Antifolate drugs

Question 1

Sulfonamides/sulfamethoxide

MoA

Answer 1

inhibits dihydropteroate synthesis, a precursor to dihydrofolate

Question 2

Trimethoprim MoA

Answer 2

Inhibits dihydrofolate synthesis

Question 3

Spectrum and indications

Answer 3

Spectrum: Broad spectrum G+ and G-

Indications: 
Pneumocystis jiroveci/carnii
Toxoplasma gondii, 
Nocardia
Leishmania
some p Falciparums. 

Shigella, Salmonella

UTIs

Question 4

Kinetics

Answer 4

Good oral absorption, can be given Oral or Parenteral.
Very wide distribution:
- enters CNS, Urinary tract, crosses placenta (contrad in preggos)

Question 5

Why are they always in combination?

Answer 5

To prevent rapid resistance development in trimethoprim monotherapy

Question 6

List some sulfonamide drugs

Answer 6

Topical agents:
Sulfacetamide
Sulfadimidine
Sulfadiazine
Sulfasalazine

Question 7

Adverse reactions to Sulfa+Trimeth

Answer 7

Allergic reactions, rashes, potential SJS
GI effects
Photosensitivity

Nephrotoxicity due to crystal precipitation, hydration is essential

Hematotoxicity (antifolate-folate def. pancytopenia)
Hemolysis in G6PDH def.

Inhibits bilirubin excretion in newborns, can cause CNS bilirubin toxicity aka kernicterus