benzofurans and Drug-Hypersensitivity

Topics: Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Lung Diseases; Pulmonary Fibrosis; Time Factors

Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compounds for clinical use was precluded by the observation that they cause dermal sensitization in guinea pigs. A correlation between electrophilicity, as assessed by in vitro reactivity with reduced glutathione, and dermal sensitization potential was further documented.

Topics: Administration, Topical; Animals; Benzofurans; Carbonic Anhydrase Inhibitors; Chemical Phenomena; Chemistry; Chemistry, Physical; Drug Hypersensitivity; Glutathione; Guinea Pigs; In Vitro Techniques; Indoles; Kinetics; Ocular Hypertension; Oxidation-Reduction; Rabbits; Structure-Activity Relationship; Sulfonamides

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Child; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Photosensitivity Disorders

Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy.

Topics: Acute Kidney Injury; Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Humans; Kidney Diseases; Lymphocytes; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Fibrosis; Therapeutic Irrigation

Topics: Alveolitis, Extrinsic Allergic; Amiodarone; Benzofurans; Drug Hypersensitivity; Humans

A 69 year-old woman with no previous history of lung disease was treated with 500 mg of Amiodarone per week. After 21 months of treatment, she developed a clinical picture of alveolitis with fibrosis, which was confirmed by histological examination. No other drug known for its fibrotic properties had been administered. Treatment with Nifedipine and Isosorbide dinitrate had been prescribed prior to the Amiodarone. Simply stopping the Amiodarone led to a regression or disappearance of the clinical, radiological and functional signs. Immunological investigations revealed the presence of antinuclear antibodies and a positive lymphoblastic transformation test for the drug, which are the abnormalities that one finds in other types of drug-induced fibrosis (nitrofuradantin). A new finding was the presence of cutaneous immunofluorescence of granular deposits of IgG, IgM and complement at the dermo-epidermal junction. So far, there have been 13 cases of lung disease related to the administration of Amiodarone reported in the literature.

Topics: Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Pneumonia; Pulmonary Fibrosis

Topics: Alveolitis, Extrinsic Allergic; Amiodarone; Benzofurans; Drug Hypersensitivity; Humans

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

Topics: Aged; Alveolitis, Extrinsic Allergic; Amiodarone; Benzofurans; Cell Migration Inhibition; Drug Hypersensitivity; Humans; Leukocyte Count; Leukocytes; Male; Pulmonary Fibrosis; Skin Tests; T-Lymphocytes; Time Factors

Topics: Amiodarone; Benzofurans; Drug Hypersensitivity; Dystonia Musculorum Deformans; Female; Humans; Metoclopramide; Uremia

Topics: Antihypertensive Agents; Benzofurans; Cornea; Diuretics; Drug Hypersensitivity; Electrocardiography; Eye Diseases; Heart; Heart Diseases; Humans; Iatrogenic Disease; Lupus Erythematosus, Systemic; Quinidine

Topics: Benzofurans; Dermatitis, Contact; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed