Lecture 23 - Chemistry of Thyroid Treatments Flashcards
Two thyroid hormones?
Thyroxine (T4)
Triiodothyronine (T3)
How are thyroid hormones transported in the blood?
bound to proteins
How active are thyroid proteins?
active in unbound form and have function in almost all cells
What does the thyroid gland convert tyrosine to?
monoiodotyrosine (MIT) and diiodotyrosine (DIT)
What do TSH and TRH act as?
a system to regulate production of T3 and T4
What converts T4 to T3
5’- deionase enzyme
MIT and DIT give?
T3
DIT and DIT give?
T4
How do disease states alter the thyroid system?
by changing the chemistry
Hypothyroidism?
underproduction of the thyroid hormones
Hypothyroidism causes?
insufficient iodine in the diet, Hashimoto’s thyroiditis, inflammation to the thyroid gland (lymphocytic thyroiditis)
Hyperthyroidism?
overproduction of the thyroid hormones
Hyperthyroidism causes?
overactive thyroid gland producing excess thyroid hormones
Hypothyroidism treatment?
levothyroxine and liothyronine
Levothyroxine physiochemistry?
log P = 7.4
pKa = 10, 9, 4
Liothyronine physiochemistry?
log P = 6
pKa = 10, 9, 4
What allows conversion of levothyroxine and liothyronine to salts?
The carboxylic acid functional group
How are levothyroxine and liothyronine given?
orally to replace deficient thyroid hormones
can be given by IM injection if required
How do anti thyroid drugs work?
by preventing the synthesis of thyroid hormones
Carbimazole physiochemistry?
log P = 0.3
What is carbimazole?
a prodrug
converted to methimazole
Methimazole physiochemistry?
log P = -0.3
What does carbimazole lose to become methimazole?
the methyl group and the ester group, this decreases the log P
What does active methimazole do?
inhibits thyroid peroxidases which convert tyrosine to MIT and DIT
What does no MIT and DIT mean?
no T3 and T4
Propythiouracil physiochemistry?
Log P = 0.4
How does propythiouracil work?
inhibits thyroid peroxidases which convert tyrosine to MIT and DIT
What else does propythiouracil do?
inhibits 5’-deionase enzymes helping to stop T3 biosynthesis
How are carbimazole and propythiouracil administered?
as tablets
