Thyroid and Antithyroid drugs Flashcards
What is enterohepatic recycling?
T4 and T3 can be conjugated in the liver and intestine
How does TSH work?
It increases blood flow to thyroid
Increases uptake of iodine into thyroid
Increases iodination of tyrosines on thyroglobulin
Increases formation of thyroglobulin-associated T3 and T4
Increases release of stored T3 and T4
What does peroxidase do?
It is important for the formation of T3 and T4:
It catalyses the formation of monoiodotyrosine and diiodotyrosine and then triiodotyrosine.
It also couples monoiodotyrosines with diiodotyrosines to form triiodotyrosine (T3)
Its action is to pull an electron off iodine which makes it reactive.
How is T3 and T4 released?
Thyroglobulin holds T3 and T4 which it cleaves and then releases on hydrolysis.
How do thyroid hormones carry out their functions?
T4 is converted into T3 in the liver and other cells.
T3 is a ligand for thyroid hormone receptor which is a nuclear receptor (TR) and Retinoid-X-Receptor (RXR) together they form TRE (Thyroid Response Element) this results in increased or decreased gene expression
What are the effects of thyroid hormones?
Growth and maturation
Increased metabolic rate (increased uptake of AA and glucose, increase production of ATP)
Adrenergic facilitation.
What conditions most commonly cause hypothyroidism?
Autoimmune thyroid disease (Hashimoto’s)
Iodine deficiency
Surgical removal or radio-iodine treatment
Drug-induced (Lithium, antithyroid drugs, amiodarone)
What conditions most commonly cause hyperthyroidism?
Grave’s disease
Thyroid adenoma
Thyroid hypertrophy (sufficiency after deficiency) (amiodarone)
Over-production of TSH (rare)
How are T4 and T3 given as a drug?
They are available orally and T3 is also available as as an IV formulation for rapid treatment of life-threatening hypothyroidism.
What are the adverse effects of using oral/IV T3?
Sinus tachycardia and other arrhythmias
Angina
Restlessness
Tremor
What are the treatment strategies used to treat hyperthyroidism?
Remove gland and replace T4
Irradiate gland and replace T4
Inhibit thyroperoxidase
Prevent peripheral deiodination of T4
Interfere with sympathetic NS facilitating action of T3 and T4
What radiation is used for thyroid gland irradiation?
Alpha and beta-emitter which is taken orally as an iodine salt (131iodide) and beta emission leads to death of thyroid tissue. This drug has a half life of 8 days and patient ultimately becomes hypothyroid and then T4 replacement is needed.
How do thiourylenes work?
They inhibit thyroperoxidase activity.
What are some examples of thiourylenes?
Carbimazole and methimazole
Propylthiouracil (also inhibits peripheral deiodination of T4)
How are thiourylenes dosed?
They have a short half life so they are dosed 2 - 4 times daily.
They have a slow onset of action (due to stored follicle contents) meaning 3 - 4 weeks before action take place.
