Download Chapter 16 Cholinesterase Inhibitors

Chapter 87
Sulfonamides and Trimethoprim
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Sulfonamides and Trimethoprim
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Broad-spectrum antibiotics
Both have closely related mechanisms
Suppress bacterial growth by inhibiting
tetrahydrofolic acid
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Sulfonamides
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First drugs available for systemic treatment of
bacterial infections
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Inhibit the synthesis of folic acid (folate)
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More effective and less toxic drugs now available
Mammalian cells do not manufacture their own
folate (not affected like bacteria are affected)
Primary use now – for urinary tract infections
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Other uses: nocardiosis, Chlamydia trachomatis,
conjunction therapy for toxoplasmosis/malaria,
ulcerative colitis
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Sulfonamides
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Adverse effects
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Hypersensitivity reactions – Stevens-Johnson
syndrome
Hematologic effects
Kernicterus
Renal damage from crystalluria
Drug interactions
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Metabolism-related interactions
Allergy-inducing drugs
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Fig. 87-1. Structural relationships among sulfonamides, PABA, and folic acid.
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Fig. 87-2. Sites of action of sulfonamides and trimethoprim.
Sulfonamides and trimethoprim inhibit sequential steps in the synthesis of tetrahydrofolic acid
(FAH4). In the absence of FAH4, bacteria are unable to synthesize DNA, RNA, and proteins.
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Trimethoprim (Proloprim and
Trimpex)
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Inhibits dihydrofolate reductase
Uses
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Acute and uncomplicated urinary tract infections
• Escherichia coli, Proteus mirabilis, Klebsiella
pneumoniae, Enterobacter, coagulase-negative
Staphylococcus
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Adverse effects
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Hematologic effects
Use in pregnancy and lactation
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Trimethoprim-Sulfamethoxazole
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The trimethoprim-sulfamethoxazole (TMPSMZ) combo inhibits sequential steps in
bacterial folic acid synthesis, making it much
more powerful than TMP or SMZ alone.
Therapeutic uses
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Urinary tract infection, otitis media, bronchitis,
Shigellosis, pneumonia by Pneumocystis jiroveci,
Pneumocystis pneumoniae, and GI infections
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Trimethoprim-Sulfamethoxazole
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Adverse effects
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Gastrointestinal
• Nausea and vomiting
Rash
Hypersensitivity reactions (Stevens-Johnson
syndrome)
• Blood dyscrasias
• Kernicterus
• Renal damage – crystalluria
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