Thyroid and antithyroid drugs

OBJECTIVES 1 . Know the locations and the function of the gland Know the causes, symptoms and terminologies associated with hypo and hyper thyroidism Know the modes of treatment of hypo and hyper thyroidism Know the side effects of these treatments Describe the synthetic pathways for thyroid hormones, role of Iodine Know the relative concentrations, durations of action and potencies of T3and 2. 3. 4. 5. 6 . 7. T. , Describe the mechanism of action of T3and T and their functions. , 3 94 THYROID AND O I. Introduction History, Location, Function O I D DRUGS 11. Hypothyroidism A. Causes 1 . 2. 3. 4. 5. Surgical thyroidectomy 6. 7. Radio-iodine therapy Congenital absence of the gland Insufficient iodide intake Inadequate TSH Drug induced, Thiobarbs, Sulfonamides, Aniline, Nitrate, etc Auto-immune (Hashimoto's disease) .- B. Symptoms: Myxedema (Thickening of skin and subcutaneous tissue) Cretinism (at birth): P w face, large tongue, thick lips, short extremities, late and abnormal dentition (these are due to depressed physical growth and failure of the mandibles to fuse), mental retardation Gulls disease in adults Goiter (non-toxic): Hypertrophy of thyroid gland Organs affected: skin, eyes, bone, muscle, GI, CV, CNS Hypometabolism, decrease activity (e.g. C.O., Bone turnover, appetite, energy, mental function, sexual acitivity), abnormal skin temp. and constipation C. ID. Treatment: Replacement Therapy (See Thyroid Drugs CharL) Hyperthyroidism A. Types 1. 2. Graves disease or Thyrotoxic goiter (disorder of immune system) (Diffuse thyroid enlargement and possible exopthalmus) Plummer's disease (Hypersecretion &om 1or more nodules. No expothahus) 395 B. Symptoms Hypermetabolism and increased activity (e.g. C.V. demand, tachycardia, arrhythmia) restlessness, sweating, tremor, diarrhea, weight loss despite increase in appetite. C. Treatment 1. 2. S r i a Thyroidectomy ugcl Antithyroid drugs rv. Thyroid Hormones A. B. C. Synthesis and circulation - see Fig. Relative concentration T3 c T , Activity (onset T3> T,; duration T > T3, tM) see Table on Thyroid , drugs Control mechanism Receptors in cell nuclei Actions: increase 0 2 consumption of cells, PI synthesis D. E. NON-CALORIGNIC I I CALORIGINIC I I I I HCOOH / I NH, I 1 m I I V. Thyroid Drugs A. 396 SUMMARY OF TREATMENT OF HyPO"R0IDISM MainteJlk3JlW Thyroid Extract -(I)* Thyroglobulin -(l)* Levothyrodne -( 1)* 100 mg Onset Several days Several days Several days Peak 10-21 days 10-21 days 10-21 days Duration 3-4 weeks 21-28 days 3-4 weeks 21-28 days 100 mg 0.3 mg 3-4 weeks 21-28 days (.) D-thyroxine - 0 1 * Liothyronine -(3-5)* 3:5:3' 2 ' s -(5)* *Potency 0.1 mg Few hrs. Rapid 3-4 days 10 days B. Route of administration, oral. Purified hormones are injectable. Side effects. Hyperthyroidism. Caution with cardiac patients. C. VI. Antithyroid Drugs A. Drugs inhibiting the synthesis of thyroid hormones 1 . e.g. Sulfonamides, Polyhydricphenols(resorcinol)and Thioamides (contain thiourea nucleus*) e.g. Thiourea, Propylthiouracil, Methimazole, etc. 2. Side effecrs: increase vascularity, leukopenia, agranulocytosis, drug fevsr and skin reactions, a r t h r i t i s and edema of extremities B. Drugs inhibiting Iodide uptake 3 97 1 . Monovalent hydrated anions e.g. Thiocyanate (SCN-) Nitrate (NO,-) Perchlorate (CIO,-), most active Side effects: Aplastic anemia 2. C. Iodide 1. Large dose decrease thyroid function thyroid size and vascularity I.V. solution given before surgery and also in thyroid storm Side effect (common cold symptoms, exfoliate dermatitis, delay response to thioamide. Iodism (Chronic intoxication with iodine) => unpleasant brassy taste, burning sensation in mouth and throat, soreness of the teeth and gums, increased salivation, swelling of eyelids. 2. D. 1311 1 . 2. Destroys thyroid tissue (Gamma and Beta Radiation) small doses unharmful (used diagnostically) Side effects: Hypothyroidism, carcinogenesis Contraindicated in children and in pregnancy E. Propranalol as adjunct therapy to control tremor, palpitation, etc. 3 98