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Published on : Jul 18, 2021 | Views : 3313 | Downloads : 15

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Slide 1-

Thyroid and antithyroid drugs (Abstract) Assoc. Prof. Iv. Lambev E-mail: itlambev@mail.bg www.medpharm-sofia.eu
Slide 2-

Thyroxine (T4) and tri-iodothyronine (T3) THYROID DRUGS
Slide 3-

T3 and T4 are synthesized in the thyroid gland. Inorganic iodine is trapped with great avidity by the gland, oxidized and attached to tyro- sine. Combination of mono- and/or- di-iodinated tyrosine forms T3 and T4. The thyroxine peroxidase is im- portant both in the initial oxidation and the final combination steps.
Slide 4-

Mono-iodotyrosine (MIT) Tyrosine Di-iodtyrosine (DIT) Inorganic iodine Thyroxine peroxidase Thyroxine peroxidase Inorganic iodine
Slide 5-

MIT + DIT DIT + DIT T3 T4 Thyreoglobulin Thyreoglobulin
Slide 6-

Tyrosine Di-iodotyrosine
Slide 7-

T4 = L-Thyroxine
Slide 8-

Synthesis and release of T3 and T4 are controlled by the anterior pitu- itary hormone, thyrotrophin (TSH - thyroid-stimulating hormone). Its secretion is controlled by the hypo- thalamic thyrotrophin-releasing hormone (TRH) and somatostatin. Circulating T3 and T4 exert a nega- tive feedback on the TSH and TRH.
Slide 9-

Adenohypophysis Glandula Thyreoidea TSH Hypothalamus TRH Somatostatin (+) (+) (-) (+) (-) (-) (-) p l a s m a T3 < I > I T4
Slide 10-

Regulation of thyroid hormone synthesis
Slide 11-

Worldwide iodine nutrition
Slide 12-

80 mcg T4 40 mcg T3 200 mcg I 24 hrs:
Slide 13-

Circulating thyroid hormones are highly protein-bound to TBG (thyroxine-binding globulin). Less than 0.1% from T4 is free. Only the free fraction can bind to specific cell receptors.
Slide 14-

Plasma T4: 95% T3: 5% Thyroxine-binding globulin 99.91–99.97%
Slide 15-

AGENTS INLFUENCING PROTEIN- BINDING OF L-THYROXINE (T4) INCREASE estrogens methadone heroin clofibrate tamoxifen DECREASE glucocorticoids aspirin phenytoin carbamazepine furosemide
Slide 16-

T3 is much more biologically active than T4. The plasma half-life of T3 is 36 h. T4 has t1/2 168 h. After entering into cells T4 converts into T3 which binds to receptor protein and inte- racts with DNA in the cell nucleus, causing the synthesis of new messen- ger RNA and hence of new proteins.
Slide 17-

The main effects of T3 and T4: Stimulating of metabolism (which results in a raised basal metabolic rate). Promotion of normal growth and maturation, particularly of the CNS, and skeleton. Sensitization to the effects of catecholamines (DA, NA, Adrenaline).
Slide 18-

Intracellular (nuclear) steroid/thyroid receptors Effector Coupling Time scale Examples gene transcription via DNA hours steroid receptors thyroid receptors vitamin D receptors
Slide 19-

Directly at nuclear receptors: Thyroid hormones (T3, T4) T3 or T4 penetrates the nucleus Combines with their receptors Alters DNA-RNA mediated protein synthesis
Slide 20-

T3&T4 – indications: hypothyroidism T3 is reserved for patients with myxoedemic coma.
Slide 21-

Lack of energy Weight gain Feeling cold Dry skin and hair Constipation Haevy menstrual periods Hypothyroidism Hyperthyroidism Fatigue, weight loss Feeling hot Palpitations, irritability More bowel movements Schorter or lighter menstrual periods
Slide 22-

ppt slide no 22 content not found
Slide 23-

Facial appearance in hypothyroidism
Slide 24-

Jodthyrox (T4 + < I) Levothyroxine (T4) - tabl. 25 mcg Liothyronin (T3) Thyreoidea siccata Thyrotrophin (TSH)
Slide 25-

They are used to treat hyperthyroidism. Thioureas agents Beta-blockers Radioactive iodine (131I) ANTITHYROID DRUGS
Slide 26-

Thiourea agents inhibit thyroxine peroxidase, and therefore the synthesis of T3 and T4. Because of the long half-life of T4, changes in the rate synthesis takes several weeks to lower circu- lating concentrations to normal.
Slide 27-

Propylthiouracil Thiamazole – tabl. 5 mg Carbimazole (prodrug) Thiamazole (Methimazole – USAN)
Slide 28-

Thioureas – adverse effects Agranulocytosis Nausea, taste disturbance Placental transfer and secretion in breast milk can produce neo- natal hypothyroidism (small doses are probably safe).
Slide 29-

Beta-blockers have imme- diate symptomatic effect on palpitation and tremor but do not alter the rate of T3 & T4 synthesis. 131I (t1/2 8 days) is used to treat multinodular toxic goiters. It is taken up by the abnormal tissue.