In this ppt we will get idea about thyroid and anti-thyroid drugs. how and where the thyroid hormone synthesis occur. regulation of thyroid hormone. get brief knowledge about anti-thyroid drugs, their action, MOA, adverse effect of anti-thyroid drugs and uses

1. THYROID AND
ANTITHYROID DRUGS
SUBJECT NAME : ADVANCE PHARMACOLOGY-II
REPRESENTED BY : ANKITA SANDESH HALDANKAR
GUIDED BY : DR. D. S. SHIRODE SIR
M. PHARM 1ST YEAR (PHARMACOLOGY)
D. Y. Patil College Of Pharmacy Akurdi, Pune

2. INTRODUCTION
• Thyroid gland contain follicular cells and parafollicular cells,
secrete thyroid hormone (T3 and T4) whereas the latter
responsible for secretion of calcitonin.
20XX presentation title 2
THYROID CELL THYROID HORMONE FUNCTION
Follicular cells Thyroxine (T4)
Tri-iodothyronine (T3)
Controls metabolism,
regulate body temp. by
calorigenic action.
Control metamorphosis
in amphibians, control
BMR
Parafollicular cells Thyrocalcitonin
(secreted by
parafollicular cells of
thyroid)
Control calcium(Ca++)
level in blood, check
osteoporosis.

3. DISORDER OF THYROID
HORMONE
20XX presentation title 3

4. 20XX presentation title 4
SYNTHESIS, STORAGE AND RELEASE OF T3
AND T4

5. SYNTHESIS, STORAGE AND RELEASE OF T3
AND T4
• STEPS IN THYROID HORMONE SYNTHESIS
1. Iodine trapping / Inhibition of Na+ I symporter
2. Oxidation and iodination
3. Coupling
4. Storage of iodine
5. Released of iodine
6. Peripheral conversion of T4 to T3
1) Iodine trapping :
• drugs acting: Thiocyanate, Fluborite, perchlorate, nitrate
• Iodine is trapped in the follicular cells with Na+:I- is known as iodine trapping.
• This process can be inhibited by thiocyanate, fluoborite, perchlorate and nitrate.
20XX presentation title 5

6. 2. Oxidation and iodination :
• Iodine trapped by follicular cells is carried across the apical membrane by another
transporter termed Pendrin.
• The trapped iodine is transferred across the cell and into the colloid lumen.
• In colloid it is oxidized by membrane bound thyroid peroxidase to form
a. Iodinium ion (I+)
b. Hypoiodous acid (HOI)
c. Enzymes linked hypoiodate ( E-OI)
These oxidized form of iodine combines with tyrosine residue of thyroglobulin to form
a) Monoiodotyrosine (MIT)
b) Di- iodotyrosine ( DIT)
These MIT and DIT are attached to thyroglobulin.
20XX presentation title 6

7. 3. Coupling :
• While still linked to the thyroglobulin MIT and DIT are converted to T3 and T4 with the aid of
the enzyme peroxidase and transaminase.
a) MIT+DIT= T3
b) DIT +DIT= T4
• T4 and T3 while linked to thyroglobulin, are reabsorbed into the cell in form of colloid droplets.
4. Storage of iodine :
• Thyroglobulin containing MIT, DIT, T3 and T4 is transported into the follicular cells by
endocytosis.
• Inside the cells thyroglobulin is broken down by lysosomal proteases.
5. Released of iodine :
• T3and T4 are secreted into the circulation, released MIT & DIT are deiodinated and the release
iodine is reutilized.
6. Peripheral conversion of T4 to T3 :
• Peripheral tissues, especially liver and kidney, convert T4 to T3
• Drugs: Propylthiouracil, Propranolol, Amiodarone and glucocorticoids inhibits peripheral
conversion of T4 to T3
20XX presentation title 7

8. 20XX presentation title 8
REGULATION OF SECRETION
 Secretion of hormone from
the thyroid is controlled by
anterior pituitary by the
elaboration of TSH while TSH
secretion itself regulated by
TRH produced hypothalamus.
• SOMATOSTATIN elaborate by
hypothalamus inhibit not only
GH and PROLACTIN but also
TSH secretion from pituitary.

