methimazole and Asthma

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.

Topics: Abnormalities, Drug-Induced; Acetaminophen; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Analgesics, Non-Narcotic; Anti-Asthmatic Agents; Antidepressive Agents; Antiemetics; Antithyroid Agents; Asthma; Congenital Abnormalities; Depressive Disorder; Female; Humans; Hyperthyroidism; Leukotriene Antagonists; Maternal-Fetal Exchange; Methimazole; Morning Sickness; Ondansetron; Pregnancy; Pregnancy Complications; Propylthiouracil; Teratogens

β(2)-agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β(2)-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hydrogen peroxide (H(2)O(2)) and nitrite (NO(2)(-)), both absorption spectroscopy and mass spectrometry indicated formation of a new metabolite with features expected for the nitrated drug. The new metabolites showed an absorption maximum at 410 nm and pK(a) of 6.6 of the phenolic hydroxyl group. In addition to nitrosalbutamol (m/z 285.14), a salbutamol-derived nitrophenol, formed by elimination of the formaldehyde group, was detected (m/z 255.13) by mass spectrometry. It is noteworthy that the latter metabolite was detected in exhaled breath condensates of asthma patients receiving salbutamol but not in unexposed control subjects, indicating the potential for β(2)-agonist nitration to occur in the inflamed airway in vivo. Salbutamol nitration was inhibited in vitro by ascorbate, thiocyanate, and the pharmacological agents methimazole and dapsone. The efficacy of inhibition depended on the nitrating system, with the lactoperoxidase/H(2)O(2)/NO(2)(-) being the most affected. Functionally, nitrated salbutamol showed decreased affinity for β(2)-adrenergic receptors and impaired cAMP synthesis in airway smooth muscle cells compared with the native drug. These results suggest that under inflammatory conditions associated with asthma, phenolic β(2)-agonists may be subject to peroxidase-catalyzed nitration that could potentially diminish their therapeutic efficacy.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Ascorbic Acid; Asthma; Breath Tests; Bronchi; Catalysis; Child; Cyclic AMP; Dapsone; Humans; Hydrogen Peroxide; Mass Spectrometry; Methimazole; Nitrites; Peroxidases; Receptors, Adrenergic, beta-2; Thiocyanates

Topics: Airway Obstruction; Asthma; Diagnosis, Differential; Goiter, Nodular; Humans; Methimazole

We report the case of a 67-year-old woman who suffered from a severe asthma exacerbation as a consequence of an antithyroid drug treatment prescribed for her multinodular, hyperfunctioning goiter. Asthma symptoms were associated with a very significant increase in the number of eosinophils, detected in both blood and induced sputum.

Topics: Aged; Antithyroid Agents; Asthma; Female; Humans; Methimazole

To investigate the possible participation of immunoglobulin E (IgE) in the autoimmune process of Graves' disease, incidence of elevation of serum IgE level, TSH receptor antibody (TRAb), and thyroid status were studied in 66 patients with hyperthyroid Graves' disease, 54 patients with Hashimoto's thyroiditis, 19 patients with bronchial asthma, and 15 patients with pollen allergy. In hyperthyroid Graves' patients, elevation of serum IgE levels (> or = 170 U/mL) was found in 19 of 66 patients (29%), 11 of whom had hereditary and/or allergic conditions. Elevations of serum IgE levels were found in 63% of patients with bronchial asthma and in 40% of patients with pollen allergy. Mean values of serum IgE were the same in patients with hyperthyroid Graves' disease and with bronchial asthma. During methimazole treatment TRAb decreased without fluctuation of IgE levels in both groups. The decrease in TRAb was significantly greater in patients with normal IgE than in patients with IgE elevation. After prednisone administration, reduction in TRAb was greater in patients with normal IgE than that in patients with IgE elevation. High incidence of IgE elevation in hyperthyroid Graves' disease and slower reduction in TRAb in association with IgE elevation suggest a difference in the autoimmune processes in Graves' disease with and without elevation of IgE.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Asthma; Female; Glucocorticoids; Graves Disease; Humans; Hypersensitivity; Immunoglobulin E; Male; Methimazole; Middle Aged; Pollen; Prednisone; Thyroid Diseases; Thyroid Gland