Thyroid and Antithyroid drug Flashcards
What is the role of thyroid peroxidase (TPO)?
- oxidation and organification of iodide
- couple of MIT and DIT
[DIT+DIT=T4]
[DIT+MIT=T3]
What drugs may lead to primary hypothyroidism?
Lithium and amiodarone
What is cretinism?
Lack of dietary iodine, defect in T4 synthesis or thyroid development failure leading to mental retardation, short stature, protruding umbilicus and tongue, pot belly, pale and puffy face.
**mental retardation is preventable with screening and treatment of pts within 1-2 weeks of life
What thyroid preparations are given to pts with hypothyroidism?
Levothyroxin (T4) and Liothyronine (T3)
These drugs stimulate nuclear receptors resulting in gene expression with RNA formulation and protein synthesis.
Uses… hypothyroidism, myxedema, off-label weight loss supplement, Cretinism
T4 is converted to T3 at the target cells, liver and kidneys as it is much more potent.
Enzyme induction (ex from rifampin, phenobarbital, phenytoin) can increase the metabolism of thyroid hormones (T3 and T4).
AE - symptoms and signs of thyroid excess
Causes of hyperthyroidism?
Graves disease Toxic multinodular goiter Toxic adenoma Molar pregnancy Postpartum thyrotoxicosis Post-viral thyroiditis
Drugs used in hyperthyroidism?
Thioamides - propylthiouracil, methimazole
Iodine and iodide salts - lugol solution and potassium iodide
131I
B-blockers - propranolol, esmolol
Diatrizoate, glucocorticoid
Thioamides?
Propylthiouracil (PTU) and Methimazole
MOA - inhibits thyroid peroxidase (TPO) reaction, iodine organification and peripheral conversion of T4 to T3
- *PTU - inhibits both thyroid peroxidase and 5’-deiodinase
- *Methimazole - inhibits thyroid peroxidase only
Uses… Hyperthyroidism
- PTU is reserved for pts who are intolerant to methimazole
- PTU is referred in THYROID STORM due to ability to inhibit conversion of T4 to T3
- PTU used in 1st trimester b/c Methimazole may cause rare teratogenisity
Oral admin that takes 2-3 weeks for full effect. PTU (3 times a day), Methimazole (once a day). Both drugs may cause placental barrier, but PTU is safer to use.
AE - nausea, gastrointestinal disturbances, rash, agranulocytosis, hepatitis, HYPOTHYROIDISM
Iodides?
Lugol’s solution and Potassium iodide
MOA - large doses of iodide inhibit thyroid hormone synthesis (decrease organification and release) via brief TPO inhibition. There is no long term-use b/c thyroid “escapes” from effects after 10-14 days [“Wolff-Chaikoff effect”]
Lugol’s solution - mixture of iodine and potassium iodide
Potassium iodide - saturation solution
Used prior to surgical thyroidectomy to reduce size, fragility and vascularity of thyroid gland. These are used in conjunction with PTU and B-blockers in thyrotoxic crises.
Oral admin -takes 2-7 days for onset of activity
AE - Wolkff-Chaikoff effect or Jod-Basedow phenomenon (hyperthyroidism at the onset of iodine admin?), anaphylactic reaction leading to angioedema, brassy taste, burning of teeth and gums, enlargement of parotid and maxillary glands (with chronic iodide intoxication)
131 I (radioactive iodine)?
Radioactive iodine is taken up and sequestered by thyroid gland. The intracellular radioactive iodine damages the tissue through emission of toxic-B-rays. There is no effect on other tissues.
Uses - hyperthyroidism and Graves disease that are refractory to other antithyroid drugs
AE - sore throat, hypothyroidism development
*do not use in pregnant women or nursing mothers
Oral admin
Non-selective B-blockers used in hyperthyroidism?
Propranolol, Nadolol, Esmolol
MOA - competitive block of B receptors inhibiting conversion of T4 to T3
Uses… thyroid storm, thyrotoxicosis, tremor, stage fright, migraine, angina, arrhythmias, HTN
Oral and IV, 4-6 hrs until onset of duration, enters CNS
AE - B blockade, bronchospasm, AV block, heart failure, CNS sedation, lethargy, sleep disturbances
Esmolol - short acting
With pts with asthma, can be given calcium channels instead (diltiazem and verapamil) as alternatives.
Tx of thyroid storm?
B-adrenergic blockers to manage CVS problems such as tachycardia and HTN.
PTU, IV sodium iodine, glucocorticoids = inhibit peripheral conversion of T4 to T3.
Oral Diatrizoate and IV iohexol?
iodinated radiocontrat media that suppress the conversion of T4 to T3 (5-deiodinase) in the peripheral tissue, kidney and liver. It is useful in rapidly reducing the T3 concentration in thyrotoxicosis.
Perchlorate, thiocyanate, pertechnetate?
Rarely used antithyroid drugs that inhibit iodide concentration in the gland by blocking the transportation of iodine in to the thyroid gland.
Possible development of aplastic anemia.
Amiodarone?
Class III anti-arrhythmic that blocks K+ channels.
Structurally similar to thyroxin therefore can lead to hyperthyroidism followed by autoimmune mediated inflammation of thyroid gland and ultimately hypothyroidism that can be treated with levothyroxine.
Drugs that may provoke autoimmune/destructive inflammatory thyroiditis which can induce hypothyroidism?
- amiodaron
- INF-a and IL-2
- Lithium - inhibits release of hormones and thyroid enlarge (hypothyroidism)
- imatinib, sunitnib (TKRI-tyrosine kinase receptor decrease)
- aminoglutethimide, sulfonylurea
