PHARMACOLOGY OF SULFONAMIDES

History
Sulfonamide drugs were the first antimicrobial drugs, and paved the way for the antibiotic revolution in medicine. The first sulfonamide was trade named Prontosil, which is a prodrug Prontosil,

Sulfonamides

Effective against a broad range of microorganisms Block specific step in biosynthetic pathway of folic acid Interfere with PABA and folic acid formation, thereby destroying bacteria

Classification of Sulfonamides Oral, absorbable

Short-acting Medium-acting Long-acting

Oral, nonabsorbable; Topical;

Oral, absorbable
Short-acting;4Short-acting;4-8hr
Sulfadiazine

Medium-acting;8Medium-acting;8-12hr
Sulfamethaxazole

LongLong-acting;~7hr
Sulfadoxine,Sulmethopyrazine

Oral, nonabsorbable; Sulfasalazine, Topical; Sodium sulfacetamide ophthalmic solution or ointment, Mafenide acetate, SML; Silver sulfadiazine, SD-Ag

Mechanism of action
Bacteriostatic action Prevent synthesis of folic acid required for synthesis of purines and nucleic acid Does not affect human cells or certain bacteriathey bacteria can use preformed folic acid

Antimicrobial Spectrum of Sulfa Drugs

Sulfonamides have broad spectrum activity against both gram-positive and gramgramgram-negative bacteria

Bacterial Resistance to Sulfonamides

Resistance to sulfonamide antibiotics is also common, and they are frequently used in combination with trimethoprim; a combination that blocks two steps in folic acid metabolism and thus helps prevent the emergence of strains of bacteria resistant to sulfa drugs.

Pharmacokinetics
Oral administration, absorbed well, Distributed widely to tissues and body fluids, including CNS and cerebrospinal fluid, placenta, and fetus; 20-90% protein binding rate; 20Acetylated or glucuronidated in the liver,

Sulfonamides and inactive metabolites are excreted into the urine, they are more soluble at alkaline than at acid pH. In renal pH. failure patient, drug dose must be reduced.

Clinical uses of Sulfonamides

SD+TMP
a. Treatment of urinary tract infections b. Respiratory tract infections, sinusitis, bronchitis, pneumonia, otitis media, and dysentery,
SMZ+TMP

FirstFirst-line therapy for treatment of acute toxoplasmosis

Sulfadoxine+Tmp
Used as a second-line agent in treatment for malaria.

Sulfasalazine
widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease.

Mafenide acetate
Prevent bacterial colonization and infection of burn wounds,

Silver sulfadiazine
For prevention of infection of burn wounds

Adverse effects of Sulfonamides

Allergenic reactions All sulfonamides and their derivatives, including carbonic anhydrase inhibitors, thiazides, furosemide, bumetanide, torsemide, diazoxide, and the sulfonylurea hypoglycemic agents are crosscross- allergnic.

1. Urinary tract disturbances

Sulfonamides may precipitate in urine, especially at neutral or acid pH, producing crystalluria, hemturia, or even obstruction. SD & SMZ, when in large doses, fluid intake is poor, can cause crystalluria. Sodium bicarbonate to alkalinize the urine, adequate fluids,

2. Hematopoietic disturbances
Hemolytic or aplastic anemia, granulocytopenia, thrombocytopenia, or leukemoid reactions. Provoke hemolytic reactions in patients whose red cells are deficient in glucoseglucose6-phosphate dehydrogenase.

The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea. StevensStevens-Johnson syndrome, is a particularly serious and potentially fatal type of skin and mucous membrane eruption associated with sulfonamide use.
Patient Suffering from StevensJohnson syndrome

Sulfonamides Side Effects :

Rash Nausea Drug fever Vomiting Jaundice Blood complications Kidney damage

References
Beers Mark H., and Robert Berkow, eds. The Merck Manual, 2nd ed. home edition. West Manual, Point, PA: Merck & Co., 2004. Marx, John A. Rosen's Emergency Medicine: Concepts andClinical Practice, 5th ed. St. Louis, Practice, MO: Mosby & Co, 2002. Mcevoy, Gerald K., et al. AHFS Drug Information 2004. Bethesda, MD: American Society of Bethesda, Healthsystems Pharmacists, 2004.