Anti-thyroid Drugs

Anti-thyroid drugs are most often

used to treat an overactive thyroid
(hyperthyroidism) caused by Graves'
disease (Goiter). These drugs block
the formation of thyroid hormone by
the thyroid gland.

Classification of Anti-thyroid drugs

Thioamides
Iodides
Radioiodine
receptor blocking agents

THIOAMIDES
Thioamides decreases thyroid hormone
formation

Thioamides (Propylthiouracil,
methimazole and carbimazole)
prevents formation of thyroid
hormone from iodide and tyrosine.

THIOAMIDES
Mechanism of action:
These agents are actively concentrated by the thyroid
gland against a concentration gradient.
Their primary effect is to inhibit thyroid hormone
synthesis by interfering with thyroperoxidase (TPO)
mediated iodination of tyrosine residues in thyroglobulin.
Partly block the coupling of two iodinated tyrosines (DIT
and MIT) to form thyroxine (T4 ) or triiodothyronine (T3 ).

Induce the formation of goiter.

THIOAMIDES
Thioamide (rarely, thionamide) are the most important
class of antithyroid compounds in clinical practice used
in nondestructive therapy of hyperthyroidism.
These agents are potent inhibitors of TPO, which is
responsible for the iodination of tyrosine residues of
thyroglobulin and the coupling of iodotyrosine residues
to form iodothyronines.
The most clinically useful thioamides are thioureylenes
(=N-CS-N=), which are five- or six- membered
structures.

 The most clinically useful thioamides

are thioureylenes (=N-CS-N=), which
are five- or six- membered
structures. Six membered
thioamides are:

Six membered thioamide:

Propylthiouracil

6-Propyl-2-thiouracil

Brand name: Rhea

Propylthiouracil
Manufacturer: Philusa

Used to manage
hyperthyroidism which is due
to an overactive thyroid gland
(Grave's disease).

Six membered thioamide:

The ability of PTU to inhibit the
enzyme 5-D-I (thyroxine 5'deiodinase)( i.e., the peripheral
deiodination of T4 to T3) in addition
to its intrathyroidal inhibition of
thyroid hormone formation has made
PTU the drug of choice in the
emergency treatment of thyroid
storm.

Five membered thioamides:

Methimazole

Brand name Tapazole:

Manufacturer: A.
Menarini

1-Methylimidazole-2-thiol For the treatment of hyperthyroidism,

goiter, Graves disease and psoriasis.

Five membered thioamides:

Carbimazole

Ethyl 3-methyl-2thioimidazoline-1carboxylate

Brand name: Neomerdin

Manufacturer: MedChoice Pharma

For the treatment of

hyperthyroidism and thyrotoxicosis.
It is also used to prepare patients
for thyroidectomy

Structure-activity relationships
The C2 thioketo/ thioenol group and an
unsubstituted N1 position are essential for
activity of six membered thioamides.
The enolic hydroxyl group at C4 in PTU and the
presence of alkyl group at C5 and C6 enhance the
inhibitory potency.

6-Propyl-2-thiouracil

Structure-activity relationships

Methimazole has more TPO inhibitory activity and is longer

-acting than PTU but , in contrast to PTU, is not able to
inhibit the peripheral deiodination of T4, presumably
because of the presence of the methyl group at N1 position.

Structure-activity relationships
Efforts to improve the taste and
decrease the rate of release of
methimazole led to the development
of carbimazole.
Carbimazole, the pro-drug derivative
of methimazole, gives rise to
methimazole in vivo and is used in
the same dosage.

IODIDES
Iodides in High Concentrations Decrease
Thyroid Activity and Thyroid Gland Size.
When iodides are present in the blood in high
concentration (100 times the normal plasma
level: 0.6 to 0.8 g/lit), most activities of the
thyroid gland are decreased.
Reduce the rate of iodide trapping
Decrease its blood supply
It also lowers the elevated BMR.
Net effect is the reduction of size of thyroid gland

IODIDES
It also has been suggested that excess iodide might
change the conformation of thyroglobulin, making
the protein less susceptible to thyroidal proteolysis.
Iodide, as Lugol's solution (Strong Iodine Solution
USP) or as saturated potassium iodide solution, is
administered for approximately 2 weeks to ensure
decreased vascularity and firming of the gland.
Lugols solution contains 5% iodine (5 grams in 100
mL) and 10% potassium iodide (10 grams in 100
mL).

RADIOACTIVE IODIDE
Definitive treatment: given primarily to destroy the hyper
functioning thyroid tissue.
Available as Sodium iodide I 131 (Na131I)
Radioiodine is an oral medication and given as single dose.
Patients taking radioiodine therapy, few required more than
one dose.
Usual dose: 100 to 200 Ci per gram of weight of thyroid
gland.

RADIOACTIVE IODIDE
Radioiodine is taken by the follicular cell in the
same way as iodine and beta emission of
radioiodine causes necrosis and decrease the
activity of thyroid tissue.
The cell necrosis induced by radioiodine occurs
gradually.
May elapse hyperthyroidism (after 6-18 weeks or
later of the treatment) before a hypothyroid or
euthyroid state is achieved.

RADIOACTIVE IODIDE
Pregnancy: Sodium iodide I 131 has been shown to cause harm to a
developing fetus. Use in pregnant women should be avoided.
Nursing mother: Iodine is excreted in breast milk. Therefore,
formula feedings for infants are strongly recommended for nursing
women requiring sodium iodide I 131 treatment.
The side effects commonly seen with sodium iodide I 131 treatment
are mild with the smaller doses given for hyperthyroidism but may
be more severe with the larger doses given for thyroid cancer.
Sodium iodide I 131 may cause suppression of the bone marrow,
resulting in anemia, and reductions in white blood cells and
platelets.
Increased risk of death from cardiovascular