Thyroid medications Flashcards
Define:
Euthyroid, hypothyroidism, hyperthyroidism, thyroiditis, thyrotoxicosis
Euthyroid - normal levels of thyroid function
Hyperthyroidism- too much thyroid hormone function
Hypothyroidism - too little thyroid hormone function
Thyroiditis - inflammation of the thyroid gland
Thyrotoxicosis - state caused by too much thyroid hormone in the body
Function of the thyroid gland
secretes hormones that regulate human growth and development by modulating a number of metabolic and physiological processes
Levothyroxine (Thyroxine, T4) mechanism of action
Levothyroxine is a synthetic form of the natural T4 hormone, thyroxine.
Although levothyroxine is a synthetic form of T4, it serves as a source of T3 within the body by deiodination (approximately 80% of T3 is derived locally from T4 by conversion in target tissues).
Levothyroxine is generally considered the treatment of choice for hypothyroidism because it provides both T4 and T3.
When should levothyroxine be taken? Who has to take a higher dose?
Should be taken on an empty stomach
Infants need higher dose because metabolise T4 faster (slows with age)
Levothyroxine drug interactions
Aluminum-containing antacids, calcium carbonate, and proton pump inhibitors can also interfere with the absorption of thyroid hormones.
Cholestyramine can bind thyroid hormones in the intestine and block absorption.
Thyroid hormones stimulate the catabolism of vitamin K-dependent clotting factors and so can influence the action of various anticoagulants.
Black box warning for thyroid medications
None should be used for weight loss
Liothyronine (Triiodothyronine, T3) mechanism of action
Liothyronine is a synthetic form of the natural T3 hormone.
Because there is no need to metabolize liothyronine to an active drug it has a more rapid onset of action than levothyroxine.
As the active drug, liothyronine is approximately 4 times as potent as levothyroxine.
What is different about liothyronine concentrations
The half-life of liothyronine is shorter than that of levothyroxine, so liothyronine supplements are generally taken multiple times a day compared to once daily for levothyroxine.
Rapid onset together with shorter half-life means there can be wider concentration swings with liothyronine leading to more fluctuation in clinical response.
Why does liothyronine have limited use
Concentration swings tend to offset any advantages seen with liothyronine compared to levothyroxine and therefore limit its use.
Liothyronine is also more expensive than levothyroxine.
What is liotrix? Is it used?
A 4/1 mixture of T4 and T3, respectively meant to more closely mimic thyroid output)
There is no therapeutic benefit reported for liotrex compared to levothyroxine and there is an increased risk for elevated T3 concentrations when using liotrix.
Two main approaches for treating hyperthyroidism:
1) Reducing the amount of thyroid tissue capable of producing thyroid hormones
2) Reducing the amount of thyroid hormones produced from pre-existing thyroid tissue.
Why is thyroid ablation considered a good option for hyperthyroidism?
it is generally considered easier and safer to treat hypothyroidism by hormone replacement therapy that in is to treat hyperthyroidism by non-ablative approaches
What is the coarse of action for abblation by radiotherapy and for thyroid cancer
Radioactive iodide ( 131I) is a β particle emitter with a half-life of 8 days, selectively toxic for thyroid cells
What is thyroid peroxidase (TPO)
TPO is a heme-containing peroxidase that catalyzes the iodination of tyrosine residues in thyroglobulin (Tg) and the subsequent phenolic coupling of iodinated tyrosine residues to give Tg-bound precursors of thyroxine (T4) and tri-iodothyronine (T3)
What do thioamides do?
Thioamide drugs inhibit thyroid peroxidase (TPO) blocking the iodination of tyrosine residues in thyroglobulin and the phenolic coupling of iodinated tyrosine residues to form precursors of T4 and T3.
What are some commonly used thioamides
propylthiouracil (PTU), methimazole, carbimazole
Mechanism for thioamides
bind to the active site of the TPO enzyme and function as an alternative substrate for iodination, thereby reducing the iodination of tyrosine residues in Tg
Onset of action for thioamides
Therapeutic effect requires time to deplete stores of iodinated Tg and pre-existing T3/T4. Depletion of storage pools can take 4-6 weeks.
Which thioamide should be used during pregnancy?
Carbimazole and methimazole cross the placental membrane more effectively than propylthiouracil, making propylthiouracil the drug of choice during pregnancy.
Major adverse reaction for propylthiouracil
high level of hepatotoxicity including death associated with propylthiouracil use, particularly in children
Mechanism of Monovalent anion transport inhibitors
Drugs in this class target iodide uptake into the thyroid.
These drugs include: thiocyanate (SCN -), perchlorate (ClO4 -), and pertechnetate (TcO4 -).
What is the Wolff-Chaikoff effect?
Is the basis for using pharmacological doses of iodine to treat certain forms of hyperthyroidism.
plasma inorganic iodine acts as a homeostatic regulator in the formation of the thyroid hormone. This regulator probably serves to prevent the formation of excessive amounts of hormone by the gland when the body is suddenly flooded with iodine.
mechanisms underlying the Wolff-Chaikoff effect
The primary mechanism by which pharmacological doses of iodine reduce thyroid hormone levels appears to be through the inhibition of the proteolytic release of T3 and T4 from thyroglobulin in lysosomes.
EVentually, Iodine receptors are down-regulated so not a long-term solution for hyperthyroidism
What is the Jod-Basedow phenomenon?
In persons lacking the normal autoregulatory response to iodine (elderly, autonomous thyroid nodules, low iodine regions of the world without iodine supplementation) pharmacological doses of iodine can induce hyperthyroidism.
Iodine-induced thyrotoxicosis can be observed in susceptible individuals receiving iodine contrast agents for radiographic imaging and in susceptible indivduals taking iodine-rich drugs.
Why are B blockers used in hyperthyroidism
Antagonists of β -adrenergic receptors (beta-blockers) can be used to relieve symptoms of hyperthyroidism including tachycardia, anxiety, and heat intolerance.
The basis for the effect of beta blockers in symptomatic relief of hyperthyroidism is that thyroid hormones are known to increase the number of β -adrenergic receptors in a number of tissues making these tissues more sensitive to sympathetic stimulation.
Receptor antagonists would therefore reduce receptor activation by epinephrine and norepinephrine providing relief for symptoms caused by enhanced sympathetic sensitivity.
