Sulfonamides thrombocytopenia with

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. 

Serious adverse effects are rare except in AIDS patients. TMP-SMX can cause the same adverse effects as those associated with sulfonamide administration, including skin rashes, central nervous system (CNS) disturbances, and blood dyscrasias. Blood dyscrasias, hepatotoxicity, and skin rashes are particularly common in patients with AIDS. Most of the adverse effects of this combination are due to the sulfamethoxazole component. Trimethoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline foUc acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia. 

The hematopoietic toxicity includes agranulocytosis, thrombocytopenia and rarely aplastic anaemia and in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, sulfonamides may cause intravascular haemolysis. 

The thiazides are sulfonamides and share cross-reactivity with other members of this chemical group. Photosensitivity or generalized dermatitis occurs rarely. Serious allergic reactions are extremely rare but do include hemolytic anemia, thrombocytopenia, and acute necrotizing pancreatitis. 

Sulfonamides can cause hemolytic or aplastic anemia, granulocytopenia, thrombocytopenia, or leukemoid reactions. Sulfonamides may provoke hemolytic reactions in patients with glucose-6-phosphate dehydrogenase deficiency. Sulfonamides taken near the end of pregnancy increase the risk of kernicterus in newborns. 

Sulfonamides have adverse effects on all bone marrow-derived cell lines. The resulting disturbances include hemolytic anemia, folate deficiency anemia, neutropenia, thrombocytopenia, and pancytopenia. While adverse effects on erythrocytes are rare, the rates of leukopenia, neutropenia, and thrombocytopenia are highly variable. In a hospital drug monitoring program, leukopenia or neutropenia occurred in 0.4% of 1809 patients treated with co-trimox-azole (54), and thrombocytopenia of mild-to-moderate degree in 0.1% (54,55), similar to figures recorded in other studies (56,57). Pancytopenia is an extremely rare form of adverse reaction to sulfonamides (58). 

Acute thrombocytopenia is rarely associated with the newer sulfonamides (4,93,94). The structurally related sulfonylureas and thiazide diuretics can also cause allergic thrombocytopenia (95). Although some in vitro tests have been reported to predict the occurrence of thrombocytopenia, none of these has been used routinely (96,97). Furthermore, a negative test result with a drug does not definitely exclude it as the responsible allergen. 

Severe adverse drug reactions with trimethoprim and co-trimoxazole are rare (12-14). This also applies to children (15). The adverse effects of co-trimoxazole correspond to those expected from a sulfonamide (16). In HIV-infected patients, adverse effects of co-trimox-azole are more frequent and more severe (17-19). Hematological disturbances due to co-trimoxazole include mild anemia, leukopenia, and thrombocytopenia, which may be due to folic acid antagonism. Serious metabolic disturbances that are associated with trimethoprim include hyperkalemia and metabolic acidosis. Trimethoprim can cause hypersensitivity reactions. However, with co-trimoxazole, the sulfonamide is generally believed to be more allergenic (12). Generalized skin reactions predominate. Other effects, such as anaphylactic shock, are extremely rare (20-22). Carcinogenicity due to trimethoprim or co-trimoxazole has not been reported. 

Most hematological adverse effects associated with trimethoprim have been reported with co-trimoxazole. These include macrocytic and megaloblastic anemia, aplastic anemia, neutropenia, hypersegmentation of leukocytes, thrombocytopenia, and pancytopenia (12,61-63,75-79). Sulfonamides alone have not been associated with folate deficiency, but in combination with trimethoprim they can deplete folate stores in patients with preexisting deficiency of folate or vitamin B12 (80). Treatment with co-trimoxazole can impair the function of mobilized autologous peripheral blood stem cells (81). 

Adverse effects that are not dose related most commonly include rash, fever, or hepatotoxicity, as well as relatively uncommon but serious reactions such as bone marrow suppression, thrombocytopenia, pancreatitis, and hepatitis. For most patients with idiosyncratic reactions, sulfasalazine must be discontinued. In some patients who have experienced allergic reactions to sulfasalazine, a desensitization procedure can be instituted. By gradually increasing sulfasalazine dosage over weeks to months, patient tolerance has been improved. Most of the idiosyncratic reactions observed with sulfasalazine are similar to those with the class of sulfonamides in general. 

Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones do not exacerbate symptoms of folic acid deficiency. The answer is (D). 

Agranulocytosis occurs in 0.1 % of cases after sulfadiazine and also occurs after other sulfonamides. The myelotoxic effect is demonstrated as impaired development of the myeloblasts. Granulocytopenia is not related to the applied dosage and as a rule appears after 10 days treatment. Slight passing thrombocytopenia is frequent, but serious thrombocytopenia and aplastic anemia are rare. Isolated peripheral eosinophilia can be observed, disappearing rapidly after cessation of sulfonamides. It can also appear in combination with other signs of hypersensitivity (Thirkettle et al. 1963 Johnson and Korst 1961). 

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]. 

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