Sulfanamide, Trimethoprim, Quinolones

Question 1

Antifolate drugs

Answer 1

Sulfonamides: inhibit the synthesis of dihydrofolate
Trimethoprim: inhibit the synthesis of tetrahydrofolate

Question 2

Sulfonamides

Answer 2

Bacteristatic at lower (systemic) concentrations
Bactericidal at higher (urinary) concentrations
Efficacy is influenced by pABA analogs and local infection
overcome by excess pABA
local anesthetics, e.g. procaine (pABA esters)
presence of pus & products of tissue breakdown

Question 3

Clinical Uses of Sulfonamides (alone)

Answer 3

First choice
Prophylaxis of burn infections -silver sulfadiazine
Inflammatory disorders of the G.I.T (ulcerative colitis, regional enteritis) -Salfasalazine
Second-line
Respiratory infections: infections with Nocardia
First, uncomplicated urinary tract infections (low resistance areas, susceptible strains)

Question 4

Trimethoprim

Answer 4

Specific inhibition of bacterial dihydrofolate reductase
Acts synergistically with sulfonamides
best if organism is susceptible to both drugs
Used in combination with sulfamethoxazole in U.S.
(Co-trimoxazole), 1/10
Weak base, reaches high concs. in acidic fluids
(prostatic tissues/vaginal fluids)
Broad antibacterial spectrum

Question 5

Indications for Co-trimoxazole Use

Answer 5

First choice
Urinary tract infections. Acute, chronic, recurrent
Chronic bacterial prostatitis
Pneumocystis carinii pneumonia in AIDS patients

Question 6

Adverse effects of Trimethoprim

Answer 6

Potentiate sulfonamide toxicity
Folate antagonism
leukopenia, megaloblastic anemia, cytopenia
generally only a problem in folate deficiency
contraindicated in nursing mothers, infants < 2 months

Question 7

Resistance to Co-trimoxazole

Answer 7

Recent increase in resistant strains of H. influenzae and coliform bacteria
altered form of DHFR
bypass DHFR

Question 8

Fluoroquinolones

Answer 8

Inhibit bacterial DNA gyrase/topoisomerase II
Inhibit DNA synthesis
Bactericidal
After-drug effect
Active against most aerobic Gram-negative bacteria

Question 9

Ciprofloxacin (Cipro)

Answer 9

Inhalational anthrax (post-exposure)
caused by Bacillus anthracis spores
Others: Doxycycline and penicillin

Question 10

Adverse effects of fluoroquinolones

Answer 10

Well tolerated
Occasional headache, dizziness, insomnia, skin rashes
Can cause tendon rupture: no strenuous exercise
Not recommended for pregnant women, or children <18 years, due to potential for cartilage malformations

Question 11

Drug interactions of fluoroquinolones

Answer 11

P450 inhibition
potentiation of theophylline toxicity due to inhibition of CYP1A2
(Clinically important)
- Caffeine
NSAIDs
Divalent , trivalent cations, and drugs containing them