This is a presentation of Thyroid Drugs for b pharmacy 5th-semester students under the syllabus prescribed by PCI

1. TOPICS TO DISCUSS
1. INTRODUCTION
2. SYNTHESIS, STORAGE AND RELEASE
3. MECHANISM OF ACTION
4. USES
5. INDIVIDUAL HORMONES(STRUCTURE AND
USES)
BY:- SIFATJOT SINGH CHADHA
(B.PHARMACY 5TH SEMESTER)
Thyroid Drugs

2. INTRODUCTION
1. Thyroid is a bilobed gland
situated in the neck region that
produces main 2 types of
hormones
 Thyroxin(T4)
 Tri-iodothyronine(T3)
1. T4 is the major type of thyroid
hormone but T3 is more potent
2. T4 is converted to T3 with
deiodenases enzyme which
further undergo
decarboxylation and
deiodination to form Iodo-
thyronamine and thyronamine
3. The receptors for thyroid
hormones are intracellular
DNA binding proteins

3. Synthesis of Thyroid hormones
 It involve the following steps
1) Uptake of plasma iodide by follicle cells
2) Oxidation of Iodide and iodination of tyrosine
residues of thyroglobin
3) Coupling
4) Secretion of thyroid hormone
5) Peripheral conversion of T4 to T3

4. Uptake of Iodide by follicle cells
 An energy-dependent active process allows the
follicle cells to take up the circulating iodide. The
TSH stimulates this uptake, which also depends on
thyroid iodine concentration. The uptake is
stimulated in iodine deficient state and is delayed in
the presence of high amounts of thyroid iodine

5. Oxidation of Iodide and iodination of
tyrosine residues of thyroglobin
 The iodide oxidizes into iodine atom or free radical (I
0 ) in the follicle cells by thyroperoxidase enzyme
that needs H2O2 (oxidising agent).
 Tyrosine residues of thyroglobulin undergo
iodination in the presence of thyroperoxidase
enzyme and form iodotyrosine and then
monoidotyrosine (MIT) and diiodotyrosine (DIT).
 Iodotyrosine molecules undergo coupling to produce
T 3 (MIT+DIT) or T4 (2 molecules of DIT) in the
presence of thyroperoxidase enzyme. The iodinated
thyroglobulin is released and stored in the follicular
lumen and this is called coupling reaction.

6. Secretion of Thyroid hormone
 The iodinated thyroglobulin is taken back by the
follicle cells by endocytosis in the presence of
thyrotropin. In the process of endocytosis, the follicle
cells engulf some amount of the thyroglobulin
colloid, which is acted upon by proteolytic enzymes
to release thyroid hormones in the bloodstream.

7. Metabolism of Thyroid Hormones
 Thyroid hormones are deiod inated in the liver and
kidney or other peripheral organs , deaminated, and
partially conjugated . A part of T 4 is deiodinated
into active T 3 or reverse T 3 (rT3 ).

9. Uses of Thyroid Hormones
 Thyroid hormones have the following uses:
 1) Hypothyroidism (Myxoedema): They are used for lifetime to treat t his
condition.
 2) Hypothyroid Coma: It is an emergency condition in which the thyroid
activity needs to be restored rapidly. L-thyroxine (500 g) is administered
intravenously followed by a daily maintenance dose after a week. Then again,
liothyronine (5-10 g) is administered via orogastric tube after every 8 hours,
followed by maintenance therapy after recovery. Many patients are
administered with hydrocortisone through intravenous route due to related
hypoadrenal state.
 3) Cretinism: The symptoms can be subdued if thyroid therapy is started as
soon as the hypothyroid infant is born . L-thyroxine is given in 25 g dose to
infants below one year of age, and after every 6 months the dose is increased
by 12.5 -25 g followed by maintenance dose of 6 -8 g/kg/day. A higher
initial dose of 50 g is given to children above one year of age.
 4) Goitre: Thyroid hormones are required in simple and nodular goitre with
thyroxine deficiency. Carcinoma has to be ruled out. Usual maintenance
doses are used.

10. Mechanismof Actionof ThyroidHormones
T4 and T3 penetrate by active transport
Combine Nuclear Thyroid hormone receptor (Receptor is
steroidal)
Hormone Receptor complex bind to DNA via Zinc fingers undergo
conformation change
Causes Gene Transcription
Production of specific m-RNA and protein synthesis
Gives Various metabolic and anatomical effect(Tachycardia, Arrhythemia, Increased blood pressure)

11. INDIVIDUAL THYROID HORMONES
 In the syllabus of Medicinal Chemistry-II we have
only 2 hormones that are as follows:-
1. L-Thyroxine
2. L-Thyronine

12. L-Thyroxine
 Uses:-
 It is used either alone or
with anti -thyroid drugs for
treating hypothyroidism,
goitre, chronic lymphocytic
thyroiditis, myxoedema,
coma,
 L-Thyroxine (or
levothyroxine) is the major
hormone produced by the th
yroid gland. It is synthesised
in the thyroglobulin by the
iodination of tyrosine
(monoiodotyrosine) an d
coupling of iodotyrosine
(diiodotyrosine)

13. L-Thyronine
 Uses
 It is used as a replacement therapy
in primary (thyroidal), secondary
(pituitary), and tertiary
(hypothalamic) congenital or
acquired hypothyroidism.
 It is used as an adjunct to surgery
and radioiodine in thyroid cancer.
 It is used as a diagnostic agent in
suppression tests for mild
hyperthyroidism or thyroid gland
autonomy
1. L-Thyronine (or l iothyronine or
T 3 ) is a thyroidal hormone. It is
synthesised by the thyroid gland
in a ratio of 4:1 as compared with
T 4:T3. L-Thyronine is the active
form of thyroxine, and has
tyrosine bound with iodine in its
basic chemical structure