Antifolates

Question 1

Sulfonamide activity

Answer 1

STATIC

Question 2

Sulfonamide MoA

Answer 2

they are structural analogs of p-aminobenzoic acid, so they inhibit the synthesis of tetrahydrofolic acid specifically by inhibiting dihydropteroate and preventing PABA conversion to dihydrofolic acid in DNA synthesis

Question 3

Sulfonamide toxicity

Answer 3

hypersensitivity reaction, hemolytic anemia, aplastic anemia, agranulocytosis (immunosuppresion), crystalluria, neurotoxicity

Question 4

Why do sulfonamides cause neurotoxicity?

Answer 4

they inhibit the enzyme sepiapterin reductase, which is involved in biosynthesis of neurotransmitters

Question 5

How are sulfonamides distributed in the body?

Answer 5

well-distributed including CSF and placenta, readily absorbed from GIT

Question 6

What are the mechanisms of resistance against sulfonamides?

Answer 6

expression of altered enzyme dihydropteroate synthase, increase in PABA production, development of alternate pathway for DNA synthesis, decrease in bacterial permeability

Question 7

What is Bactrim?

Answer 7

sulfamethoxazole and trimethoprim

Question 8

What is the MoA of Bactrim?

Answer 8

inhibition of DHFR (trimethoprim) therefore inhibiting the conversion of dihydrofolic acid to tetrahydrofolic acid

Question 9

Bactrim toxicity

Answer 9

leukopenia, megaloblastosis, thrombocytopenia