Anti thyroid medications Anti thyroid medications Nuwan Gunapala Registrar WD 21/40B

Overview Thyroid physiology Treatment options ◦ Thyoamides ◦ Iodide ◦ Steroids ◦ Lithium ◦ Other drugs

Thyroid physiology Thyroid hormones are iodine containing amino acids Dietary Iodide are absorbed and transfer in to thyroid. Some of iodide secret via bile and reabsorb through enterohepatic circulation Iodide enters to thyrocytes via sodium iodide symporter

Iodide enters to colloid through apical membrane via a transporter called pendrin Thyroid peroxidase enzyme located at apical membrane of thyrocytes convert iodide to iodine and attach it to globulin - iodotyrosines Iodotyrosines condensed to form tri and tetra iodotyrosines – thyroid peroxidase When there is a need these T4 and T3 molecules released in to blood.

Thyoamides Mechanism of action ◦ Inhibit thyroid peroxidase and prevents organification of iodine and condensation of iodotyrosines Propylthiouracyl also inhibit peripheral conversion of T3

Thioamides Carbimazole Methimazole Propylthiouracil Methylthiouracil

Characteristics of thioamides Results appear later – 3 to 4 wks symptoms relieved and 3 to 4 mts BMR normalize Long term results in thyroid hyperplasia Methimazole is potent 10 times as propylthiouracil Propylthiouracil is preferable in pregnancy: ◦ It crosses the placenta less readily ◦ Is not secreted in breast milk

Propylthiouracil has an early onset of action, so use in thyroid storm

Adverse reactions 1. Long-term use leads to thyroid hyperplasia; 2. Pruritic maculopapular rash is the most common adverse reaction 3. The severe adverse reaction is agranulocytosis

Iodide In pharmacologic doses the major action is to inhibit hormone release(Wolff–Chaikoff effect) Improvement in thyrotoxic symptoms occurs within 2 -7 days, after that escape mechanism Decrease of size & vascularity of the hyperplastic gland Decrease of size & vascularity of the hyperplastic gland Iodides in pregnancy should be avoided, since they cross the placenta and can cause fetal goiter

Clinical use Treatment of hyperthyroidism 1. Operation preparation 2. Thyroid crisis. Adverse reactions 1. Rash 2. Swollen salivary glands, mucous membrane ulcerations

Lithium Reduce secretion of thyroglobulin in to colloid Also reduce release of hormones from throglobulin in to circulation Indications ◦ elevation of transaminases ◦ agranulocytosis ◦ allergic reaction ◦ resistance to propylthiouracil therapy

Steroides Corticosteroids reduce T 4 to T 3 conversion and possibly affect the autoimmune process in Graves’ disease Use in Graves disease and thyroid storm Also use in graves eye disease

Other drugs Amioderone Barbiturates accelerate T 4 breakdown (by enzyme induction) and are also sedative Because thyrotoxic patients have an increased thyroid hormone enterohepatic circulation, cholesteramine has a role in treatment

Symptoms controlling drugs Propranolol will control tachycardia, hypertension, and atrial fibrillation Diltiazem, can control tachycardia in patients in whom beta-blockers are contraindicated