2. Introduction
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⚫ Thyroid gland is one of the largest and highly vascularized
endocrine gland present in the body.
⚫ It is made up of functional units called follicles or acinus.
⚫ Follicles contain a cavity known as follicle lumen that is filled with
gelatinous colloid is surrounded by a single layer of epithelial cells.
⚫ A glycoprotein known as thyroglobulin is a protein of high
molecular weight that binds the iodine present in organic form.
⚫ Upon hydrolysis thyroglobulin releases thyroid hormones which
are considered to be iodinated tyrosine derivatives a they are
considered from l-tyrosine.
3. Biosynthesis of Iodine :-
1. Iodine Trapping:
⚫ The thyroid follicular cells trap the plasma iodine against a
concentration gradient of 25:1 between the thyroid follicular cells
and plasma.
⚫ The iodine is taken up by sodium or I- symporter.
⚫ This process is stimulated by thyroid stimulating hormone (TSH)
and inhibited by certain inorganic ions like thiocyanates,
perchlorates etc.
2. Oxidation and Iodination:
⚫ Iodine trapped by follicular cells is oxidized to hypoiodate under the
influence of H2O2 and thyroid peroxide.
⚫ Hyoiodate binds to tyrosin residues of thyroglobulin molecules and
form monoiodotyrosine (MIT) and diiodotyroine (DIT).
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4. 3. Coupling:
⚫ One DIT molecule is coupled with one MIT molecule to form T3 or
two DIT molecules couple with each other to form T4.
⚫ Coupling is an oxidative process catalyzed by thyroid peroxidase
and is stimulated by TSH.
4. Secretion:
⚫ T3 and T4 bound to thyroglobulin (TG) are taken up from the colloid
material into the follicular cells endocytosis.
⚫ Lysosomal proteases act on the intracellular TG and releases T3, T4
MIT and DIT.
⚫ T3 and T4 directly enters into the circulation while MIT and DIT are
deiodinated and the iodine thus removed re-enters the cycle.
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5. 5. Peripheral conversion of T4 to T3:
⚫ T3 is principle hormone and physiologically more active, but is
formed in lesser amounts than T4 converted to T3 (active form) in
the peripheral tissues especially liver and kidney.
⚫ This process is inhibited by drugs such as propranolol,
glucocorticoids and propyithiouracil.
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6. Differences between T3 and T4
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T3 T4
1. Quicker on set of action (6-8 hours) 1. Delayed on set of action (6-8 hours)
2. Shorter plasma half-life (t1/2- 1-2
days)
2. Longer plasma half-life (t1/2- 6-7
days)
3. Effective in small doses 3. Effective in large doses
4. less tightly bound to plasma proteins 4. More tightly bound to plasma proteins
5. Highly bound to nuclear receptors 5. Less bound to nuclear receptors
7. Thyroid Diseases are of two types
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Hypothyroidism Hyperthyroidism
Hypothyroidism is when the thyroid gland does
not produce enough thyroid hormones to meet
the needs of the body. The thyroid is
underactive
Hyperthyroidism (excessive thyroid
hormone) is a condition in which there is
an excessive amount of thyroid hormones.
Symptoms Symptoms
Fatigue, weight gain, cold intolerance restlessness, agitation, anxiety,
slowed heart rate, movements, speech, tremors, weight loss despite
joint and muscle pain, cramps, weakness, an increased appetite, sweating,
constipation, dry skin, thin, brittle hair or rapid heart rate, intolerance to heat,
fingernails, decreased sweating, pins and
needles, heavy periods, or menorrhagia,
and frequent bowel movements,
nervousness, skin thinning
weakness, high cholesterol, puffy face, feet,
and hands, insomnia, balance and co-
ordination issues, loss of libido, recurrent
urinary and respiratory tract infections,
anemia, depression, hoarseness, puffiness in
the face, thinned or missing eyebrows, slow
heart rate, hearing loss, poor growth,
delayed development of teeth, poor mental
development, delayed puberty
9. ⚫ Thyroid Drugs are used to correct hypothyroidism. Various Thyroid
Drugs employed include levothyroxine (L-Thyroxine),
Levothyronine (L-Thyronine), Liotrix and dessicated thyroid gland
and thyroglobulin.
