Antibiotics 5 - Sulfonamides and Quinolones Flashcards Preview

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Flashcards in Antibiotics 5 - Sulfonamides and Quinolones Deck (67):
1

(sulfonamide) ______ was inactive in vitro

 

But this is a prodrug of the active ________

Prontosil

 

p-aminobenzenesulfonamide

2

Sulfanilamide (pharmacologically active) is used to treat ____ infections

Vaginal candida

3

MOA of sulfonamide antibiotics

Competitively inhibits the incorporation of PABA into folic acid

 

by inhibiting the enzyme dihydropteroate synthase

4

What reaction does dihydropteroate synthase catalyze?

 

What are the following steps in this pathway?

Dihydropteroate diphosphate -> Dihydropteroic acid

 

**next steps: conversion to DHF acid -> THF acid --> methyleneTHF acid --> Thymine --> DNA

5

Sulfonamides are bioisosteres of ____

PABA

6

There is a significant difference in ____ between PABA and sulfanilamide

 

What does this mean for the drug?

Acidity  (pKa)

PABA = 6.5   Sulfanilamide = 10.4

 

This causes sulfanilamide to be 1000x more neutral as a drug

7

What two effects does attaching electron-withdrawing heteroaromatic rings to the sulfonamide nitrogen?

Increases ACIDITY = increased stability = increased potency**

This also decreases crystalluria in the urine

 

**essentially makes it more similar to the normal metabolite

8

Sulfonamides in general inhibit...

  • Gram + and -
  • Nocardia
  • Chlamydia trachomatis
  • Enterics (e.coli, kleb, salmonella, shig, enterobact)
  • some protozoa and fungi

9

Sulfamethoxazole combined with ____ is important for treatment of _______

Trimethoprim

PCP (in aids)

10

Trimethoprim inhibits _____

Dihydrofolate reductase

11

Most common sulfa

Sulfisoxazole

12

sulfisoxazole and sulfamethoxazole are mainly used to treat ________

uncomplicated UTI

13

What is triple sulfa and what does it treat?

1:1:1 mix of -benzamide, -acetamide,  -thiazole

 

Treatment of Gardnerella vaginalis

14

Sulfasalazine is a____ that is not...

 

What is the metabolism?

prodrug,  ...not absorbed well in GIT

 

**metabolized to sulfapyridine and 5-aminosalicylic acid

15

Long acting sulfonamide

Sulfadoxine

16

Sulfadoxine is used with _____ to treat _____

pyrimethamine

malaria

 

(pyrimethamine inhibits DHFR in p. falciparum)

17

Sulfadiazine is used with _____ to treat _____

pyrimethamine

Toxoplasma gondii

18

Sulfonamide derivative examples (3)

  1. Carbonic anhydrase inhibitors (acetazolamide)
  2. Thiazides (HCTZ)
  3. Hypoglycemic agents (tolbutamide)

19

Most commone AE's of sulfonamides (6)

  1. Rash
  2. Photosensitivity
  3. Drug fever
  4. Stevens-Johnson syndrome
  5. Crystalluria
  6. Hematopoietic disturbances (HA, AA, Granul, Thromb)

20

What three mutations can cause resistance to sulfonamides

Overproduction of PABA

Dihydropteroate synthase

Decrease in cell permeability

21

Bactrim composition

400mg SMX

80mg TMP

22

PK of TMP compared to SMX

absorbed 85=90%

distributed more rapidly than SMX

23

SMX distribution and clearance (description)

wide distribution

rapid clearance

 

24

Why isnt SMX as widely distributed as TMP

Differences in lipophilicity

25

Tissue ratio of SMX:TMP

1:2 to 1:5

26

Short half life sulfas

Soxazole

methizole

27

Intermediate half life sulfas

Diazine

methoxazole

28

Sulfa metabolism mechanism

VIa N-4 N-acetylation

 

(in some cases N-1 glucuronidation)

29

Toxic metabolites of sulfa

Hydroxylamine and nitroso metabolites

30

First gen Quinolones have limited ___ activity

G+

31

FIrst gen quinolones are only useful for 

lower UTIs

32

Two examples of First gen quinolones

Nalidixic Acid

Oxolinic acid

33

Second gen quinolone structure difference

Fluuorine ata C6

Heterocyclic ring (usually piperazine) at C7

34

Norfloxacin and levofloxacin shows a 40-100x poteny over nalidixic acid against...

most gram negatives incl. pseudomonas

35

Second gen quinolones have an extended activity against

G+ and mycoplasma

36

3rd and 4th gen quinolones often have _____

multiple Fluorine atoms

37

Best 3rd/4th gen for G-

Ciprofloxacin

38

Which quinolone is a last resort?

Moxi

39

topoisomerases (TI) and gyrases cleave DNA by ...

carrying out nucleophilic attack on a phosphodiester linkage

 

--> one strand is free and one is enzyme linked

40

Nucleophile used by TI/gyrase

phenolic OH group of Tyrosine

41

TI-catalyzed reaction is _____ 

 

The equilibrium tends to favor...

Reversible

 

in favor of the uncleaved DNA

42

Most common use for quinolones

UTI

43

Second and Third most common use for quinolones

Prostatitis

STD

44

Chlamydia trachomatis quinolones

ofloxacin + sparfloxacin

45

quinolone for N gonorrheae and H. ducreyi

Ciprofloxacin

46

First line  for gonorrhea

ceftriaxone

47

Fourth and Fifth use for quinolones

GI

Respiratory Tract Infections

48

Shigellosis quinolones

Nor

Cipro

O

49

Which quinolones WONT treat Bone, join, and soft tissue infections

Norfloxacin

50

____ is 50% effective as monotherapy in diabetic foot infections

Cipro

51

Quinolones that have use against intraellular bacteria

Nor

Cipro

52

Resistant organisms (to quinolones) have spontaneously occurring point utations in...

the A-subunit of DNA gyrase

 

(results in a 16-fold increase in MBC for fluoroquinolones)

53

Less common mutation for quinolone resistance

the B subunit of DNA gyrase

 

(results in a lower level of resistance)

54

Penetration of quinolone to gram negative bacteria is dependen on...

diffusion through porin channels (esp in E. coli and pseuomonas)

55

____ should be avoided when giving quinolones

Under-dosing

56

Quinolones high or low oral BA?

Wide or narrow distribution?

High oral BA

Wide distribution

57

Route of clearance for all quinolones (with one exception)

Renal and hepatic

(oxafloxacin is 95% renal)

58

Interstitial fluid concentrations __________ from 4-24 hours

Exceed serum concentrations

59

Quinolones form insoluble chelates with ______

heavy metals

60

Major inactive metabolite is the ______

glucuronide at the 3 carboxyl position

 

excreted in the urine

61

Most common AE for quinolones

N/V/D

62

Hallucinations and delirium an occur in patients who are also taking...

Theophylline

NSAID

63

Quinolones are associated wih ____ (as an AE)

peripheral neuropathy

64

Why shouldnt you give quinolones to kids?

May damage growing cartilage and cause arthropathy (reversible)

65

Lomefloxacin AE

Photosensitivity

66

Gatifloxacin AE

Hyper/Hypoglycemia in diabetic patients

67

Exception to the "dont give to kids" rule for quinolones

Pseudomonal infections in kids with CF

 

(High mortality rate, benefits>risks)