Sulfonamides

Question 1

What is the mechanism of action of sulfonamide antibiotics?

Answer 1

Sulfonamides are PABA analogs that competitively inhibit dihydropteroate synthase, blocking folate synthesis in bacteria (bacteriostatic when used alone).

Question 2

Which sulfonamide inhibits Dihydrofolate reductase?

Answer 2

Trimethoprim

Question 3

What unique sulfonamide is used in the treatment for leprosy?

Answer 3

Dapsone

Question 4

Describe the antimicrobial spectrum of sulfonamides.

Answer 4

Broad spectrum but bacteriostatic:
* Gram-positive (including Nocardia, some MRSA when combined with trimethoprim)
* Many Gram-negatives (E. coli, Shigella, Salmonella)
* Often used in combination with trimethoprim (TMP-SMX) to enhance bactericidal activity and cover Pneumocystis jirovecii, Toxoplasma, and other opportunistic infections.

Question 5

What are common mechanisms of resistance to sulfonamides?

Answer 5

Bacteria may develop resistance by:
* Altering the dihydropteroate synthase enzyme (mutation)
* Increasing production of PABA (outcompeting the drug)
* Reducing uptake/increasing efflux of the drug.

Question 6

Outline key pharmacokinetic features of sulfonamides.

Answer 6

Most sulfonamides are:
* Well absorbed orally
* Distribute widely (including CNS and placenta)
* Metabolized in the liver (acetylation)
* Excreted by the kidneys
* Can precipitate in urine, especially if acidic, causing crystalluria
* Highly protein-bound (can displace other drugs from albumin).

Question 7

What major drug interactions occur with sulfonamides?

Answer 7

Sulfonamides can:
* Displace drugs from albumin (e.g., warfarin, methotrexate, bilirubin)
* Increase warfarin’s anticoagulation effect
* Raise free bilirubin (risk of kernicterus in infants)
* Inhibit CYP2C9, which can increase levels of warfarin and phenytoin
* Should avoid co-administration with other folate antagonists (additive bone marrow suppression).

Question 8

What are clinical indications for sulfonamide use?

Answer 8

Sulfamethoxazole is typically used with trimethoprim (TMP-SMX). Indications include:
* UTIs (common empiric therapy for cystitis)
* Pneumocystis pneumonia (treatment and prophylaxis in immunocompromised patients)
* Toxoplasmosis (with pyrimethamine)
* Sulfadiazine + pyrimethamine is first-line for toxoplasmosis
* Nocardia infections
* Some MRSA skin infections
* Topical sulfonamides (sulfacetamide) for conjunctivitis
* Silver sulfadiazine for burn wound infections (prevents infection).

Question 9

What are important contraindications or cautions for sulfonamides?

Answer 9

Avoid in:
* Late pregnancy and neonates due to risk of kernicterus (bilirubin displacement)
* Patients with sulfa allergy (can cause serious rash or Stevens-Johnson syndrome)
* Use with caution in G6PD deficiency, as sulfonamides can trigger hemolytic anemia
* Dose reduction may be needed in renal impairment (to prevent crystalluria).

Question 10

List major adverse effects of sulfonamides.

Answer 10

Major adverse effects include:
* Hypersensitivity reactions (rash, fever, urticaria; can progress to Stevens-Johnson syndrome)
* Hemolytic anemia in G6PD-deficient patients
* Nephrotoxicity (crystalluria, interstitial nephritis)
* Hyperkalemia from ENAC channel inhibition
* Photosensitivity
* Kernicterus in infants (bilirubin displacement)
* Trimethoprim-sulfa can cause marrow suppression (megaloblastic anemia, leukopenia) due to folate antagonism.

Question 11

What is a high-yield mnemonic related to sulfonamides?

Answer 11

Remember common sulfa-containing drugs and allergy cross-reaction:
* “Sulfa Pills Frequently Cause Terrible Allergy Symptoms” (Sulfonamides, Probenecid, Furosemide, Celecoxib, Thiazides, Acetazolamide, Sulfonylureas)
* Also “Steven Johnson has sulfa allergies” to recall SJS risk.