Sulfonamides hypersensitivity

Local side effects include burning, stinging, itching, foreign body sensation, dry eyes, and conjunctivitis. Brinzolamide may have a lower incidence of these side effects since the drug is in a neutral pH solution. Dorzolamide has been reported to cause irreversible corneal decompensation. Taste abnormalities have been reported with each agent. Both topical carbonic anhydrase inhibitors are sulfonamides and are contraindicated in patients with history of sulfonamide hypersensitivity.10,13... 

Silver sulfadiazine, a sulfonamide, is used for the management of infected burns. The occurrence of sulfonamide hypersensitivity is a serious risk though and this agent should be reserved for selected cases. Its activity is probably based on the bactericidal action of silver which is released but absorbed only to a negligible extend. The sulfonamide is well absorbed and appreciable blood levels are reached when large areas are treated. 

Sulfonamide-like allergic adverse reactions Concerns that COX-2 inhibitors may be associated with an increased risk of allergic reactions in patients with a history of sulfonamide hypersensitivity arise from the molecular structures of these compounds (SEDA-24,119) (138). 

Most of the cutaneous adverse reactions to sulfonamides are associated with increased in vitro reactivity to sulfonamide metabolites, such as unstable hydroxyl-amines (160,161). In some cases glutathione deficiency has been proposed as a major mechanism. This seems to be important in patients with AIDS, in whom glutathione deficiency is frequent, and in whom skin rashes are much more common than in other patients (160,162). A predominance of slow acetylator phenotype has also been observed among patients with sulfonamide hypersensitivity reactions, and an association with the phenotypes HLA-A29, B-12, and DR-7 in patients with bullous cutaneous reactions (161,163-165). 

No diagnostic tests are available to confirm sulfonamide hypersensitivity, and while avoidance of the drug is generally appropriate when a previous hypersensitivity reaction is suspected, desensitization protocols are available for use in HIV patients in whom Pneumocystis proved pneumonia prophylaxis or treatment is indicated (193). 

Rieder MJ, Shear NH, Kanee A, Tang BK, Spielberg SP. Prominence of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions. Clin Pharmacol Ther 1991 49(1) 13-17. 

Sulfacetamide is the N1-acetyl-substituted derivative o/sulfanilamide. Its aqueous solubility is 90 times that of sulfadiazine. This drug (isopto-cetamide, others) is employed extensively for ophthalmic infections. Very high aqueous concentrations are not irritating to the eye and are effective against susceptible microorganisms. The drug penetrates readily into ocular fluids and tissues. Sensitivity reactions to sulfacetamide are rare, but it should not be used in patients with known sulfonamide hypersensitivity. 

N-acetyltransferases (NATs) that have been implicated with the emergence of sulfonamides hypersensitivity and the toxicity observed in some cases of isoniazid, procainamide, and hydralazine administration [27]. 

Rieder MJ, Uetrecht J, Shear NH, Cannon M, Miller M, Spielberg SP (1989) Diagnosis of sulfonamide hypersensitivity reactions by in-vitro rechallenge with hydroxylamine metabolites. Ann Intern Med 110 286-289... 

The authors noted that bosentan is related to the sulfonamides this may therefore have been a sulfonamide hypersensitivity reaction. 

Immunologic Ocular administration of dorzolamide and timolol (doses not stated) in a woman with glaucoma led to the development of a disseminated eruption associated with severe thrombocytopenia [4 ]. A skin biopsy showed hyperkeratosis, acanthosis, and perivascular and periadnexal infiltrates without vasculitis. The skin reaction resolved after withdrawal of dorzolamide and treatment with an antihistamine, but the thrombocytopenia persisted. Subsequent treatment with dapsone led to a recurrence of the skin changes this pattern is consistent with sulfonamide hypersensitivity syndrome [SEDA-30, 252]. 

