The document summarizes thyroid hormones and anti-thyroid drugs. It discusses the synthesis, storage, and secretion of thyroid hormones including the uptake of iodide, oxidation and iodination of tyrosine residues, and the coupling reaction to form T3 and T4. It also describes the actions of thyroid hormones and their mechanisms of action by binding to nuclear receptors and regulating gene transcription. The document then summarizes the classes of anti-thyroid drugs including those that inhibit hormone synthesis like propylthiouracil and methimazole, as well as iodine/iodide which can inhibit iodide uptake and hormone release. The uses and mechanisms of these anti-thyroid drugs for conditions like Graves'

1. Thyroid and
Anti-thyroid drugs
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Miss Snehal S. Chakorkar (M.pharm)
Dept Of Pharmacology,

2. Introduction
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Thyroid gland secrets 3 main
hormones:
⚫ Thyroxine (T4)
⚫ Triidothyronine
(T3)
Important for
growth and
development
Both considered
as thyroid
hormone
⚫ Calcitonine - Important for control of plasma Ca2+.
Functional unit of thyroid –
Follicle or acinus – structure of
flollicle is cavity surrounded by
epithelial cell.- filled with thick
colloid – called thymoglobulin (
Large glycoprotein).
Thyroglobuline molecule contains 115 tyrosin residue.
Follicle have high blood supply.

3. Synthesis , storage & secretion of thyroid hormone:
Involve following steps;
1)Uptake of plasma iodide by follicle cells.
5- 3
2)Oxidation of iodide & iodination of tyrosin residues of
thyroglobuline.
3) Coupling.
4)Secretion of thyroid hormone.
5)Peripheral conversion of T4 to
T3.
1)Uptake of plasma iodide by follicle cells:
Regular I2requirement of body is 30-50mg which fulfilled by
food & water, about 1/5 is present in thyroid.
Iodide is capture from blood & move to lumen by 2 transporter,
Na+/I- symporter (NIS)- Locate at basolateral surface of
thyrocytes. Pendrin I-/Cl- Porter(
PDS)-At apical membrane.
Iodine uptake is energy dependent process energy

4. 2)Oxidation of iodide & iodination of tyrosin residues
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Iodide
Thyroid peroxidase
enzyme
Iodinium(I+)/
Hypoiodous acid (HOI)/
Enzyme linked hypoiodate
(E-OI)
Bind to tyrosil residue
of
thyroglobuline
Monoiodotyrosin (3rdposition)
Diiodotyrosin (5th position)
of thyroglobuline.
Captured Iodide carried across the membrane by pendrine
transport & oxidised by thyroid peroxidase enzyme (Oxidising
agent).
TSH

5. 3) Coupling:
Coupling is oxidative reaction catalyzed by same thyroid peroxidase
enzyme .
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Thyroglobuline is efficient protein helps for reaction.
Pair of iodinated tyrosil residue couple together to form T3 &
T4. 2 molecule of diiodotyrosine-=Thyroxine (T4)
1 molecule of monoiodotyrosine + 1 molecule of diiodotyrosine
= Triidothyronine (T3).

6. 4)Secretion of thyroid hormone:
Normal human thyroid secretes- 60-90 μg of T4 & 10-30 μg of T3.
The iodinated residue of thyrosin get transferred to the interior of the
follicles where it store as thyroid colloid.
5- 6
After release it uptake by endocytosis after stimulation of TSH.
5)Peripheral conversion of T4 to T3:
Peripheral tissue like liver, kidney convert T4 to T3.
Target tissue take T3 from plasma depended upon their metabolic
need. While brain and pituitary takes T4 and convert that to T3
with own cell.
Drugs like some propylthiouracil inhibit conversion of T4 to T3.

