Thyroid hormones & antithyroid drugs.ppt

the presentation is helpful to pharmacy students semester V, also to medical students.
Including thyroid hormones role, classification of antithyroid drugs/agents useful in treatment of various thyroid gland disorders

1. THYROID HORMONES AND ANTI-THYROID DRUGS
Prepared by
Ms Swati A Tekale
Assistant Professor
Department of Pharmacology
Nanded Pharmacy College, Nanded

2. THYROID GLAND
The function is to synthesize, store
and secrete the hormone Thyroxine (T4)
Triiodothyronine(T3) and Calcitonin.
The secretions are under control of Thyrotropic hormone(TSH) from
anterior pituitary.
The hormones are essential for normal energy metabolism, body growth &
mental developement

3. Biosynthesis, Release and Transport:
Steps;
1.Uptake of iodide i e iodide trapping.
2.Oxidation of iodide to free iodine and iodination of tyrosine.
3.Formation of thyroxine and triiodothyronine by coupling of iodotyrosines.
4.Proteolysis of thyroglobulin and release of thyroxine & triiodothyronine into blood.

4. Metabolism and excretion:
•Only free forms of hormones i e T4 0.05% and T3 0.5% are active with their
half lives as 7 & 2 days .
•Metabolised by Liver and Kidney.
•Products of catabolism include tetraiodothyroacetic acid (TETRAC) and
Triiodothyroacetic acid (TRIAC).
•TETRAC & TRIAC are conjugated with glucuronides and get deiodinated.
•The conjugates are excreted via bile in stools.

5. TRH
Anterior pituitary
TRH
Thyroid
Tissues
T3 & T4
Tissues
Fig: Control of thyroid hormone Production
Hypothalamus

6. Actions :
Increased calorigenesis and raised BMR
Increased Carbohydate and Protein metabolism.
Increase Cholesterol turnover.
Increased Heart rate, contractility and Cardiac output.
Increase calcium mobilization from bone.
Regulation of water and electrolyte balance.
Normal development of nervous system.

7. Mode of Action:
•High affinity binding sites i e receptor for
T3 & T4 are present in nucleus, Mitochondria and
Plasma membranes of cells.
•The affinity of these receptors for T4 is about 10 times lower than that of T3.
•The hormones firstly by binding to receptors on cell surfaces increase uptake of
glucose & amino acids,
•Also enters the cell to interact with receptors on mitochondria & Chromatin material
which results in increased synthesis of RNA leading to accelerated protein synthesis
& enhanced enzymatic and cellular activity.
•The thyroid hormones are essential for optimal growth, development & functioning
of all body tissues & are most important in development of CNS.

8. Therapeutic uses:
1.Thyroid deficiency states Hypothyroidism secondary to anterior pituitary
disfunction.
2.Chronic thyroiditis,non-toxic and nodular goitre.
3.Hyperlipidemia associated with hypothyroidism.
4.Thyroid hormones are mainly used in myxodema(swelling of skin) in
adults & cretinism (iodine deficiency,less physical & mental growth) in
childrens , where they serve as replacement therapy.
5. Thyroid hormones may be given as trial in various disorders like obesity,
hypogondia, menopausal abnormalities, infertility, menstrual disorders.

9. Toxicity:
Includes manifestations of hyperthyroidism like
Hyperirritability
Insomnia
Nervousness
Tachycardia
Arrhythmias etc.

10. Parathormone( PTH)
It is a large polypeptide containing 84 amino acids, & is obtained from bovine
parathyroid extract.
The chief physiologic role of PTH is maintenance of calcium, homeostasis
which is an essential requirement for normal body function.
Removal of parathyroid gland results in progressive hypocalcemia, convulsions
& death.
Release of PTH is regulated by calcium ion concentration in blood.
The release is stimulated by fall & inhibited by rise in ionized calcium levels in
plasma.

11. Actions:
PTH primarily raises plasma calcium ion concentration & lowers the plasma
phosphate level & its major effects are exerted on calcium transport in ;
Bone,
Kidney &
Intestine
Bone: PTH leads to resorption of bone, releasing calcium into blood.
PTH stimulate adenyl cyclase activity in bone thereby promotes osteoclastic activity
(Breaking of bone & responsible for bone resorption) and transiently depress
osteoblastic activity
Kidney: PTH inhibits renal tubular reabsorption of phosphate, due to activation of
renal adenyl cyclase which results in increased phosphate clearance & a Phasphaturia
( UTI condition where there is too much phosphorus in urine)
 Intestine : PTH has no direct effect on intestinal calcium transport.

12. Mode of Action:
Precise mechanism is not completely understood.
PTH Astimulates adenyl cyclase activity in bone & kidney cells which leads to
increase in cyclic-AMP formation which is an important factor in regulation of
intracellular calcium ion concentration.
Therapeutic uses:
Only used for control of tetany (Muscular spasm) due to hypothyroidism and
once the tetany has been controlled the treatment is mainly dietic & Vit D .
PTH is used for diagnosis of Psudohypoparathyroidism ( Condition of
resistance to parathyroid hormone having low serum calcium & High phosphate)

13. Toxicity:
Overdose with PTH causes hypercalcaemia which is manifested as weakness,
vomiting, diarrhoea & lack of muscle tone.
Hypersensitivity reaction may occur.
Prolonged use of PTH may lead to Demineralisation of bone

14. Calcitonin (Thyrocalcitonin)
It is a small polypeptide with 32 amino acid & synthesized & secreted by
parafollicular cells of thyroid gland.
Its main action is to produce hypocalcemia by inhibiting bone resorption and
by promoting urinary excretion of cacium & Phosphate.
Calcitonin release is regulated by ionized caicium concentration of blood that
perfusing the thyroid gland.
The Glucagon & Magnesium also stimulate release of calcitonin.

