Pharmacology of the Endocrine System Thyroid gland

Topics Pituitary and hypothalamic hormones Thyroid and antithyroid Drugs Adrenal Drugs Pancreatic Drugs Gonadal hormones and inhibitors

Thyroid and Anti-Thyroid Drugs

Physiology of the Thyroid Gland Secretes thyroid hormones, such as thyroxine and calcitonin, which regulate metabolism and growth. Composed of epithelial cells specialize in the absorption of iodine and secretion of thyroid hormones.

Synthesis of Thyroid Hormones

Mechanism of Thyroid Hormone Activation in Body . Thyroxin crosses the cell membrane passively or by active diffusion In the cell Deiodinase cleaves the iodine at position 5 to yield triiodithronine (T3) and enters the nucleus and attached to specific receptors

thyrotropin-releasing hormone (TRH) thyroid-stimulating hormone (TSH)

Hormones T3/T4 h TSH Hormone Function h metabolic rate Stimulated by T3/T4 h metabolic rate h protein synthesis h energy production Most important hormone in day today regulation of metabolic rate i metabolic rate h TSH

Effects on Metabolism Thyroxin increases the body’s basal metabolic rate, BMR, to maintain. electrochemical gradient in cell Stimulates carbohydrate metabolism and lipolysis, or the break down of fats. Affects protein synthesis. Increases the body’s sensitivity to cathecholamines, i.e. adrenaline

Hypothyroidism Insufficient amount of thyroid hormone synthesized causing lethargy and weight gain, with many other symptoms.

Treatment for hypothyroidism Hormone replacement therapy Levothyroxine—Synthetic T4 Liothyronine—Synthetic T3 Liotrix—Combination of synthetic T4 and T3

Treatment for hypothyroidism (con,t) Because thyroid hormones serve to increase heart rate, T4, the inactive form, is typically administered to older patients who have an increased risk for heart attack on account of their age. Synthetic T3 is reserved for younger patients, who do not have a history of heart problems and for individuals non-responsive to T4 treatment.

A 9-year-old girl with severe hypothyroidism A 9-year-old girl with severe hypothyroidism. B The same girl 1 year after treatment with thyroid hormone replacement. Note the return to normal facial appearance.

Adverse reactions Hyperthyroidism-like features Cardiovascular toxicity (arrhythmias, angina, and infarction) CNS stimulation, insomnia.

Hyperthyroidism Over production of thyroid hormones. Symptoms include fatigue, weight lose, rapid heart beat, anxiety, swollen eyes, and sensitivity to hot temperatures.

Drugs used in hyperthyroidism Thiouracil Propylthiouracil Methimazole Carbamizole─degraded to methimazole in the body Radioactive Iodine

Thiouracil Inhibits thyroid hormone synthesis by irreversibly binding to thyroid peroxidase inhibiting the attach of iodine to the tyrosine residue of thyroglobulin. Effective in the long-term treatment of hyperthyroidism. 6-8 weeks before maximum effect of the drug achieved. Since thyroxin storage needs two weeks to be depleted in the thyroid gland

Side Effects Include headache, nausea, vomiting, itchy skin and rash, and muscle aches and pains. Serious liver damage, agranulocytosis and vaculitis Administering too high a dosage of anti-thyroid drugs can cause hypothyroidism. All cross the placenta so they are teratogenic, but PTU is safer because its high protein binding.

Radioactive iodine (131I) Rapidly taken, then is incorporated into thyroglobulin. Leads to partial or total destruction of the gland by emission of beta particles. Damage to surrounding tissue is minimal.

Side effects and toxicity Thyroid storm for long term hypothyroidism

Iodine . Higher dose of iodine is used to reduce gland size, vascularity and fragility, prior to surgery Small dose of iodine used for prophylaxis Adverse: hypersensibility reaction, brassy taste, burning of mouth and gums.

THYROID GLAND DISORDERS Treatment: Reducing thyroid hormone synthesis: Antithyroid drugs (Methimazole, Propylthyouracil) Radioiodine (131I) Subtotal thyroidectomy Reducing Thyroid hormone effects: Propranolol Glucocorticoids Benzodiazepines Reducing peripheral conversion of T4 to T3 Propylthyouracil Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

THYROID GLAND DISORDERS Treatment: Special considerations: Thyrotoxic crisis or Thyroid storm: It´s a life-threatening exacervation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. Mortality rate reachs 30% even with treatment It´s usually precipitated by acute illness, such as: Stroke, infection,trauma, diabeic ketoacidosis, surgery, radioiodine treatment Propylthyouracil IV or Nasogastric tube Radioiodine (131I) Propranolol Glucocorticoids Benzodiazepines Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

THYROID GLAND Thyroid also secretes calcitonin which regulates plasma calcium required for muscle and nerve function.

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