7. Actions:
The T3 & T4 having almost having same functions ;
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1) Growth & Development.
2) Intermediary
metabolism.
3)Calorigenesis.
4)Cardivascular system.
5) Nervous system.
6)Skeletal
muscle. 7)GIT.
8)Kidney.
9)Haemopoiesis
.
10) Reproduction.
Ref: https://www.cleanpng.com/png-
thyroid- hormones-thyroid-nodule-

8. 1) Growth & Development.
Eessential for normal growth and development.
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The most remarkable action is metamorphosis of tadpole to frog: the
tail is used-up to build lungs, limbs and other organs.
The action cannot be categorised as catabolic or anabolic.
T3 & T4 have role in protein synthesis i.e. translation of genetic
code therefore Congenital deficiency of T, and T, resulting in
cretinism & delayed development of organs or deficit dendrites
ramification, synapse formation & impaired myelination.
2) Intermediary metabolism. Thyroid hormones have
marked effect on Thyroid lipid, carbohydrate and protein
metabolism.
Lipid: T3 & T4 potentiate action of catecholamine & lipolytic
action (Increases lipolysis)
Suppress phosphodiestrase- Increases cAMP- Increases plasma free
fatty acid.
Increases cholesterol metabolism- so causes hypocholesterolemia.

9. Carbohydrate: T3 & T4
Increases carbohydrate metabolism.
Increases sugar utilization by tissue but faster absorption of
glucose from blood. Increases absorption & less metabolism
causes hyperglycemia & diabetic like state.
Therefore hyperthyroidism causes insulin resistance.
Protein: T3 & T4
Increases synthesis of certain protein which used as protein
source by
body.
But prolong action causes negative nitrogen balance & weight
loss. At low concentration of T3 & T4 inhibit mucoprotein
synthesis .
T3 & T4 increses the oxygen consumption & heat production.
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10. 3)Calorigenesis:
T3 & T4 increases basal metabolic rate by increasing cellular metabolism.
Which helps to maintain body temperature during calorigenesis causes
oxidative phosphorylation & that release heat but this reaction only
occurs in high dose.
4)Cardivascular system:
T3 & T4 causes hyperdynamic state of circulation Increses blood
volume unknowingly).
Also increases heart rate, contractility & output of heart by acting on
contractile
element.
During hyperthyroidism causes arterial fibrillation & other regularity like
CHF and angina.
5) Nervous system:
T3 & T4 deficency causes mental retardation or cretinism.Also
hyperthyroid individuals are anxious, nervous, excitable or produces
tremors. 5- 1

11. 6)Skeletal muscle:
Hypothyroidism causes swelling of skin & underlying tissue.
Hyperthyroidism causes increases muscle tone, tremor & weakness.
7)GIT:
T3 & T4 causes increased gut activity which causes diarrhea.
8)Kidney:
Hypothyroidism causes diuresis . While normal person not causes
diuresis.
9)Haemopoiesis:
T4 increases process of RBC formation (Erythropoiesis)
Therefore T4 treatment given to patient suffering from anemia.
10) Reproduction:
Thyroid has an indirect effect on reproduction fertility is impaired
in hypothyroidism & Oligomenorrhoea(Infrequent menstrual
periods).
Normal thyroid function is required for maintenance of pregnancy
lactation
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12. Mechanism Of Action:
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T3 & T4 penetrate cell by active transport
Combine nnuclear thyroid hormone receptor (TR) ( Receptor is
steroid & retinoid superfamilly)
T3 has 15 – fold higher binding to TR receptor than T4.
Hormone receptor complex bind to DNA via zinc fingers undergo
conformational changes
Causes gene transcription
Production of specific m-RNA & protein synthesis
Gives various metabolic & anatomic effect ( like Tachycardia,
Arrhythmia, Increased blood pressure hyperglycemia.)

13. Relation between T4 & T3:
1) Normally T4 more secrete than T3- but in iodine deficiency this
deference decreases.
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2) T4 15 times more tightly bound to plasma protein.
3) T3 is 5 times more potent than T4 & acts faster peak effect T3
in 1- 2days, T4 in 6-8 days.
4) About 1/3 of T4 will convert in T3.
Preparations:
1-Thyroxine more preferred than 1-Thyronine.

14. Uses:
The most important uses of thyroid hormone are
as replacement therapy deficiency states:
1)Cretinism
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2)Adult
hypothyroidism
3)Myxoedema coma
4)Nontoxic goiter
5) Thyroid nodule
6) Papillary carcinoma of
thyroid.
7) Other uses.

15. 1)Cretinism:
Caused due to failure of thyroid development (sporadic cretinism).
Due to extreme iodine deficiency (endemic cretinism).
Mostly during infancy or childhood.
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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.

