Lecture 14

DRUGS TO TREAT THYROID DISORDERS

Phuong-Thuy Thi PHAN, M.S.
 Recommended Reading

1) Thomas L.L., David A.W. (2013). Foye’s Principle of Medicinal

Chemistry 7th edition, Lippincott Williams & Wilkins: Baltimore.
Chapter 29. Thyroid function and thyroid drugs, p.p. 943-963.

2) Lê Minh Trí, Huỳnh Thị Ngọc Phương (2017). Hóa dược 2 (Dùng cho
đào tạo dược sĩ đại học), NXB Giáo Dục Việt Nam. Bài 57. Hormon
tuyến giáp, p.p. 470-482.

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 Goals

1) Know the structures of the active and circulating thyroid hormones

2) Know the mechanism by which the hormone is stored

3) Effect of iodine on thyroid hormone production

4) Know the receptor/ thyroid hormone binding interactions

5) Know the structures of the drugs to treat thyroid disorders

6) Know how the drugs work

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 1. INTRODUCTION TO HORMONE

A hormone is a chemical that is made by specialist cells, usually within

an endocrine gland, and it is released into the bloodstream to send a
message to another part of the body

William Bayliss Ernest Starling

(1860-1924) (1866-1927)

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 1. INTRODUCTION TO HORMONE

"Hormones are substances

secreted from specific cells
and acting on specific
receptors."
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 1. INTRODUCTION TO HORMONE

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 1. INTRODUCTION TO HORMONE

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 1. INTRODUCTION TO HORMONE

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 2.1. THYROID GLAND

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 2.2. THYROID HORMONES

I I I

HO HO HO O
COOH COOH COOH
I H 2N I H 2N I H 2N

monoiodotyrosin (MIT) 3,5-diiodotyrosin (DIT) rT3

I I I

HO O HO O
COOH COOH
I I H 2N I I H 2N

triiodothyronin (T3) thyroxin (T4)

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 2.2. BIOSYNTHESIS OF THYROID HORMONES

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 2.2. BIOSYNTHESIS OF THYROID HORMONES
-
H 2O 2 I +
TPO TPOox TPO-I
NADPH

O O O O
TG NH CH C NH NH CH C OH TG NH CH C NH NH CH C OH
+
CH2 CH2 TPO-I CH2 CH2

I
H
OH OH O OH
H

+
O O TPO-I O O
TG NH CH C NH NH CH C OH TG NH CH C NH NH CH C OH
CH2 CH2 CH2 CH2

I I I
Also
OH OH OH OH
DIT MIT
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 2.2. BIOSYNTHESIS OF THYROID HORMONES

HO O
COOH
s es I I H 2N
a
io din
e
5'd triiodothyronin (T3) - active
I I

HO O
COOH
I I H 2N
I I
thyroxin (T4) 5d
eio
din HO O
as
es COOH
I H 2N
rT3 - inactive

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 2.3. THYROID HORMONE RECEPTOR

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 2.3. EFFECTS OF THYROID HORMONE

• Increases basal metabolic rate

• Increases bone growth
• Potentiates brain development
• Increases heart rate and cardiac output
• Increases catabolism of proteins and carbohydrates

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 2.4. EFFECTS OF IODINE ON TH PRODUCTION

• Diets deficient in iodine will have a higher incompelete

production of T4
• Long term iodine deficiency, thyroglobulin will not contain
sufficient amounts of the hormones to provide sufficient
blood levels
• Great excess of iodine :
o More production of T4 in the thyroglobulin
o Slight increase in circulating T4
o T3 levels remained at physiologically appropriate levels
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 3. DRUGS TO TREAT HYPOTHYROIDISM

• Hypothyroidism is the result of any condition that causes thyroid

hormone deficiency such as:
o Iodine deficiency
o Inflammatory diseases of the thyroid that destroy parts of the gland
o The therapy is to remove the thyroid gland

• Symptoms:
o Goiter
o Cretinism
o Myxedema

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 3. DRUGS TO TREAT HYPOTHYROIDISM

I I I

HO O HO O
COOH COOH
I I H 2N I I H 2N

Levothyroxine (Tynthroid) Triodothyronine (Cytomel)

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 3. DRUGS TO TREAT HYPOTHYROIDISM

outer deiodination
ring inner ring

I I

HO O
COOH
I I H 2N

conjugation ether bond

cleavage oxidative
deamination

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 4. DRUGS TO TREAT HYPERTHYROIDISM

• The increased metabolic rate of hyperthyroidism results in symptoms

opposite to those seen in hypothyroidism.
• Common signs of hyperthyroidism include: nervousness, insomnia,
high heart rate, eye disease, and anxiety.

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4. DRUGS TO TREAT HYPERTHYROIDISM
Perchlorat
Thiocyanat
Thyroid
peroxidase

I- I- I2
HO
COOH
Carbimazole H 2N
Methimazole
Propyl thiouracil

diiodotyrosin monoiodotyrosin

T3 Iodid
Thyroid
peroxidase Thyroxin
5'-deiodinase BLOOD

T4

Propyl thiouracil
Lithium
Amidaron
Thiopental
Dimercaprole
 4. DRUGS TO TREAT HYPERTHYROIDISM
O

HN H 3C N N

S N CH2CH2CH3 SH
H

Propyl thiouracil (PTU) Methimazole

O OH OH
+
TPO-I
HN N N

S N CH2CH2CH3 HS N CH2CH2CH3 I S N CH2CH2CH3

H

+
TPO-I N
H 3C N N H 3C N

SH S I

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 4. DRUGS TO TREAT HYPERTHYROIDISM

• 131I

o Offered more rapid recovery from disease, less invasive

o Based on ability of thyroid to absorb iodide
o 131I release of gamma-ray, beta-ray
o Half life 8 days

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