15. Mode of action:
Calcitonin produces hypocalcemia by decreasing osteoclastic activity &
increasing osteoblastic activity in bone.
Hence it inhibits bone resorption & antagonises the action of PTH.
Exact mechanism of action is unknown but the adenyl cyclase system does
not appear to be directly involved in its action on kidneys.
Therapeutic uses:
Calcitonin use in hypercalcaemic state is limited due to its short duration of
action & rapid development of resistance.
Salmon calcitonin has longer half life & used in osteoporosis, pagets
disease( replacement of old bone tissues by new bone tissues)

16. Toxicity:
Inflammatory reactions may be caused at site of injection.
May produce mild hypocalcaemia but does not produce tetany

17. Vitamin D
 It designates a group of related sterols active against rickets ( Children bone
disorder Where bone soften and become prone to fracture)
The effects of Vit D i e Cholecalciferol are mainly due to its more potent
hydroxylated Metabolites formed in liver & kidneys.
Dihydrotachysterol is used to correct hypocalcaemia of hypoparathyroidism &
to treat acute, chronic & latent forms of parathyroid therapy.

18. Mode of Action:
Vitamin D & its active metabolites precipitate in regulation of plasma calcium ion
concentration by acting on bone, kidney and intestines,
In bone, the Vit D maintains stores of calcium in mitochondria & hence essential
for PTH induced bone resorption.
In kidneys its metabolite increase calcium reabsorption from proximal tubules.
In intestines its metabolites promote calcium absorption.
Toxicity:
 Hypervitaminosis-D occurs if individual with normal Vit D sensitivity
receives dose of 150,000 units or more daily for prolonged period.
It is characterized by Decalcification of bones, hypercalcaemia,
hyperphosphataemia & metastatic calcification.

19. Antithyroid Drugs
In Hyperthyroidism there is an excessive secretion & hyperactivity of thyroid
hormones which occurs in two forms;
1-Diffuse toxin goitre (graves disease) in which there is thyrotoxicosis &
opthalmopathy.
2- Toxic nodular goitre ;it generally occurs in older patient of non-toxic goitre.
These manifestations are mainly due to increase in BMR, neuromuscular activity &
activity of sympathetic nervous system.
Includes symptoms of fatigue, irritability, agitation, loss of weight, excessive
sweating, hypertension.
To manage this thyrotoxicosis the Anti-thyroid drugs, radioactiveiodine are given or
there is removal of part of thyroid gland.

20. Classification:
Based on Mode of action;
1.Inhibitors of thyroxine synthesis
Ex. Propylthiouracil, Methylthiouracil,Methimazole, Carbimazole
2. Drugs that destry thyroid tissue
Ex. Radioactive iodine (I131)
3. Antiadrenergic drugs
Ex. Prapranolol, Ganethidine.
4. Drugs with uncertain mide of action
Ex. Potassium iodide, Sodium iodide, lugols iodine
5. Inhibitors of iodide trapping
Ex. Thiocynates, perchlorates.

21. Inhibitors of thyroxine synthesis
Thiamides:
Propylthiouracil: It is a thioamide which is prototype in the group & has
completely replaced the parent compound thiouracil.
It inhibits the synthesis of thyroid hormones in usual doses, but can not
interfere with already formed & stored thyroxine in the gland.
Hence its effect doesnt appear until already available hormone supply is
exhausted & such time lag in antithyroid effect may range from several days
to weeks.
By using these antithyroid drugs, when thyroxine synthesis is stopped then
secretion of TSH is increased which leads to thyroid hyperplasia &
increases vascularity which manifested as enlargement of gland.

22. Because of this they are also labelled as goitrogens.
Methylthiouracil is having equal potency as that of propylthiouracil but is
less desirable due to its allergic manifestations.
The methimazole is also chemically related to propylthiouracil having
similar actions and uses but it is about 10 times more potent than
propylthiouracil

23. Mode Of Action:
The antithyroid drugs inhibit the formation of thyroxine by interfering with;
i) Iodination of tyrosine & ii) Coupling & Condensation of Iodotyrosines.
They can also block oxidation of iodides.
They inhibit cytochrome oxidase & peroxidase enzyme systems.
Therapeutic uses:
Hyperthyroidism (graves disease), in such condition relief is marked by fall
in BMR, increase in body weight & reversion of arrhythmias.
Preparation of thyrotoxic patient for surgical treatment.
Contraindications:
As thioamides cross the placenta, they can cause foetal goitre, hence use
should be minimized during pregnancy.
Toxicity:
Goitrogenic action, Allergic reaction may occur,Hypothyroid state may occur

24. References
K. D. Tripathi,(2003.) “Essentials of Medical Pharmacology,” 5th Edition,
Jaypee Brothers Medical Publishers (P) Ltd

Barar, F. S. K. (2000). Essentials of Pharmacotherapeutics (4th ed.). S. Chand &
Company Ltd.