Extrathyroidal actions of antithyroid thionamides.
Some compounds having thionamide structure inhibit thyroid functions. Such antithyroid thionamides include mercaptomethylimidazole (methimazole), thiourea and propylthiouracil, of which mercaptomethylimidazole is widely used to treat hyperthyroidism. Undesirable side effects develop from these drugs due to extrathyroidal actions. Antithyroid thionamides inhibit lactoperoxidase which contributes to the antibacterial activities of a number of mammalian exocrine gland secretions that protect a variety of mucosal surfaces. These drugs stimulate both gastric acid and pepsinogen secretions, thereby augmenting the severity of gastric ulcers and preventing wound healing. Increased gastric acid secretion is partially due to the H2 receptor activation, and also through the stimulation of the parietal cell by intracellular generation of H2O2 following inactivation of the gastric peroxidase-catalase system. Severe abnormalities may develop in blood cells and the immune system after thionamide therapy. It causes agranulocytosis, aplastic anemia, and purpura along with immune suppression. Olfactory and auditory systems are also affected by these drugs. Thionamide affects the sense of smell and taste and also causes loss of hearing. It binds to the Bowman's glands in the olfactory mucosa and causes extensive lesion in the olfactory mucosa. Thionamides also affect gene expression and modulate the functions of some cell types. A brief account of the chemistry and metabolism of antithyroid thionamides, along with their biological actions are presented.
Bandyopadhyay
Uday
U
Department of Physiology, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Calcutta 700 032, India.
Biswas
Kausik
K
Banerjee
Ranajit K
RK
D000818:Animals; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D006309:Hearing / Q000187:drug effects; D007165:Immunosuppression Therapy; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors; D008713:Methimazole / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009831:Olfactory Mucosa / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors; D051381:Rats; D013854:Thioamides / Q000009:adverse effects*
D013956:Antithyroid Agents; D004791:Enzyme Inhibitors; D013854:Thioamides; D008713:Methimazole; D007784:Lactoperoxidase; D009195:Peroxidase