Sulfa And Trimethoprim Antibacterials

Question 0

Antibacterial spectrum of sulfonamides

Answer 0

Gram(+) and gram(-)
Atypical bacteria
Nocardia=>pneumonia
Chlamydia trachomatis=> conjunctivitis
E. Coli=>cystitis
Bacteriostatic
Poor activity against anaerobes (b/c active transport is needed to take up sulfonamides)

Question 1

MOA of sulfonamides

Answer 1

1. Inhibition of dihydropteroate synthetase–>competitive inhibition with PABA. Shuts down THF synthesis
2. Attachment to petridine ring leading to false metabolite

Question 2

Sulfonamides ADRs

Answer 2

Rash, photosensitivity, drug fever
Steven Johnson's syndrome
Hematopoietic disturbances (blood disorders)
-especially in G6PD deficient pts.
Kernicterus In newborns

Question 3

Sulfonamide bacterial resistance mechanisms

Answer 3

Common

1. Alteration in enzyme dihydropteroate synthetase
2. Overproduction of PABA (PABA will outcompete sulfonamide)

Question 4

Trimethoprim MOA

Answer 4

Inhibits dihydrofolate reductase (DHFR): enzyme converts folic acid to tetrahydrofolate
Selective toxicity b/c human enzyme requires much higher concentrations of drug to be inhibited

Question 5

Trimethoprim bacterial resistance mechanisms

Answer 5

Similar to sulfonamides
Alteration of target:
Dihydropteroate synthase (sulfonamide combination)
Dihydrofolate reductase
Overproduction of PABA

Question 6

Bactrim, Septra

Answer 6

Trimethoprim-sulfamethoxazole (1:5)
Used primarily for treatment of UTI
Combination is synergistic
Minimizes bacterial resistance
ADR: hyperkalemia

Question 7

Nitrofurantoin

Answer 7

Furan ring
Lower UTI infections
Resistance not common b/c MOA is not well defined
ADEs: nausea (take with food or milk. Macrocrystalline product decreases nausea bc it is slower to dissolve), pulmonary rxns, peripheral neuropathy, hemolytic anemia -G6PD