9. 20XX presentation title 9
RELATION BETWEEN T3 AND T4
T3
(TRIIODOTHYRONINE)
T4 (THYROXINE)
MIT + DIT = T3 DIT + DIT = T4
T3 is less in circulation T4 is the major circulating
hormone
Rapid onset of action Slower onset of action
More potent Less potent
PREPARATIONS

10. 20XX presentation title 10
PHARMACOLOGICAL ACTIONS
1. Growth and development:
 Thyroid hormones required for the normal and development.
 Deficiency leads to – Cretinism (in children), Myxodema (in adult)
2. Metabolism:
 These are catabolic hormone.
 Lipid: T4 and T3 indirectly enhance lipolysis by potentiating the action catecholamine
and other lipolytic hormone.
 Carbohydrates : Carbohydrates metabolism is stimulated causes hyperglycaemia.
 Protein Synthesis of certain protein is increased but overall effect of T3 is catabolic –
increase amount of protein being used as energy source.
3. Calorigenesis:
 T4 and T3 increase basal metabolic rate by stimulation of cellular metabolism.
 Helps in maintaining body temperature.

11. 20XX presentation title 11
4.CVS
T3 and T4 cause hyperdynamic state of circulation which is partly secondary to
increased peripheral demand and partly due to direct cardiac action.
5.Nervous system
Hypothyroidism results in mental retardation.
Hyperthyroidisms result in anxiety, tremor, hyperreflexia and excitability.
6. GIT
Propulsive activity of gut is increased by T3/T4.
Hypothyroid patient is often constipated while diarrhoea is common in
hyperthyroidism.
7. Reproduction
Fertility is impaired in hypothyroidism and women suffer from oligomenorrhoea.
Normal thyroid function is required for maintenance of pregnancy and lactation.
8. Skeletal muscle
Hypothyroidism causes swelling of skin and underlying tissue.
Hyperthyroidism causes increase muscle tone, tremor and weakness

12. 20XX presentation title 12
INTERACTION
• It should be administered in empty stomach to avoid interference by food,
sucralfate, iron,
Calcium and proton pump inhibitors also reduce thyroxine absorption.
 CYP3A4 inducer like Phenytoin and carbamazepine accelerate metabolism of
T4 dose of thyroxine may need enhanced.
USES:
• Cretinism
• Adult hypothyroidism
• Myxoedema
• Nontoxic goiter
• Thyroid nodule
• Papillary carcinoma of thyroid

13. 20XX presentation title 13
1)Cretinism:
Caused due to failure of thyroid development (sporadic cretinism).
Due to extreme iodine deficiency (endemic cretinism).
Mostly during infancy or childhood.
Treatment with thyroxine (8-12 ug/kg) daily physical growth and
development are restored and further mental retardation is prevented.
2)Adult hypothyroidism (Myxoedema):
commonest endocrine disorders - Caused due to autoimmune thyroiditis,
thyroidectomy.
Antibodies generated against thyroid peroxidase or thyroglobuline.-
Causes adult hypothyroidism.
Drugs that can cause hypothyroidism are 13 iodides, lithium and amiodarone
which treated with T4 50ug/day.
Subclinical hypothyroidism- In this disorder free serum thyroxine level increases
but TSH level decreases- This condition treated with T4.

14. 20XX presentation title 14
3) Myxoedema coma:
It is an emergency condition were progressive mental
deterioration caused due to deficient production of thyroid
hormone
(Hypothyroidism).
This condition treated with liothyroinine (T3) but high risk of
cardiac arrhythmia & angina.
I V. dose T3(10µg/8hr).
4) Nontoxic goiter:
Endemic due to iodine deficiency.
Sporadic due to defect in hormone synthesis.
In above cases deficiency of thyroid hormone leads to increases
TSH causes enlargement of thyroid gland treatment with T4.

15. 20XX presentation title 15
5) Thyroid nodule:
When T4 treatment is started TSH synthesis get suppressed causes
normal functioning of nodules function while nonfunctional nodules
not respond.
6) Papillary carcinoma of thyroid:
This is type of cancer caused due to TSH over production; treatment
with T4 causes decreased TSH production.
7) Other uses.
T4 used for treatment of refractory anemia, mental depression,
menstrual disorder or infertility.

16. ANTITHYROID DRUGS
 DEFINITION : “These are the pharmacological agent which are used to lower the
functional capacity of hyperactive Thyroid gland”
• These are the agent used in treatment of Thyrotoxicosis ( excess secretion of thyroid
hormone due to disorder like
1. Grave disease
2. Toxic nodular goiter.
 These are drugs used in the treatment of hyperthyroid condition.
 These drugs acting by reducing thyroid hormone synthesis or release or both.
20XX presentation title 16

17. Classification
20XX presentation title 17

18. 20XX presentation title 18
1)Antithyroid drugs: (Thioamides)
Hormone synthesis inhibitors called Antithyroid drugs.
• Mechanism of action:
Thiocarbamide (S-C-N) group essential for activity.
Antithyroid drugs bind to thyroid peroxidase and prevent oxidation of
iodide/iodotyrosyl residues;
1)Inhibit thyroid peroxidase enzyme.
2) Inhibit coupling of iodotyrosine residues to form T3 and T4 which occurs
as low concentration.
Simply this class drug decreases the output of thyroid hormone from the gland
so decreases the sign and symptoms of thyrotoxicosis.
Propyl Thiouracil- Inhibit conversion of T4-T3- Mostly in type Ist diabetes
mellitus- but methamizole & Carbamazole not have this action.

