This document discusses anti-thyroid drugs. It begins by providing an overview of thyroid hormone synthesis and regulation by the hypothalamus, pituitary gland and thyroid stimulating hormone. It then describes the mechanisms of hyperthyroidism and hypothyroidism. The main types of anti-thyroid drugs are described as inhibitors of hormone synthesis, inhibitors of hormone release, and ionic inhibitors. The mechanisms of the major drugs methimazole and propylthiouracil are explained. Adverse effects and therapeutic uses of anti-thyroid drugs are briefly mentioned.

1. {
ZAINUL KHAN
ASSISTANT PROFESSOR
AIPR, LUCKNOW
Anti Thyroid Drugs

2.  Introduction to Thyroid Hormone
 The thyroid gland is among the most significant organs of the endocrine system.
 The hormone secreted by thyroid gland are
 THYROXINE (T4)
 TRIIODOTHYROXINE (T3)
 CALCITONIN
 The follicular cells of thyroid glands have specialized mechanism for the synthesis
of thyroid hormones.
 This follicular cells are regulated by TSH (THYROID STIMULATING
HORMONE ).
 When the level of thyroid decreases in the body it activates HYPOTHALAMUS .
 Hypothalamus secrets TRH (THYROID REGULATING HORMONE ).
 This hormone enters anterior PITUTARY GLAND and the pituitary gland
 secretes TSH .
 This secreted TSH enters thyroid gland and binds to thyroid follicular cells
 and releases T3 and T4.

3. THYROID HORMONE SYNTHESIS
The synthesis of thyroid hormone includes following steps
• IODINE TRAPPING -Active transport of iodine ions into follicular cells is known as
IODINE TRAPPING . In this process sodium is pumped out and iodine is pumped inside the
follicular cells and this iodine is utilised further for the formation of T3 and T4.
• OXIDATION AND IODINATION-Iodide ion Iodine ion
This formed iodine combines with tyrosine residues of thyroglobulin molecule to
form monoiodotyrosine (MIT) and diiodotyrosine (DIT).
• COUPLING - Two molecules of DIT couple to form THYROXINE ( T4 ).
DIT + DIT T4 .
One molecule of MIT and one molecule of DIT couple to form
TRIIODOTHYROXINE ( T3 )
MIT + DIT T3.
Oxidation
Peroxidase
enzyme

4. • HORMONE RELEASE-
The release of thyroid hormone takes place under the control of TSH .
This process involves endocytosis and proteolysis of iodinated
thyroglobulin and results in release of T4 ,T3 , MIT and DIT .
• PERIPHERAL CONVERSION OF T3 and T4
Most of the hormone released from thyroid is T4 which is less potent than T3
therefore T4 is converted into T3 by deiodination reaction in peripheral tissues.

5. Hyperthyroidism
Hyperthyroidism is the overproduction of thyroid hormones by an overactive
thyroid
Thyrotoxicosis is a syndrome of excess of thyroid hormones in the blood, causing
a variety of symptoms that include rapid heart beat, sweating, anxiety, and tremor
Causes of thyrotoxicosis:
1. Most common cause (70%) is Grave`s disease: overproduction of thyroid
hormone by the entire gland (autoimune and IgG to TSH receptors)
2. Toxic nodular or multinodular goiter: lumps in the thyroid gland and
overproduction (independent of TSH)
3. Thyroiditis: Temporary symptoms of hyperthyroidism
4. Tablet intake (thyroid hormone) in excess exogenous.
Hypothyroidism
A decreased activity of the thyroid results in hypothyroidism, failure of
the thyroid gland to produce sufficient thyroid hormone
example - myxoedema.

8. Antithyroid Drugs:
Antithyroid agents prevent or suppress the biosynthesis of thyroid hormones.
Antithyroid agents are used to treat hyperthyroidism by inhibiting the excessive
production of thyroid hormones or by decreasing thyroid hormone activity.
Classification of Antithyroid Drugs
Inhibitor of hormone Synthesis-
Carbimazole
Methimazole
Propylthiouracil
Inhibitor of hormone release-
Iodine
Iodides of Na, k
Organic iodides
Ionic inhibitors-
Thiocynate(-SCN)
Perchlorates(-ClO4)
Nitrates(NO3)
Radioactive iodine-
131 I (Radioactive iodine)

9. Mechanism of action:
1. Inhibitor of hormone synthesis
Methimazole (carbimazole)
Propylthiouracil (PTU)
These 2 are the major drugs used in the treatment of thyrotoxicosis (Carbimazoles
converted to methimazole in vivo).
MOA: These drug inhibit thyroid hormone production by
a) inhibiting thyroid peroxidase which is required in intrathyroidal oxidation of Iodide.
b) by inhibiting the iodination of tyrosine
c) by inhibiting coupling of MIT and DIT to form thyroid hormones
d) Propylthiouracil also inhibits peripheral conversion of T4 to T3 by inhibiting DID -1
enzyme.

10. 2. Inhibitor of hormone release
Iodine
Iodides of Na, k
Organic iodides
MOA: Iodide salts inhibit organification (iodination of tyrosine) and thyroid hormone
release.
These salts also decrease the size & vascularity of the hyperplastic thyroid gland
inhibition of thyroglobulin proteolysis.
The usual forms of this drug are lugol's solution(iodine & potassium iodide) and
saturated solution of potassium iodide.
3. ANION INHIBITORS
Includes monovalent anioins such as
perchlorate (ClO 4 – ),
pertechnetate
(TcO 4 – ), thiocyanate (SCN – )
MOA: block uptake of iodide by the gland through competitive inhibition of the
iodide transport mechanism.

11. Adverse effect
They include swollen salivary glands, mucous membrane ulcerations,
conjunctivitis, rhinorrhea, fever, metallic taste, bleeding disorders, and rarely,
anaphylactoid reactions.
THERAPEUTIC USES
The antithyroid drugs are used as definitive treatment of hyperthyroidism, to control
the disorder in anticipation of a spontaneous remission in Graves’ disease.
Iodide salts are used in thyroid storm(severe thyrotoxicosis) & to prepare the
patient for surgical resections of the hyperactive thyroid.

12. THANK YOU