Many people are allergic to the sulfonamide moiety and experience hypersensitivity reactions characterized by an excessive immune response. Common symptoms include rashes, hives, itchy eyes, and swollen tongue or face. Some individuals can have an anaphylactic reaction.
Sulfonamides can cause nephrotoxicity via crystalluria, or crystals in the urine. Sulfonamides are acetylated in the liver and in this form are insoluble in acidic urine, causing precipitation to form crystals. This can lead to kidney damage, but can be prevented by adequate oral hydration and alkalinization of the urine.
Photosensitivity, or an increased sensation and intolerance to sunlight, is a common adverse reaction experienced by some patients on sulfonamide antibiotics.
Kernicterus is caused by elevation of bilirubin leading to accumulation in the gray matter of the central nervous system, potentially causing irreversible neurological damage. Sulfonamides can bind with albumin at the same receptor site as bilirubin, causing displacement of bilirubin and subsequently, kernicterus. Infants are particularly vulnerable to kernicterus because the glucuronidation system has not adequately matured to metabolize bilirubin.
TMP-SMX is known to increase blood concentrations of warfarin via displacement of warfarin from albumin in the plasma. This can cause unexpected increases in clotting time and uncontrolled bleeding for individuals on anticoagulation with warfarin therapy.
Sulfonamides can cause increased oxidative stress in the body and precipitate hemolytic anemia in individuals with G6PD deficiency. Glucose 6 phosphate dehydrogenase deficiency is an X linked recessive disorder characterized by a deficiency of the enzyme glucose 6 phosphate dehydrogenase (G6PD). This enzyme is involved in the pentose phosphate pathway and supplies reducing substances by converting NADP to NADPH. This NADPH is used by glutathione reductase to maintain levels of glutathione in cells, which helps protect red blood cells against oxidative damage caused by free radicals and peroxides.
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