Pharmacology of antithyroid drugs Radioactive iodine advantages and disadvantages Propylthioyracil Methimazole Carbimazole Treatment of thyroid storm

1. Dr. Netravathi
Asst. Professor
J.N. Medical College
Belagavi
Thyroid and Antithyroid drugs

2. Thyroid hormone
 The thyroid gland secretes 3 hormones-
 Thyroxine(T4)
 Triiodothyronine (T3)
 Calcitonin.
 The thyroid hormones are synthesized and stored
in the thyroid follicles as a part of thyroglobulin
molecule – which is a glycoprotein synthesized by
thyroid cells.

3. Thyroid hormone
 All are amino acid derivatives (tyrosine), but are
hydrophobic molecules
 Can freely cross the cell membrane
 Transported in circulation bound to specific
protein carriers
 Bind to intracellular receptors on target tissues
 Synthesis accomplished via iodination of tyrosine
residues on thyroglobulin in iodide cycle
 All aspects of hormone synthesis are regulated
by extra
thyroid mechansims (TRH-TSH)

4. The main steps involved in the
synthesis and storage of Thyroid
hormone
1. Iodine uptake : about 1/5 th of body’s iodine is
in the thyroids . Uptake in the thyroid gland is
stimulated by TSH hormone.
2. Oxidation and iodination : iodide trapped by
follicular cells is oxidized by thyroid peroxidase
enzyme to iodinium ions . These forms are
combined with tyrosil residues of thyroglobulin
to form –
- MIT ( monoiodotyrosine)
- DIT ( diiodotyrosine)

5. 3) Coupling : pairs of iodinated tyrosil residues
couple together to form T3 ,T4 ( T4 more than
T3)
coupling is an oxidative reaction and is
catalysed by the same thyroid peroxidase.
4) Storage and release : stored in the thyroid
follicles as thyroid colloid .
- normal human thyroid secretes 60-90 micro
gms of T4 and 10-30 micro gms of T3 daily.

6. 1.
2.
3.
4.

7.  Thyroid secretes more T4 than T3 , but in iodine
deficient state this difference is reduced.
 • T4 is the major circulating hormone
 Peripheral conversion of T4 to T3 occurs especially
in liver, kidney.
 T3 has approximately 15 times potency of T4
 Plasma t1/2 : T4= 6-7 days and T3= 1-2 days
 Preparation : l-thyroxine sodium , 25 - 100 micro
gms
 It should be administered in empty stomach to avoid

8. MOA

9. Actions
 Growth and development: T3 and T4 are essential
for growth and development , it is by control of
protein synthesis in the translation of genetic code.
 Metabolism :
Lipid – enhance lipolysis by potentiating the action
of catecholamines .
Carbohydrates – metabolism is stimulated ,
hyperglycaemia and diabetic like state is seen.
Protein – catabolic effect, increased amount of
protein being used as energy source.

10. Other actions
 CVS: heart rate , contractility and output are
increased .
- stimulate heart by direct effect, increased Ca+
ATPase activity and At least partly due to increased
sensitivity to
catecholamines
 Increased milk production in lactation
 Calcium mobilization from bone
 Necessary for normal menstrual cycles and fertility

11. Uses
 The most important use of thyroid hormone is for
replacement therapy in deficiency states.
 Cretinism
 Adult hypothyroidism
 Myxoedema coma
 Non toxic goiter
 Thyroid nodule
 Papillary carcinoma of thyroid

12. They are the drugs to lower the
functional
capacity of the hyperactive thyroid
gland
Thyroid inhibitors

13. Classification

14. MECHANISM OF ACTION
 ANTITHYROID DRUGS : bind to thyroid
peroxidase and prevent oxidation of iodide or
iodotyrosyl residues
1) inhibit iodination of tyrosine residues in
thyroglobulin
2) inhibit coupling of iodotyrosine residues to
form T3 T4.
Thyroid colloid is depleted
over time and blood levels
of T3/T4 are reduced.

15.  Effective in the long-term treatment of
hyperthyroidism.
 6-8 weeks before maximum effect of the drug
achieved. Drug inhibits hormone synthesis, so
hormones synthesized prior to drug use will
continue to cause hyperthyroid condition.
 Typical side effects include headache, nausea,

16.  Serious liver damage, decreased red and
white blood cell synthesis, as well as
decreased platelet production have been
reported in a few cases. The drug’s
interaction with other enzymes responsible for
clotting factor synthesis accounts for some of
these serious side effects.
 Administering too high a dosage of anti-
thyroid drugs can cause hypothyroidism

17.  Preparations and dose :
Propyl thiouracil : 50-150mg TDS followed by
25-50mg BD/ TDS
Methimazole : 5-10mg TDS
Carbimazole : 5-15 mg TDS

18. Uses
 Grave’s disease
 Toxic nodular goiter
 Advantages of antithyroid drugs over surgery :
1) no surgical risks
2) hypothyroidism if induced is reversible
3) can be used even in children and young adults
 During pregnancy : low doses of Propylthiouracil
is indicated

19. Iodine and iodide
 It is the fastest acting thyroid inhibitor
 The gland if enlarged shrinks becomes firm and
less vascular
 It will stop the release of hormones from the
gland, called as “thyroid constipation”.
 Excess iodide inhibits its own transport in thyroid
cell and may alter redox potential of the cells ,
thus interfering with iodination  reduced T3 T4
synthesis.
 Peak effects are seen in 10-15 days

20.  Preparations and dose : Lugol’s solution ( 5%
iodine in 10% Pot. Iodide solution )
 Iodide (sodium/ potassium) 100-300mg /day
 USES :
1) preoperative preparation
2) thyroid strom
3) prophylaxis of endemic goiter
4) as antiseptic

21. Radioactive iodine
 I131 emits Xrays as well as beta particles .
 The beta particles are utilized for their destructive
effect on thyroid cells
 The beta particles penetrates only 0.5- 2mm of
tissue . The thyroid follicular cells are effected
from within , under goes pyknosis, and necrosis
and followed by fibrosis , without damaging the
neighbouring tissues .
 Dose : 25-100 micro curie

22. Advantages
 1) treatment is simple, inexpensive
 2) no surgical risk
 3) cure is permanent
 DISADVANTAGES :
 1) hypothyroidism
 2) long latent period of response
 3) contraindicated in pregnancy
 4) not suitable for young patients ( only after 25 yr
of age)

23. Thank you ….