The content of presentation is as follows - introduction to thyroid - thyroid hormone synthesis - type of thyroidism - difference between hyperthyroidism and hypothyroidism -treatment of hypothyroidism - anti thyroid drug classification - mechanism of anti thyroid drugs -

1. z
Anti – Thyroid Drugs
Prepared by-
Tasnim Baldiwala
M.Pharm (Pharmacology)
Semester - II

2. z
Content
 Introduction to thyroid hormone
 Thyroid hormone synthesis
 Pharmacological action of thyroid hormone .
 Types of thyroidism
 Difference between hyperthyroidism and hypothyroidism
 Drugs acting on hypothyroidism
 Anti thyroid drugs

3. z
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 .

4. z
Introduction to Thyroid Hormone
 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

5. z
Introduction to Thyroid Hormone
HYPOTHALAMUS
TRH
ANTERIOR PITUITARY GLAND
TSH
THYROID GLAND
SYNTHESIS AND RELEASE
T3 AND T4
+
+
-
-

6. z
THYROID HORMONE SYNTHESIS
 The synthesis of thyroid hormone includes following steps
• IODINE TRAPPING
• OXIDATION AND IODINATION
• COUPLING
• HORMONE RELEASE
• PERIPHERAL CONVERSION OF T3 and T4

7. z THYROID HORMONE SYNTHESIS
1.IODINE TRAPPING :
 Active transport of iodine ions into follicular cells is known as
IODINE TRAPPING .
 This takes place by SODIUM / IODINE SYMPOTERS .
 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 .

8. z THYROID HORMONE SYNTHESIS

9. z
THYROID HORMONE SYNTHESIS
2.OXIDATION AND IODINATION :
Iodide ion Iodine ion
 This formed iodine combine with tyrosine
residues of thyroglobulin molecule to form
monoiodotyrosine (MIT) and diiodotyrosine (DIT).
Peroxidase
enzyme
Oxidation

10. z
THYROID HORMONE SYNTHESIS
3.COUPLING :
 Coupling is the final step in thyroid synthesis of thyroid hormones.
 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.

11. z
THYROID HORMONE SYNTHESIS
4. HORMONE SYNTESIS :
 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 .
5. PERIPHERAL CONVERSION OF T4 TO T3 :
 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.

12. z
Pharmacological action of Thyroid
hormone .
 Metabolic function :
• – CHO metabolism:
o glycogenolysis
o Increase gluconeogenesis
o glucose absorption from GIT
o Enhance glycolysis – rapid uptake of glucose by the cell.
 Net result : blood glucose level
 On protein metabolism: protein catabolism

13. z
Pharmacological action of Thyroid
hormone
 On fat metabolism:
• Increases mobilization of fat,
 On BMR:
• increases BMR
 Growth : increases growth
 On GIT:
• increases appetite & food intake.
• Increases rate of secretion of digestive juice.
• Increases motility of GIT diarrhoea often result in hyperthyroidism

14. z
Pharmacological action of Thyroid
hormone
 On CVS:
• Enhance tissue sensitivity to catecholamines
• increases cardiac output
 • On nervous system:
• excitable effect.
• Has role on development of brain in fetal & 1st few weeks of postnatal life
• Muscle weakness due to protein catabolism

15. z
Disease of Thyroid gland
 Hyperthyroidism/Thyrotoxicosis/Grave’s
disease
 Hypothyroidism –
• Cretinism (in children)
• Myxoedema (in adult)

16. z
Hyperthyroidism v/s hypothyroidism
SR.
NO
SYSTEM HYPERTHYROIDISM
(THYROTOXICOSIS)
HYPOTHYROIDISM
(MYXOEDEMA)
1. METABOLIC Increased basal metabolism rate Decreased basal metabolism
rate
• Lipid decreased cholesterol and
triglycerides
Hypercholesterolaemia and
hypertriglyceridemia
• Carbohydr
ates
Hyperglycaemia Hypoglycaemia
• Proteins -ve nitrogen balance and wasting +ve nitrogen balancing and
weight gain due to accumulation
of mucoproteins
2. CVS • Increased heart rate , stoke
volume , cardiac output
• Decreased peripheral vascular
resistance , high cardiac
output failure , arrhythmias ,
angina
• Decreased heart rate , stroke
volume and cardiac output