Blood dyscrasias are quite uncommon, but if they occur may be serious enough to cause discontinuance of the therapy. Both topical and systemic adrninistration of sulfas can cause hypersensitivity reactions, such as urticaria, exfoHative dermatitis, photosensiti2ation, erythema nodosum, and in its most severe form, erythema multiformexudativum. (Stevens-Johnson syndrome). In general, however, use of sulfonamide therapy is considered relatively safe. 

Loop diuretics are contraindicated in patients with known hypersensitivity to the loop diuretics or to the sulfonamides, severe electrolyte imbalances, hepatic coma, or anuria, and in infants (ethacrynic acid). 

The antibiotic and sulfonamide ophthalmics are contraindicated in patients with a hypersensitivity to the drug or any component of the drug. These dru are also contraindicated in patients with epithelial herpes simplex keratitis, varicella, mycobacterial infection of the eye, and fungal diseases of the eye There are no significant precautions or interactions when the dru are administered as directed by the primary health care provider. 

AM1241 (360) exhibited high affinity and selectivity for CB2 [it (CBi) = 280 nM, (CB2) = 3.4 nM]. (360) Dose dependently inhibited experimental neuropathic pain in a spinal nerve ligation-induced tactile and thermal hypersensitivity model [224]. Other indole derivatives bearing sulfonamide moieties on the side chain, such as compound (361), were disclosed [225]. Though 67 derivatives including pyridyl and other heteroaromatics instead of the indole core were listed, no specific biological data were shown. 

Sulfasalazine is associated with various adverse effects, most of which are thought to be due to the sulfapyridine component. Common adverse effects that may be dose related include headache, dyspepsia, nausea, vomiting, and fatigue.19 Idiosyncratic effects include bone marrow suppression, reduction in sperm counts in males, hepatitis, and pulmonitis. Hypersensitivity reactions may occur in patients allergic to sulfonamide-containing medications. 

The most common side effects include somnolence, dizziness, anorexia, headache, nausea, word-finding difficulties, oligohidrosis, modest weight loss, and irritability. Symptomatic kidney stones may occur in 2.6% of patients. Hypersensitivity reactions may occur in 0.02% of patients, and it should be used with caution if at all in patients with a history of allergy to sulfonamides. Monitoring of renal function may be advisable in some patients. 

Anuria renal decompensation hypersensitivity to thiazides or related diuretics or sulfonamide-derived drugs hepatic coma or precoma (metolazone). 

Hypersensitivity reactions Hypersensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma cross-sensitivity with sulfonamides may also occur. Refer to Management of Acute Hypersensitivity Reactions. 

Thrombocytopenia Because there have been rare spontaneous reports of thrombocytopenia with bumetanide, observe regularly for possible occurrence. Hypersensitivity reactions Patients with known sulfonamide sensitivity may show allergic reactions to furosemide, torsemide, or bumetanide. Bumetanide use following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity. Refer to Management of Acute Hypersensitivity Reactions. 

Intestinal or urinary obstruction porphyria, hypersensitivity to sulfasalazine, its metabolites, salicylates, or sulfonamides. 

Hypersensitivity to sulfonamides or chemically related drugs (eg, sulfonylureas, thiazide and loop diuretics, carbonic anhydrase inhibitors, sunscreens with PABA, local anesthetics) pregnancy at term lactation infants less than 2 months of age (except in congenital toxoplasmosis as adjunct with pyrimethamine) porphyria salicylate hypersensitivity. 

Severe reactions Severe reactions including deaths caused by sulfonamides have been associated with hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, and renal and hepatic damage. Irreversible neuromuscular and CNS changes and fibrosing alveolitis may occur. 

Hematologic effects Sulfonamide-associated deaths, although rare, have occurred from hypersensitivity of the respiratory tract, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. 

The use of the long-acting sulfonamides such as sulfadimethoxine and sulfadoxine is limited because of a high rate of hypersensitivity reactions. Sulfadoxine in combination with pyrimethamine is indicated for chloroquine-resistant falciparum malaria. 

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