"Pharmacology Thyroid Ying Huang" Flashcards
What enzymes convert T4 to T3?
D1 and D2 deiodinases
D1 - liver and kidney
D2 - CNS, pituitary gland, thyroid, heart, brown adipose tissue, skeletal muscle
What is D3?
D3 deiodinase - predominantly in brain and skin and placenta
Inactivates T3 to T2
What is the cause of congenital hypothyroidism?
Mutations in the sodium-iodide symporter gene affecting iodide transport
What causes Hashimoto’s thyroiditis?
Autoantibodies attack the sodium-iodide symporter and cause hypothyroidism
Hyperthyroidism has what levels of TSH and T4?
Hyperthyroidism:
Low TSH
High T4
Primary hypothyroidism has what levels of TSH and T4?
Primary hypothyroidism:
High TSH
Low T4
Secondary hypothyroidism has what levels of TSH and T4?
Secondary hypothyroidism:
Low TSH
Low T4
What are common causes of hypothyroidism?
Hashimoto's Iodine deficiency Thyroid ablation Secondary hypothyroidism (pituitary disorder, hypothalamic disorder such as adenoma or radiotherapy) Myxedema Cretinism
Class: Levothyroxine
Synthetic thyroid hormone (T4)
MOA: Levothyroxine
Converted to T3 in liver; T3 binds to TR complex to influence gene expression
Half life of 6-7 days
Uses: Levothyroxine
Drug of choice for hypothyroidism (longer half-life than T3)
Side effects: Levothyroxine
Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss
Class: Liothyronine
Synthetic thyroid hormone (T3)
MOA: Liothyronine
T3 binds to TR complex in nucleus to influence gene expression
Half life of 1 day
Uses: Liothyronine
Acute management of hypothyroidism (rapid effect); myxedema coma (IV formulation)
Side effects: Liothyronine
Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss
Class: Liotrix
Synthetic thyroid hormone (T4 & T3)
MOA: Liotrix
Converted to T3 in liver; T3 binds toTR complex to influence gene expression
Uses: Liotrix
Thyroid hormone replacement therapy (4:1 mix of T4:T3; not used much)
Side effects: Liotrix
Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss
Levothyroxine is not indicated in patients with:
Chronic Fatigue Syndrome bc they have difficulty converting T4 to T3
Use Liothyronine in these patients
What is the drug of choice for acute hypothyroidism, such as myxedema coma?
IV formulation of Liothyronine
What causes Grave’s disease?
Thyroid-stimulating antibodies which bind to and activate the thyrotropin receptor on thyroid cells
The second most common cause of hyperthyroidism is nodular goiter (older age group). Other causes include thyroiditis or thyroid cancer.
Why would a beta blocker such as propranolol be indicated for hyperthyroidism?
It would dampen the sympathetic effects of the hyperthyroid function
Class: Propylthiouracil
Thioamide (thyroid peroxidase inhibitors)
MOA: Propylthiouracil
Inhibit organification of iodide and coupling of iodotyrosine; also reduces peripheral deiodination of T4 to T3 by D1
Uses: Propylthiouracil
Hyperthyroidism; thyrotoxicosis (high dose); drug of choice for hyperthyroidism during pregnancy
Side effects: Propylthiouracil
Rare side effects: hepatitis, agranulocytosis (higher than methimazole), lupus-like syndrome
Class: Methimazole
Thioamide (thyroid peroxidase inhibitors)
MOA: Methimazole
Inhibit organification of iodide and coupling of iodotyrosine; active metabolite of carbimazole; less effect on T4 to T3 conversion
Uses: Methimazole
Hyperthyroidism; thyrotoxicosis (high dose)
Side effects: Methimazole
Rare side effects: hepatitis, agranulocytosis (less than propylthiouracil), lupus-like syndrome
Class: Carbimazole
Thioamide (thyroid peroxidase inhibitors)
MOA: Carbimazole
Prodrug converted to methimazole; Inhibits organification of iodide and coupling of iodotyrosine; less effect on T4 to T3 conversion
Uses: Carbimazole
Hyperthyroidism; thyrotoxicosis (high dose)
Side effects: Carbimazole
Rare side effects: hepatitis, agranulocytosis, lupus-like syndrome
In thyrotoxicosis, what route of administration may be necessary?
Rectal
Which antithyroid drug has a higher risk of agranulocytosis, propylthiouracil or methimazole?
Propylthiouracil
Propylthiouracil is the preferred antithyroid drug in what patient population?
Pregnant and breast-feeding patients
Patients taking an anti-thyroid who develop agranulocytosis are then candidates for what therapies?
Radioactive iodine or surgery
Class: Radioactive Iodine
Radioactive isotope
MOA: Radioactive Iodine
Radioactive agent that emits beta particles and gamma rays that destroy thyroid cells
Uses: Radioactive Iodine
Treatment of choice for hyperthyroidism after antithyroid drug therapy; ablation after cancer
Side effects: Radioactive Iodine
Transient or permanent hypothyroidism; increases cancer risk
Radioactive iodine is contraindicated in what patient population?
Pregnant and breastfeeding patients