17. z
Hyperthyroidism v/s hypothyroidism
SR.
NO
SYSTEM HYPERTHYROIDISM
(THYROTOXICOSIS)
HYPOTHYROIDISM
(MYXOEDEMA)
3. CNS Nervous ness anxiety Lethargy and mental
retardation in cretinism
4. Muscular
skeletal system
weakness , muscle fatigue ,
increased deep tendon reflexes ,
hypercalcaemia, osteoporosis.
Stiffness, muscle fatigue
5 GIT Increased appetite , diarrhoea decreased appetite ,
constipation , ascites
6. Reproductive
system
Menstrual irregularities , decreased
fertility
menorrhagia, infertility ,
decreased libibo , importance ,
oligospermia .
7. Eyes and face Lid retraction , periorbital oedema ,
exophthalmos
Puffy face , large tongue
8. Skin and
appendages
Warm moist , heat intolerance fine
thin hairs
Pale dry skin cold intolerance ,
brittle hair and nails

18. z
Thyroid drugs
 DRUGS
 levothyroxine (L-T4)
 liothyronine (T3)
 liotrix (T4 plus T3)
 All this medication are used as replacement therapy in
hypothyroidism .

19. z
Anti thyroid drugs
Class Drug M.O.A
Thioamides
Carbimazole,
methimazole
Propylthiouracil
Inhibition of thyroxine
synthesis
Anion inhibitors
Perchlorate, thiocyanate Competitive inhibition of
iodine transport
Iodides
Potassium iodide
Sodium iodide
Inhibits organification
and hormone release
Radioactive iodine
Iodine - 131 Destruction of thyroid
parenchyma
β blockers
Propranolol
metoprolol

20. z
Thioamides
 The thioamides methimazole and propylthiouracil are major drugs for
treatment of thyrotoxicosis.
 Methimazole is about ten times more potent than propylthiouracil and is
the drug of choice in adults and children.
 Due to a black box warning about severe hepatitis, propylthiouracil
should be reserved for use during the first trimester of pregnancy, in
thyroid storm, and in those experiencing adverse reactions to
methimazole
 The thioamides act by multiple mechanisms. The major action is to
prevent hormone synthesis by inhibiting the thyroid peroxidase and
blocking iodine organification. In addition, they block coupling of the
iodotyrosine.

21. z
Anion Inhibitors
 Monovalent anions such as perchlorate (ClO 4 – ), and thiocyanate
(SCN – ) can block uptake of iodide by the gland through competitive
inhibition of the iodide transport mechanism.
 Since these effects can be overcome by large doses of iodides, their
effectiveness is somewhat unpredictable.
 The major clinical use for potassium perchlorate is to block thyroidal
reuptake of I – in patients with iodide-induced hyperthyroidism

22. z
Iodides
 Prior to the introduction of the thioamides in the 1940s, iodides were
the major antithyroid agents; today they are rarely used as sole
therapy.
 Iodides have several actions on the thyroid. They inhibit
organification and hormone release and decrease the size and
vascularity of the hyperplastic gland.
 In susceptible individuals, iodides can induce hyperthyroidism (Jod-
Basedow phenomenon) or precipitate hypothyroidism

23. z
Radioactive Iodine
 131 I is the only isotope used for treatment of thyrotoxicosis.
Administered orally in solution as sodium 131 I, it is rapidly
absorbed, concentrated by the thyroid, and incorporated into storage
follicles. Its therapeutic effect depends on emission of β rays with an
effective half-life of 5 days and a penetration range of 400–2000 μm.
Within a few weeks after administration, destruction of the thyroid
parenchyma is evidenced by epithelial swelling and necrosis,
follicular disruption, edema, and leukocyte infiltration.
 Radioactive iodine should not be administered to pregnant women
or nursing mothers, since it crosses the placenta to destroy the fetal
thyroid gland and is excreted in breast milk.

24. z
Beta Blockers
 Beta blockers without intrinsic sympathomimetic activity (eg,
metoprolol, propranolol, atenolol) are effective therapeutic
adjuncts in the management of thyrotoxicosis since many of
these symptoms mimic those associated with sympathetic
stimulation.
 Beta blockers cause clinical improvement of hyperthyroid
symptoms but do not typically alter thyroid hormone levels

25. z
END OF SECTION