Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Chapter 87 Sulfonamides and Trimethoprim

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 Sulfonamides and Trimethoprim  Broad-spectrum antibiotics  Both have closely related mechanisms  Suppress bacterial growth by inhibiting tetrahydrofolic acid

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Sulfonamides  First drugs available for systemic treatment of bacterial infections  More effective and less toxic drugs now available  Inhibit the synthesis of folic acid (folate)  Mammalian cells do not manufacture their own folate (not affected like bacteria are affected)  Primary use now – for urinary tract infections  Other uses: nocardiosis, Chlamydia trachomatis, conjunction therapy for toxoplasmosis/malaria, ulcerative colitis

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 Sulfonamides  Adverse effects  Hypersensitivity reactions – Stevens-Johnson syndrome  Hematologic effects  Kernicterus  Renal damage from crystalluria  Drug interactions  Metabolism-related interactions  Allergy-inducing drugs

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.5 Fig Structural relationships among sulfonamides, PABA, and folic acid.

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.6 Fig Sites of action of sulfonamides and trimethoprim. Sulfonamides and trimethoprim inhibit sequential steps in the synthesis of tetrahydrofolic acid (FAH 4 ). In the absence of FAH 4, bacteria are unable to synthesize DNA, RNA, and proteins.

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.7 Trimethoprim (Proloprim and Trimpex)  Inhibits dihydrofolate reductase  Uses  Acute and uncomplicated urinary tract infections Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter, coagulase-negative Staphylococcus Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter, coagulase-negative Staphylococcus  Adverse effects  Hematologic effects  Use in pregnancy and lactation

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.8 Trimethoprim-Sulfamethoxazole  The trimethoprim-sulfamethoxazole (TMP- SMZ) combo inhibits sequential steps in bacterial folic acid synthesis, making it much more powerful than TMP or SMZ alone.  Therapeutic uses  Urinary tract infection, otitis media, bronchitis, Shigellosis, pneumonia by Pneumocystis jiroveci, Pneumocystis pneumoniae, and GI infections

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.9 Trimethoprim-Sulfamethoxazole  Adverse effects  Gastrointestinal Nausea and vomiting Nausea and vomiting  Rash  Hypersensitivity reactions (Stevens-Johnson syndrome) Blood dyscrasias Blood dyscrasias Kernicterus Kernicterus Renal damage – crystalluria Renal damage – crystalluria