Antifolate Drugs

Question 1

What two activities does sulfamethoxazole has?

Answer 1

antibacterial and antimalarial activity

Question 2

What is the mechanism of action of sulfamethoxazole?

Answer 2

Inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to an endogenous substrate para-aminobenzoic acid (PABA)

Question 3

What enzyme does sulfamethoxazole inhibit?

Answer 3

dihydropteroate synthase the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid.

Question 4

What is the target of sulfamethoxazole?

Answer 4

Bacterial Dihydropterate synthase antagonist

Question 5

What is the mechanism of action of trimethoprim?

Answer 5

Reversible inhibitor of dihydrofolate reductase

Question 6

Why is tetrahydrofolate important?

Answer 6

It is necessary for the biosynthesis of bacterial nucleus acids and proteins

Question 7

Which two drugs when given together have bactericidal activity?

Answer 7

Trimethoprim and sulfamethoxazole

Question 8

Can trimethoprin and sulfamethoxazole be administered intramuscularly and intravenously?

Answer 8

yes

Question 9

trimethoprim and sulfamethoxazole have near 100% what?

Answer 9

bioavailability

Question 10

Trimethoprim and sulfamethoxazole have almost identical what?

Answer 10

half lives (8-10 hours) and 10 hours respectively

Question 11

Concentrations of trimethoprim in most tissues and body fluids, including sputum and pleural fluids appear to be higher than in corresponding what?

Answer 11

serum levels

Question 12

Trimethoprim and sulfamethoxazole penetrate well into the…

Answer 12

middle ear fluid of patients with chronic serious otitis media, bronchoalveolar lavage fluid, skin blister fluid, levels in the kidney can be 20 fold higher than those in the serum, TMP/SMX penetrates well into the CSF of patients with normal meninges, TMP diffuses well into human vaginal fluid but not sulfamethoxazole

Question 13

What enzymes are involved in the metabolism of trimethoprim?

Answer 13

CYP2C9 and CYP3A4 and CYP1A2 contributing to a lesser extent

Question 14

Sulfamethoxazole’s metabolism is mediated mostly by …?

Answer 14

acrylamine N-acetyltransferase enzymes which are responsible for acetylation of sulfamethoxazole

Question 15

Approximately 10-20% of an ingested trimethoprim dose is metabolized, primarily in the liver, while a large portion of the remainder is excreted unchanged in the…

Answer 15

urine

Question 16

What are some adverse effects of trimethoprim/sulfamethoxazole?

Answer 16

rash, renal impairment, hyperkalemia, gastrointestinal symptoms, and hypersensitivity

Question 17

What are some hematological adverse effects caused by trimethoprim/sulfamethoxazole?

Answer 17

aplastic anemia, neutropenia, acute agranulocytosis and acute thrombocytopenia

Question 18

What are some nephrotoxic effects of trimethoprim/sulfamethoxazole?

Answer 18

increased serum creatinine levels, acute renal failure. The pathogensis of these effects includes competitive creatinine excretion, crystalluria, interstitial nephritis, and acute tubular necrosis