inhibitors

Answer 11

Quinolones
Furoquinolones
Nitrofurantoin

Question 12

Quinolones mechanism

Answer 12

Double strand breaks to stabalizes topo-DNA complex
No DNA replication or RNA transcription
Chromosome fragmentation –> bactericidal (!)

Question 13

What are quinolones used against

Answer 13

Gram - by inhibiting topo2
Gram + by inhibiting topo4
Atypicals & mycobacteria

Question 14

How are quinolones given?

Answer 14

Oral

BUT poor absorption w/ divalent cations

Question 15

Drug primarily targets topo2 and has good [ ] in urine. Not gets vs Step

Answer 15

Ciprofloxacin

Question 16

Drug primarily targets topo4 and good vs Step

Answer 16

Levofloxacin

Question 17

Quniolone that has strong g + and anaerobic activity

Answer 17

Moxifloxacin

Question 18

What causes fluroquinolone resistance

Answer 18

gyrA or parC mutations

Efflux pumps

Question 19

Quinolone adverse effects

Answer 19

Prolonged OT

Tendon rupture

Question 20

What quinolone are you using to treat UTIs

Answer 20

Nitrofurantoin
Good against gram-/+ uropathogens
PO - poor serum but good urine [ ]
Might see nausea & pulm fibrosis

Question 21

What are the 2 RNA inhibitors?

Answer 21

Rifamycins

Fidaxomicin

Question 22

Rifamycin mechanism

Answer 22

Binds B subunit of RNA polymerase
X transcription
BacterioSTATIC

Question 23

Rifamycin metabolism. What are the 3 forms of rifamycin?

Answer 23

Cp450 3A4 metabolism
Rifampin - induces this enzymes
Rifabutin
Rifaximin - not absorbed so for GI infections

Question 24

Rifamycin use

Answer 24

In combos!
Prophylasis of N.meningitidis & S.aureus
GI as rifaximin - traveler’s diarrhea

Question 25

Rifamycin adverse effect

Answer 25

Hepatitis

Question 26

Fidaxomicin mechanism

Answer 26

No open DNA complex –> X RNA polymerase

Non-absorbable!

Question 27

Fidaxomicin use

Answer 27

C.diff!

Question 28

Rifamycin and fidaxomicin is given…

Answer 28

PO