Treatment of Hyperthyroidism

Amit Nayak
 Hyperthyroidism
• The increased oxygen demand leads to an
increased heart rate and increased cardiac
output and, thereby, places strain on the heart
• Exaggerated catabolic processes lead to
decreased serum cholesterol and to poor
glucose tolerance and glucosuria
• excessive calorigenic effect produced by
catabolic processes causes anorexia and poor
thermoregulation
 Antithyroid Drugs for the Treatment of
Hyperthyroidism
• Iodide
• Methimazole, Propylthiouracil, and Related
Compounds
 Iodide
• Inhibition of the release of thyroid hormone by iodide is the basis for its
use in hyperthyroidism.
• Iodide decreases the vascularity of the enlarged thyroid gland and also
lowers the elevated BMR.
• It also has been suggested that excess iodide might change the
conformation of thyroglobulin, making the protein less susceptible to
thyroidal proteolysis.
• the role of iodide in hyperthyroidism has been relegated to that of
preparation for thyroid surgery.
• 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.
• Iodism, a side effect of iodine administration, is apparently an allergic react
ion characterized by dermatological and common cold- like symptoms
Methimazole, Propylthiouracil, and Related
Compound
• Thionamides are the most important class of
antithyroid compounds in clinicalpract ice used
in nondestructive therapy of hyperthyroidism
• potent inhibitors of TPO, which is responsible for
the iodination of tyrosine residues of
thyroglobulin and the coupling of iodotyrosine
residues to form iodothyronines
• no effect on the iodide pump or on thyroid
hormone release
Contd….
Chemically, the grouping R-CS-N- as
been referred to as thioamide,
thionamide, thiocarbamide, or if R is
N, as it is in thiouracil, PTU, and MMI,
it is called a thioureylene. This
structure may exist in either the
thioketo or thioenol tautomer ic
forms.
 SAR
• The study of 6-alkylthiouracil showed maximal
antithyroid activity with 6-propylthiouracil . 6-
Methylthiouracil has less than one- tenth the
activity of PTU.
• The C2 thioketo/ thioenol group and an
unsubstituted N1 position are essential for activity
• The enolic hydroxyl group at C4 in PTU and the
presence of alkyl group at C5 and C6 enhance the
inhibitory potency
 SAR Contd…
• 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.
The suggested maintenance dosages listed in USP DI are 50
to 800 mg daily for PTU and 5 to 30 mg daily for MMI
• Efforts to improve the taste and decrease the rate of release
of MMI led to the development of 1-carbethoxy-3-
methylthioimidazole (carbimazole) . Carbimazole, the pro-
drug derivative of methimazole, gives rise to methimazole in
vivo and is used in the same dosage
 Side-Effects
• The side effects of thioamides include
diarrhea, vomiting, jaundice, skin rashes, and
at times, sudden onset of agranulocytosis.
There does not appear to be a great difference
in toxicity among the compounds currently in
use