Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

5224 > Tetrahydrofolate Synthesis Inhibitors > Flashcards

Tetrahydrofolate Synthesis Inhibitors Flashcards

1
Q

first sulonamide

A

sulfanilamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

sulfonamides first used clinically

A

1933

Penicillin discovered first, but not used clinically until the 1940’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Chemistry of sulfonamides

A
  • S linked to benzene ring

- Amino group linked to the same benzene ring in para position

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Antimicrobial activity and spectrum of sulfonamides

A
  • bacteriostatic
  • work against gram + and gram -
  • resistance is common
  • sensitive bacteria:
    strep pyogenes
    strep pneumoniae
    haemophilus influenzae
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is tetrahydrofolate

A
  • coenzyme for DNA synthesis: purine synthesis and 1C transfer rxns
  • in humans, it is a 2-step reduction and folate must be taken up in diet or from gut bacteria
  • Most bacteria synthesize their own
  • if bacteria cannot make it, they cannot replicate = bacteriostatic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MOA of sulfonamides

A
  • compete with PABA for dihydropteroate synthase

- competitive inhibition of the first step of tetrahydrofolate synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Resistance to sulfonamides

A
  1. mutated dihydropteroate synthase with decreased affinity for sulfonamides (acquired resistance)
  2. decreased permeability or active efflux of drug
  3. alternative metabolic pathway
  4. increased production of substrate (PABA) -> inactivation of drug not observed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Sulfonamide specificity

A
  • only bacteria that need to synthesize their own tetrahydrofolate are susceptible to these drugs
  • some bacteria can use preformed folic acid and are not susceptible
  • We take up folic acid from environment so we’re not susceptible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Rapidly absorbed and eliminated sulfonamides

A

PK: peak after 2-6 hours, t1/2 of 5-12 hours, gone after 1-3 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Sulfisoxazole acetyl

A

tasteless formulation for kids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Silver sulfdiazine

A

used topically to prevent burn infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are acetylated forms of sulfonamides cleared?

A
  • renally
  • drink plenty of water
    crystals can form in urinary tract (crystalluria)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Are sulfonamides used alone?

A

No, due to resistance. Used in combo to treat Nocardia infections (trimethroprim-sulfamethoxazole)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Toxicity

A
  • observed in 5% of pts
  • most common: crystalluria
  • Hypersensitivity rxns < 3%
  • anorexia, N/V (1-2%)
  • hematopoietic disorders < 1%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Trimethoprim-sulfamethoxazole

A
  • TMP-SMZ, Bactrim, Septra, Sulfatrim
  • trimethoprim inhibits THIRD step in tetrahydrofolate synthesis
  • synergistic with sulfamethoxazole
  • THREE methoxy groups
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

MOA of trimethoprim

A
  • competes with dihydrofolate for dihydrofolate reductase
  • competitive inhibition of the third step of tetrahydrofolate synthesis
  • humans use DHFR but it’s sufficiently different from bacterial
17
Q

Definition of drug-drug synergy

A

Synergy in general:
the effect of two drugs given in combo is greater than just the additive effect of the two drugs
Synergy in pharmacology:
Less than half of the concentration of both drugs is necessary to yield an effect of 100% of each separate drug

18
Q

Specificity of trimethoprim

A
  • inhibits bacterial dihydrofolate reductase much more effectively than human dihydrofolate reductase.
  • low toxicity
19
Q

Active spectrum of TMP-SMZ

A

Gram + and Gram - ; combo effective against resistant drugs.

20
Q

Ideal ratio of TMP-SMZ

A

1:20

21
Q

What is pyrimethamine-sulfadiazine used to treat

A

toxoplasma gondii infections

22
Q

What is pyrimethamine-sulfadoxine used to treat

A

plasmodium spp infections (malaria)

23
Q

Resistance to TMP-SMZ

A
  • Co-resistance is less likely than resistance to individual drugs
  • resistant version of dihydrofolate reductase encoded in plasmid easily acquired, so resistance on the rise
24
Q

What is TMP-SMZ used for

A
  • UTI
  • bacterial respiratory tract infections
  • GI infections
  • S. aureus (skin and soft tissue)
  • Pneumocystis jiroveci (fungus that causes pneumonia)
  • prophylaxis in neutropenic pts.
25
Q

Toxicity of TMP-SMZ

A
  • generally few adverse effects at appropriate dose
  • skin rxns, esp in elderly
  • N/V
  • Hypersensitivity in AIDS pts

5224 (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions