Kruse - Thyroid and Antithyroid Drugs DSA Flashcards
Longer half life: T4 or T3? Which is more potent?
T4 (7 days) > T3 (1 day).
T3 is more potent, but T4 is preferred therapy for hypothyroidism as thyroid replacement.
T4 and T3 absorption may be affected by myxedema with ileus, but not by mild ____?
hypothyroidism
Agents that inhibit conversion of T4 to T3 (via inhibition of 5’-deiodinase in cytoplasm) and increase reverse-T3 (inactive) levels.
Radiocontrast agents iopanoic acid and ipodanate
***Amiodarone, B-blockers, Corticosteroids
Patients experiencing ____ are administered agents that inhibit T4 to T3 conversion to reduce T3 levels?
Thyroid storm (thyrotoxic crisis)
What drugs decrease T4 absorption?
What instructions should be given to someone who is taking T4?
Cholestyramine, colestipol, cipirofloxin, PPI, ferrous sulfate, bran, soy, coffee, antacids (aluminum hydroxide, calcium carbonate)
-Instruct to take on an empty stomach
Drugs that induce hepatic CYP450s, thus increasing metabolism of T4 and T3 are ____.
Rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, imatinib, protease inhibitors
Advantages of T4 (levothyroxine) for thyroid replacement therapy
Stability, low cost, lack of allergic foreign protein, easy lab measurement of serum levels, long 1/2 life –> 1x/day dose
Agents that interfere with production of thyroid hormone
- Thioamides (block iodide organification/oxidation in the thyroid)
- Anion inhibitors (block thyroid uptake of iodide)
- Iodide (inhibit organification, decrease size/vascularity of gland)
Agents that modify tissue response to thyroid hormone
?
Thyroid gland destruction with radiation or surgery
Radioactive iodine
Name the thioamides and function.
Methimazole, Propylthiouracil (PTU)
Used for hyperthyroidism
MOA of methimazole and Propylthiouracil (PTU)
Inhibit thyroidal peroxidase-catalyzed reactions and BLOCKS IODIDE ORGANIFICATION (Inhibit TH synthesis by blocking oxidation of iodide in the thyroid gland.)
Two pregnant woman have hyperthyroidism and need agents that interfere with production of thyroid hormone. One is in her 1st trimester, one is in her 2nd/3rd trimester. What drug is given to each?
1st trimester, give PTU
2nd/3rd trimester, give methimazole
Methimazole and Propylthiouracil (PTU) - half lives and dosing.
Methimazole - half life = 6hrs; 1x/day dose
Propylthiouracil (PTU) - half life = 1.5 hours; 3-4x/day dose
How does PTU MOA differ from methimazole?
PTU blocks peripheral conversion of T4 to T3, allowing for a significantly greater fall in T3 concentration.
Most common adverse effects of methimazole and propylthiouracil (PTU).
Maculopapular pruritic rash with possible fever, nausea, GI distress
Adverse effect that is more common in PTU than methimazole?
Hepatitis
Adverse effect that’s more common in methimazole than PTU?
Cholestatic jaundice
Most serious adverse effect of methimazole and propylthiouracil (PTU).
Agranulocytosis (
Treatment for agranulocytosis induced by PTU or methimazole.
Discontinue drug and give colony-stimulating factor (pegfilgrastim or filgrastim).
What population (taking thioamide) has especially increased risk for agranulocytosis?
Especially in older patients receiving high dose methimazole
MOA of anion inhibitors (perchlorate, pertechnetate, thiocynate)
Block thyroid uptake of iodide by competitive inhibition of iodidie transport.
MOA of iodides.
Inhibit organification and hormones release, decreases size and vascularity of the hyperplastic thyroid gland.
In what three clinical settings would iodide be of use for a person with hyperthyroidism?
- Thyroid storm
- Pre-operative reduction of hyperplastic thyroid gland
- Block thyroidal uptake of radioactive isotopes of iodine in radiation emergency or exposure to radioactive iodine.
Mother did not stop taking iodide for her hyperthyroidism and it crossed the placenta. What would the fetus present with?
Fetal goiter
A person presents with an acneiform rash, swollen salivary glands, mucous membrane ulcerations, conjuctivitis, and metallic taste - what are they on?
Iodide for hyperthyroidism
What is the MOA of radioactive iodine?
It is rapidly absorbed and concentrated by the thyroid and incorporated into the follicles where the B-radiation destroys thyroid parenchyma.
Evidence of radioactive iodine B-radiation destroying thyroid parenchyma.
epithelial swelling and necrosis, follicular disruption, edema, leukocyte infiltration
Advantages of radioactive iodine treatment.
Ease of administration, effectiveness, low expense, absence of pain (no surgery).
Administration of of radioactive iodine treatment is contraindicated in what type of people?
pregnant women or those breastfeeding
What types of B-blockers are effective in management of thyrotoxicosis?
Those without sympathomimetic activity - metoprolol, PROPANOLOL, atenolol
What is the result of B-blocker use?
Improves symptoms of hyperthyroid but does not typically alter thyroid levels.
DOC for hypothyroidism - both for (1) replacement therapy and (2) drug-induced hypothyroid that is not alleviated stoppage of offending agent.
Levothyroxine (T4)
A person presents with progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death. What is this and what do you treat with?
Myxedema coma (end state of untreated hypothyroidism), treat with IV Levothyroxine (large loading dose, then smaller dosing).
Treatment of myxedema coma with T4 for someone with what ___ concomitant condition must be taken into account.
Coronary artery disease - T4 can provoke arrhythmia, angina, and acute MI
A woman wants to conceive, but cannot. What could be the cause and what is cruicial to make sure is administered once she becomes pregnant?
If hypothyroid, women are typically infertile until normal thyroid levels restored.
Maternal T4 crucial for fetal brain development.
Potential treatments for Grave’s Disease (hyperthyroid)
- Antithyroid therapy - TxOC in young pts with small glands and mild dz; methimazole preferred over PTU)
- Thyroidectomy - TxOC for pts with large glands or multinodular goiter)
- Radioactive iodine - TxOC for most people over 21
- Adjunct tx - B-blockers to control tachycardia, HTN, afib.
TxOC in young pts with Graves with small glands and mild dz
Antithyroid therapy
TxOC for pts with large glands or multinodular goiter.
Thyroidectomy
*80-90% will require replacement therapy
TxOC for most people over 21, esp those with underlying heart disaese, severe thyrotoxicosis, or elderly.
Radioactive iodine
*80% will require replacement therapy
A person is taking antithyroid therapy, but needs adjunct to control tachycardia and B-blockers are CI. What drug can be used?
diltiazem (Ca-channel blocker)
Tx regimen for thyrotoxicosis
- B-blocker for arrhythmia
- Potassium iodide - prevent TH release from gland
- IV hydrocortisone - protect from shock and decraese T4 to T3 converstion in peripheral tissues/blood
- Potentially plasmapharesis or peritoneal dialysis to lower T4 levels.