16. 3)Myxoedema coma:
It is an emergency condition were progressive mental deterioration
caused due to deficient production of thyroid hormone
( Hypothyroidism).
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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.

17. 5) Thyroid nodule:
When T4 treatment is started TSH synthesis get suppressed causes
normal functioning of nodules function while nonfunctional
nodules not respond.
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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.

18. A) Anti-thyroid drugs/ Thyroid
inhibitors:
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Definition: “ These are the pharmacological agents which are
used to lower the functional capacity of hyperactive
thyroid gland”
These are the agents used in treatment of thyrotoxicosis ( It is
excess secretion of thyroid hormone due to disorders; like
⚫ Graves disease( auto immune disease)
⚫ Toxic nodular goiter.
Classification:
1)Inhibit hormone synthesis (Antithyroid
drugs):
Ex-Pronylthioumcil Methimazole,
Carbimazole.
2) Inhibit iodide trapping( Ionic
inhibitors): Ex-Thiocynates, Perchlorate,
Nitrates.
3) Inhibit homone release:
Ex-lodine, lodides of Na and K, Organic
iodide.
1 & 2 class
called as
Goiterogen.
If dose
increases
causes
enlargement of
thyroid.
By feedback
release of
TSH

19. 1) Antithyroid drugs: (
Thioamides)
Hormone synthesis inhibitors called Antithyroid drugs.
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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 iodination of tyrosine residues in thyroglobuline.
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
1st diabetes mellitus- but methamizole & Carbamazole not
have this action.

20. Adverse drug reaction:
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1)Hypothyroidism and goiter – Due to over treatment-
After stopping of treatment reversible effect is
observed.
At normal dose goiter not develop because T4
concentration
which maintain TSH level normal.
High does: Causes excess TSH production- Enlargement
of thyroid gland (Goiter).
2)Other side effects: GI intolerance, Skin rashes, joint pain.
3)Graying or loss of hair, loss of taste, fever & liver
damage.
4) Agranulocytosis & Jaundice may occurs.
Preparation:
Propylthiouracil(50mg-150mg TDS)
Methimazole (5-10mg)

21. Use
s:
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1)Control thyrotoxicosis in graves disease & toxic nodular goiter.
Some times patient take another treatment like cough
preparation, contrast media, aminodarone- less responsive to
Antithyroid agent.
In those cases the dose should be modify depending on the patient.
As definitive therapy: In some patient after 1-2 year of
treatment remission may occur.
After drug withdrawal if symptoms recur again start the treatment.
Above situation mostly occurs in patient having short history of
graves disease & small goiter.
The case like nodular goitre remission are rare or toxic that time
surgery or I 131 is preferred.
Some cases in elderly patient with multinodular goiter maintenance
therapy causes less responsive to I131 so surgery advised.

22. 2) Preoperatively:
Surgery (thyroidectomy) is advised to thyrotoxicosis
patients which is very risky so preoperative treatment of
carbimazole is given.
3) Treatment along with I131:
When there is prompt control of severe hyperthyroidism in
older patient following sequence of therapy employed;
Starting treatment withAntithyroid drug.
1-2 week gap.
Radioiodine
dosing.
AgainAntithyroid drug after 5-7
days. Withdrawal of drug after 3
month.
Again start I131 treatment. 5- 2

23. Advantages ofAntithyroid drug over surgery / I131 treatment:
No surgical risk, scar or chances of injury
to parathyroid or nearest laryngeal
nerve.
If treatment withAntithyroid shows side effect like
hypothyroidism then stoppage of treatment reverse the
action.
TheAntithyroid drugs used for children as well as young
adults.
Disadvantage:
Prolonged (often life long) treatment is needed because
stoppage of
treatment shows recurrence & relapse rate is high.
Not practicable in uncooperative/unintelligent
patient. High drug toxicity & side effects.
During pregnancy thyroidectomy and I131 are
contraindicated because it develops risk of foetal
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24. B)
Iodine/Iodide
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Even if the iodine is one of the constitute of thyroid hormone
but still it acts as faster acting thyroid
inhibitor(Antithyroid).
In the process of thyroid hormone release in one step iodine is
covered in to on vivo iodide (I-) and due to negative
feedback mechanism iodide inhibit release of thyroid
hormone.
Within 1-2 days of starting of treatment causes inhibition of
secretion of thyroid hormone while 10-14 days causes
marked reduction in vascularity of gland & which causes
decreases the size of gland.
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.

