Thyroid & Antithyroid Drugs

thyroglobulin

Fig 1 Fig 2

＊Thyroid follicles are the structural & functional units of the thyroid gland.
＊ Each follicle is surround mainly by simple cuboidal epithelium and is
filled with a colloid which mainly composed by thyroglobulin.
＊ Thyroid hormones are mainly synthesized in colloid while the simple
cuboidal epithelium undertaking thyroglobulin production, iodide intake &
thyroid hormones release. 1
●Synthesis of thyroid hormones
Thyroid hormones MIT: monoiodotyrosine
triiodothyronine (T3) DIT: diiodotyrosine
tetraiodothyronine (T4, thyroxine)
Materials
iodine & tyrosine
Steps thyroglobulin harmon

1. Iodide is trapped by sodium-iodide symporter

2. Iodide is oxidized by thyroidal peroxidase to iodine
3. Tyrosine in thyroglobulin is iodinated and forms MIT & DIT
4. Iodotyrosines condensation
MIT+DIT→T3; DIT+DIT→T4 2
●Regulation of thyroid function

Anterior

TRH: thyrotropin-releasing hormone

Feedback TSH: thyroid-stimulating hormone
inhibition

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●Mechanism of actions
of thyroid hormones
T3, via its nuclear
• Both T4 and T3 dissociate receptor, induces
from thyroxine-binding plasma
proteins before entering cells new proteins
generation which
• T4 is converted to T3, which
enters the nucleus and binds produce effects
to specific receptors

• BMR: basal metabolic rate

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Hypothyroidism (usually results Hyperthyroidism (associated with
from autoimmune destruction of the Graves disease, toxic adenoma,
gland; elevated TSH) and goiter; TSH levels reduced due
to feedback inhibition)

Symptoms: Symptoms:
1. Bradycardia 1. Tachycardia
2. Poor resistance to cold 2. Cardiac arrhythmias
3. Mental & physical slowing 3. Body wasting
(retardation and dwarfism in 4. Nervousness
children) 5. Tremor
6. Excess heat production

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Treatment of hypothyroidism
• Levothyroxine (L-T4)
• Given once daily (t0.5 = 1 week)
• Steady state is achieved after 6-8 weeks
Toxicity (related to elevated T4 levels):
• Nervousness, palpitations, tachycardia,
heat intolerance, and unexplained weight
loss.

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Treatment of hyperthyroidism
(thyrotoxicosis)
1. Removal of part or all of the thyroid (surgically or
using radioactive iodine 131I). Subsequent treatment
with levothyroxine might be required.
2. Inhibition of thyroid hormone synthesis (using
thioamides)
3. To treat severe hyperthyroidism (thyroid storm), beta-
blockers that lack sympathomimetic activity are used
(propranolol).
4. Blockade of hormone release (using iodides)

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 Antithyroid drugs
● Drugs

Class Representative
propylthiouracil
methylthiouracil
Thioamides
methimazole
carbimazole
Iodides KI, NaI
131I
Radioactive iodine
β-adrenoceptor blockers propranolol
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Pharmacological action
Inhibition of the synthesis of T3 & T4

Mechanism
All thioamides inhibit peroxidase-catalyzing reactions
Iodine organification First choice for
Iodotyrosines condensation thyroid crisis
Propylthiouracil also inhibit T4 converting to T3

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Clinical use
treatment of hyperthyroid
1. Mild hyperthyroid and those surgery & 131I
not permitted;
2. Operation preparation;
3. Thyroid crisis (comprehensive therapy).

Adverse reactions
1. Long-term use leads to thyroid hyperplasia;
2. Pruritic maculopapular rash is the most common
adverse reaction
3. The severe adverse reaction is agranulocytosis
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 Iodides (NaI, KI)
Pharmacological action
Inhibition of T3 & T4 release and synthesis
Decrease of size & vascularity of the hyperplastic gland

Clinical use
Ministrant treatment of hyperthyroid
1. Operation preparation;
2. Thyroid crisis.

Adverse reactions
1. Rash
2. Swollen salivary glands, mucous membrane ulcerations, and etc.
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 Radioactive iodine (131I)

131I is the only isotope for treatment of thyrotoxicosis.

Its therapeutic effect depends on emission of β rays with an
effective half-life of 5 days & a penetration range of 0.4-2 mm.
Woman in pregnancy or lactation is forbidden!

β-adrenoceptor blockers
βblockers are effective in treatment of thyrotoxicosis.
Propranolol is the most widely studied and used.

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Thank you

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