19. 20XX presentation title 19
Adverse drug reaction:
1)Hypothyroidism and goiter –
2)Other side effects: GI intolerance, Skin rashes, joint pain.
3)loss of hair, loss of taste, fever & liver damage.
4) Agranulocytosis & Jaundice may occurs.
Preparation:
Propylthiouracil(50mg-150mg TDS)
Methimazole (5-10mg)
Carbimaole (5-15mg) (Inhibition T4-T3 peripheral conversion)
USES:
• Thyrotoxicosis: life long
• Pre-operatively to make euthyroid.
ADVANTAGE:
• Less surgical complication

20. 20XX presentation title 20
2) Inhibit thyroid hormone release
• Drugs : Iodine, iodides of Na and K organic iodides
• These drugs are faster acting thyroid inhibitor(Antithyroid).
• High concentration of iodine appear to inhibit almost all steps in the studies of
thyroid hormones and also their release.
• Most important action is inhibition of hormone release – thyroid constipation.
• Iodine mostly orally in solution with potassium Iodide( Lugols iodine)
• Effect seen in 15-15 days. But further treatment causes thyroid escape &
thyrotoxicosis or hyperthyroidism mostly occurs in multinodular goiter.
ADVERSE EFFECT:
• Acute : swelling of lip, eye lid, face, fever, joint pain
• Chronic : ulceration of mucous membrane of mouth, salvation, lacrimation, burning
sensation in the mouth
USES
• Thyrotoxic crisis
• Prophylaxis in endemic goiter

21. 3) Inhibitors of iodide trapping (ionic inhibitors)
• Drugs: Thiocyanate, Perchlorates, Nitrates
• Certain monovalent anion inhibit iodide trapping by NIS
into the thyroid.
• Consequently, T4/T3 cannot be synthesized.
• Thiocyanate also inhibit iodination at high doses.
• They are highly toxic so not used clinically.
20XX presentation title 21

22. 4) Radioactive isotopes
• Ex- 1131, 1123 1125.
• The stable form of isotope of iodine is 1127 but medically useful
isotope is I 131 which having half life 8 days available as sodium
salt; given as oral dose.
• But one of the advantage of radioactive iodine is it produce
necrosis of cell (affected thyroid follicular cell) without damaging
neighboring tissue.
• Radioactive iodine administration as sodium salt of I 131 dissolve
in water & take orally.
Diagnostic:
• 25-100µg given scanning is done at interval (No damage to
thyroid cell occurs with this dose).
20XX presentation title 22

23. 20XX presentation title 23

24. 20XX presentation title 24
Therapeutic:
Indication is hyperthyroidism due to graves disease or toxic nodular goiter.
Advantages:
• Inexpensive.
• No surgical risk, scar or thyroids/recurrent laryngeal nerves after
treatment with I131 Once hyperthyroidism is controlled, cure is
permanently.
Disadvantages:
1) Hypothyroidism: About 5-10% patients of Graves' disease treated with
1311 become hypothyroid.
2) 2) Very slow response was observed for treatment with 1131.
3) 3) during pregnancy drug is Contraindicated because it causes foetal
thyroid destruction.

25. 20XX presentation title 25
5) B- Adrenergic blocker:
• B- blocker –( propranolol, esmolol, atenolol ) antagonise the effect of
thyrotoxicosis.
• Used mostly in thyroid strom
• Thyroid strom ( thyrorotoxic crises) : this is an emergency due to
decompensated hyperthyroidism.
• Very little effect on thyroid function & hyper metabolic state.
B blockers used for tretment of hyperthyroidism in following situation;
1)While response to carbimazole, propylthiouracil or 1131 is low.
2) B blockers given along with iodide for preoperative preparation before
subtotal thyroidectomy.
3) Thyroid storm (thyrotoxic crisis-It is an emergency due to
decompensate hyperthyroidism.) In above condition emergency treatment
with B blockers are given.

26. 20XX presentation title 26
THANK YOU