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Mechanism of action:
⚫ Thyroid hormones diffuse across the cell membrane and bind into
intracellular thyroid receptors.
⚫ After penetrating into the cell T4 gets converted to T3 which as more
affinity for the thyroid receptors.
.
11. Therapeutic Uses:
⚫ L-thyroxine oral tablet is used to treat hypothyroidism. This is a
condition when your thyroid gland produces too little thyroid
hormone.
⚫ L-thyroxine also can be used to treat goiter, which is an enlarged
thyroid gland. It also treats certain types of thyroid cancer
Dose:
0.05 -0.2 μg OD on an empty stomach
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13. Therapeutic Uses:
⚫ It is used to treat hypothyroidism.
⚫ It is also used in special situations like myxeoedema, Myxoedema
coma, and thyroid cancer.
Dose:
It is given in a dose of 20μg 1-3 times/day
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15. ⚫ Antithyroid Drugs are used to suppress hyperactive thyroid gland.
Thyrotoxicosis occurs due to excessive production of T3 and T4 by
the thyroid gland.
⚫ Grave’s disease is an autoimmune disorder characterized by
production of thyroid stimulating immunoglobulins. These
antibodies produces TSH-like effects but are not regulated by
negative feedback mechanism. As a results TSH is produced in
excessive amounts to produce T3 and T4. Enlarged thyroid gland
and exopthalmous are its characteristics sign.
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18. Adverse Drug Reactions:
⚫ Over treatment with thioamides causes reversible hypothyroidism
and goiter.
⚫ They commonly cause GI intolerance, joint pains, and skin rashes.
⚫ Hair loss, dysgeusia, fever, hepatic damage and agranulocytosis
may occur but rarely.
Therapeutic Uses:
⚫ Thioamides are used to control Thyrotoxicosis seen in Grave’s
diseases as well as in toxic nodular goiter.
⚫ Carbimazole is given in young patients with florid hyperthyroidism
and substantial goiters to render them euthroid.
⚫ Elderly patients who are treated with are initially treated with
Antithyroid drugs which are then gradually withdrawn when
response to develops.
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20. Therapeutic Uses:
⚫ It is used to treat overactive thyroid (hyperthyroidism). It works by
stopping the thyroid gland from making too much thyroid hormone.
⚫ This medication is not recommended for use in children.
Dose:
⚫ Propylthiouracil (Propylthiouracil tablet) is administered orally.
The total daily dosage is usually given in 3 equal doses at
approximately 8-hour intervals.
⚫ Adults:
The initial dose is 300 mg daily. In patients with severe hyper-
thyroidism, very large goiters, or both, the beginning dosage usually
should be 400 mg daily, an occasional patient will require 600 to
900 mg/day initially. The usual maintenance dosage is 100 to 150
mg daily.
⚫ Pediatric Patients:
For children 6 to 10 years of age, the initial dosage is 50 to 150 mg
daily. For pediatric patients 10 years and over, the initial dosage is
150 to 300 mg daily. The maintenance dosage is determined by the
response of the patient.
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22. Adverse Drug Reactions:
⚫ stomach upset,
⚫ nausea,
⚫ vomiting,
⚫ mild skin rash/itching,
⚫ headache, drowsiness,
⚫ dizziness,
⚫ muscle/joint/nerve pain,
⚫ swelling, or
⚫ Hair loss.
Therapeutic Uses:
⚫ It is used to treat overactive thyroid (hyperthyroidism). It works by
stopping the thyroid gland from making too much thyroid hormone.
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23. Reference books
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⚫ Text book of Medicinal chemistry volume-1-3rd edition by
V.Alagarasamy.
⚫ Text book of Medicinal chemistry volume-2-3rd edition by
V.Alagarasamy.
⚫ Medicinal chemistry by Rama Rao Nadendla.
⚫ Faye’s Principles of Medicinal Chemistry- 7th edition by Thoms
L.Lemke, Victoria F.Roche, S. Willam Zito.
⚫ Medicinal and Pharmaceutical Chemistry by Harkishan Singh, V.K
Kapoor.
