Anti thyroid drugs

Anti thyroid drugs

1. Thyroid inhibitors

2. Thyrotoxicosis Excessive secretion of thyroid hormones Main causes: - Graves’ disease – autoimmune, IgG antibodies to TSH receptor - Toxic nodular goiter – produce thyroid hormone independent of TSH

3. Classification Anti thyroid drugs : - propylthiouracil , methimaole , carbimazole Ionic inhibitors : - thiocyanates , perchlorates, nitrates Inhibit hormone release :- iodine, iodides of Na, K Destroy thyroid tissue :- radioactive iodine Other goiterogens : lithium, amiodarone , sulfonamides, paraaminosalicylic acid, phenobarbitone , phenytoine , carbamazepine, rifampin

4. Antithyroid drugs ( thioamides ) Mech of action : Bind to the thyroid peroxidase and prevent oxidation of iodide/ iodotyrosil residues Inhibits iodination of tyrosine residues in thyroglobulin Inhibit coupling of iodotyrosine residues to form T3 and T4 Goiter is due to raised TSH levels as a consequence of negatie feedback mechanism Propylthiouracil also inhibits peripheral conversion of T4 to T3

5. Pharmacokinetics: Quickly absorbed orally Widely distributed in body Enter milk and cross placenta Metabolized in liver Excreted in urine Carbimazole acts by getting converted to methiamzole in the body

6. Adverse effects: Hypothyroidism and goiter, reversible on stopping the drug GI intolerance, skin rashes and joint pain, loss or graying of hair, loss of taste, fever and liver damage Rare but serious effect is agranulocytosis

7. Use: Carbimazole is more commonly used Propylthiouracil is preferred in thyroid strom Control Grave’s disease and toxic nodular goiter As a definitive therapy : in Grave’s disease – young patients with short history and small goiter - In toxic nodular goiter – in elderly patient less responsive to I 131

8. Preoperatively : young patients with florid hyperthyroidism Along with I 131 : Initial control with antithyroid drugs – 1 – 2 wks gap – radioiodine dosing – resume antithyroid drug after 5-7 days and gradually withdraw over 3 months Preferred in older patients In pregnancy propylthiouracil is preferred

9. Advantages: No surgical risk, scars, injury to parathyroid glands or recurrent laryngeal nerve Hypothyroidism, if induced, is reversible Can be used in children and young adults

10. Disadvantages: Prolonged treatment is needed Not predictable in uncooperative patients Drug toxicity

11. Ionic inhibitors Inhibit iodine trapping Perchlorate is 10 times more potent than thiocyanate They are toxic and not clinically used now Thiocyanates – liver, kidney, bone marrow toxicity Perchlorates – rashes, fever, aplastic anaemia , agranulocytosis

12. Iodine and iodides Fastest acting thyroid inhibitor Gland will shrink, less vascular and firm Colloid will restore Peak effects are seen in 10-15 days, after which thyroid escape occurs and thyrotoxicosis may return All facets of thyroid function seem to be affected, most important is inhibition of hormone release Excess iodine inhibits its own transport and attenuates TSH induced thyroid stimulation

13. Uses: Preoperative preparation : in Graves disease iodine is given for 10 days just preceding surgery to make the gland firm, less vascular and easier to operate Thyroid strom : Lugol’s Iodine 6-10 drops or iodine containing radiocontrast media can be used to stop release of T3 and T4 Prophylaxis of endemic goiter : as iodized salt Antiseptic : as tincture iodine, povidine iodine

14. Adverse effects: A cute: occurs in individuals sensitive to iodine. Swelling of lips, eyelids, angioedema of larynx, fever, joint pain, haemorrhages , thrombocytopenia, lymphadenopathy Chronic: inflammation of mucous membranes, salivation. Rhinorrhoea , sneezing, lacrimation, headache, rashes Symptoms regress on stopping the drug

15. Long term and high dose – hypothyroidism Flaring of acne in adolescents Foetal or infantile hypothyroidism Thyrotoxicosis in multinodular goiter

16. Radioactive iodine Stable isotope is I 127 Radioactive isotope is I 131 with halflife 8 days Emit gamma rays and beta rays I 127 used in tracer studies I 131 used for destruction of thyroid tissue I 131 concentrated in thyroid, incorporates in colloid, emit beta rays Follicular cells are most effected

17. Radioactive iodine is administered as sodium salt of I 131 dissolved in water and taken orally Diagnostic – 25 – 100 µ curie is given Therapeutic: - in hyperthyroidism- 3-6 m curie; response is slow, starts after 2 weeks, peak at 3 months Thyroid status is evaluated after 3 months Metastatic carcinoma of thyroid – I 131 is used as palliative therapy after thyroidectomy

18. Advantages: Simple, op basis, inexpensive No surgical risk, scars or injury to parathyroid gland or recurrent laryngeal nerve Once hyperthyroidism is controlled, cure is permanent

19. Disadvantages: Hypothyroidism Long latent period of response Contraindicated during pregnancy Not suitable for younger patients

20. Beta blockers Propranolol used to rapidly alleviate manifestations of thyrotoxicosis due to sympathetic overactivity like palpitations, tremors, nervousness, severe myopathy They are used in - While awaiting response to propylthiouracil / carbimazole / I 131 - Along with iodide in preoperative preparation - Thyroid strom

21. Treatment for thyroid strom (crisis) Emergency due to decompensated hyperthyroidism Nonselective beta blockers like propranolol 1-2 mg slow i.v followed by 40 – 80 mg oral every 6 hrs Propylthiouracil 200 – 300 mg oral 6 hrly Iopanoic acid 0.5 – 1 g OD oral or ipodate Corticosteroid s – hydrocortisone 100 mg i.v , 8 hrly followed by oral prednisolone Diltiazem – 60 – 120 mg Bd oral to control tachycardia Rehydration, anxiolytics, external cooling and appropriate antibiotics