25. Mechanism of action:
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Actual mechanism is unknown;
It inhibits own transport in to thyroid cell ( Step 1 in thyroid
synthesis) by acting on NIS (Sodium Iodide symporter)
It attenuates TSH & cAMP& causes thyroid inhibition.
Also excess iodide rapidly interferes with tyrosil ( Iodination
step2) Inhibit thyroid ( Wolff chaikoff effect)
Inhibition of hormone release causes thyroid constipation.

26. Use
s:
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1) Preoperative preparation:
For thyroidectomy in graves disease; iodine for 10 days before
surgery will given which makes gland less vascular & easier to
remove by
operation.
2) Thyroid storm:
Lugol's iodine (6-10 drops) or iodine containing radiocontrast
media (iopanoic acid) are used orally to stop further release and
conversion of T3/T4 from the thyroid.
3) Prophylaxis of endemic goiter: It is used as "iodized salt“.
4)Antiseptic: The tincture of iodine, povidone iodine is used
as antiseptic.

27. Adverse drug
reaction:
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1) AcuteAcute reaction It occurs in sensitive people.
Shows symptoms like swelling of lips, eyelids, angio- edema of
larynx (may be dangerous), fever, joint pain, petechial
haemorrhages, thrombocytopenia, lymphadenopathy.
2) Chronic overdose (iodism):
Inflammation of mucous membranes, salivation, rhinorrhoea,
sneezing, lacrimation, swelling of eyelids, burning sensation in
mouth, headache, rashes, g.i. symptoms.
3) Long-term use of high doses can cause hypothyroidism & goiter.
4) If high dose given to pregnant women chance to
hypothyroidism & goiter in foetus.

28. C) Radioactive
Iodine:
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Ex- I131, I123 I125.
The stable form of isotope of iodine is I127 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).

29. Mechanism of action:
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The isotope emits both
beta (β) & gama (δ) radiation
Have shorter range
Pass through tissue
without damage
Penetrate tissue
(up to 0.5-2 mm)
Pyknosis & necrosis
with fibrosis

30. Therapeuti
c:
The hyperthyroidism is mainly occurs due to grave’s disease or
toxic nodular goiter at that time therapeutic dose is 3-6 mg
curie.
High dose is requirement for toxic multinodular goiter.
The response to radio active iodine is start after 2 week & get
increased
after 3 month.
Advantages:
Treatment with I 131 is inexpensive.
No surgical risk, scar or thyroids/recurrent laryngeal nerves after
treatment with I 131
Once hyperthyroidism is controlled, cure is permanently.
Disadvantages:
1) Hypothyroidism: About 5-10% patients of Graves' disease treated
with 1311 become hypothyroid.
2) Very slow response was observed for treatment with I131.
3) during pregnancy drug is Contraindicated because it causes
foetal thyroid destruction.
4)I131 not suitable for young patients more likely to develop
hypothyroidism& genetic damage/cancer5-
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31. D) β- Adrenergic
blocker:
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Nonselective B blockers- propranolol used for tretment of
thyrotoxicosis because in hyperthyroidism; over activity of
sympathetic nervous system was observed i.e. palpitation, tremor,
nervousness, myopath, swelling.
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 I131 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.

32. Reference:
⚫ Rang H.P. and Dale M.M.: Pharmacology, Churchill
Livingstone, Edinbergh.
⚫ Katzung B.G.: Basic and Clinical Pharmacology, Lange
 Medical Publications, California.
⚫ Craig C.R. and Stitzel R.E.: Modern Pharmacology, Little Brown
and Co., Boston.
⚫ Bowman W.C. and Rand M.J.: Textbook of Pharmacology,
 Blackwell Scientific Publications, Oxford.
⚫ P.N Bennett & M J Brown: Clinical Pharmacology, Churchill
Livingstone, Edinburgh.
⚫ Tripathi K.D.: Essentials of Medical Pharmacology, Jaypee
 Brothers, Medical Publishers, New Delhi.
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