Thyroid and Anti-Thyroid Drugs Flashcards
What are the 4 thyroid drugs?
- Levothyroxine [T4]
- Liothyroxine [T3]
- Liotrix [a 4:1 ratio of T4:T3]
- Thyroid desiccated
What are the 4 anti-thyroid agents?
- Radioactive iodine (131I) sodium
- Methimazole
- Potassium iodide
- Propylthiouracil [PTU]
Which iodide transport enzyme controls the flow of iodide across the apical membrane of the thyroid follicular cell?
Pendrin
Where is oral T4 best absorbed within the GI tract?
Duodenum and ileum
T4 and T3 absorption may be affected by what underlying condition?
Myxedema w/ ileus but NOT by mild hypothyroidism
How does the half-life and clearance of T4 and T3 change in a hyperthyroid vs. hypothyroid state?
- Hyperthyroid = T4 and T3 clearance is ↑ and half-life ↓
- Hypothyroid = T4 and T3 clearance is ↓ and half-life ↑
Which 6 agents inhibit 5’-deiodinase, blocking T4 to T3 conversion and increasing reverse T3 levels, and may be given in pt’s experiencing thyroid storm?
- Radiocontrast agents: iopanoic acid and ipodate
- Amiodarone
- β-blockers
- Corticosteroids
- PTU
- Flavanoids
List 9 drugs/agents that decrease T4 absorption?
- Antacids (aluminum hydroxide, calcium carbonate)
- Ferrous sulfate
- Cholestyramine
- Colestipol
- Ciprofloxacin
- PPI’s
- Bran, Soy, and Coffee
List 7 drugs which induce hepatic CYP450s and increase the metabolism of T4 and T3?
- Rifampin
- Rifabutin
- Phenobarbital
- Phenytoin
- Protease inhibitors
- Carbamazepine
- Imatinib
List 5 agents that are responsible for the induction of autoimmune thyroid diseas w/ hypo- or hyperthyroidism.
- Interferon-α
- Interferon-β
- Interleukin-2
- Lithium
- Amiodarone
How long after administering thyroid hormone does it take to see the effects and why?
Lag time of hours or days due effects at the level of gene transcription
After T3 enters the nucleus and binds the thyroid receptor (TR) what occurs?
- Corepressor is released and coactivator binds to the TR
- Homodimer separates, and TR binds to RXR (retinoid X receptor)
- Gene transcription ensues
Even though T3 is 3-4x more potent than T4, why is it not recommended for routine replacement therapy?
- Short 1/2 life (requires multiple daily doses)
- Higher cost
- Difficulty w/ monitoring its adequacy of replacement
What are preparations of T3 best used for clinically?
Short-term suppression of TSH
What is the absorption, bioavailability, metabolism, half-life, and dosing like for the anti-thyroid drug, PTU?
- Rapidly absorbed, peak serum after 1 hour
- 50-80% bioavailability (incomplete absorption and/or large first-pass effect)
- Renal excretion (virtually all metabolites in 24 hrs)
- Half-life = 1.5 hours
- 3-4 doses/day (compared to 1x/day for Methimazole)
What is the absorption, bioavailability, metabolism, half-life, and dosing like for the anti-thyroid drug, Methimazole?
- Completely absorbed
- Slower renal excretion than PTU (65% dose recovered - 48 hrs)
- Half-life = 6 hrs
- Once daily dosing
Why are the anti-thyroid drugs, PTU and Methimazole, generally not recommended in pregnancy; which drug should be given if therapy is requied?
- Can cross the placenta and become concentrated in fetal thyroid
- PTU is recommended in first trimester
- Methimazole is drug of choice in second and third trimester
What is the main MOA of both PTU and Methimazole?
- Inhibit thyroidal peroxidase-catalyzed rxns
- Blocks iodide organification
- Inhibits coupling of MIT and DIT to form T3 and T4
How does the fall in T3 concentration with PTU + iodine differ from that of Methimazole + iodine?
PTU blocks peripheral conversion of T4 –> T3; significantly greater fall in [T3] and T3:T4 ratio
What effect to PTU and Methimazole have on thyroid gland iodide uptake?
- Do NOT block thyroid gland iodide uptake
- Act to inhibit hormone synthesis, rather than release
How long must therapy with PTU or Methimazole be given before stores of T4 and T3 are depleted?
3-4 weeks of therapy
What are the most common AE’s associated with PTU or Methimazole?
- Maculopapular pruritic rash, at times accompanied by:
- Fever + nausea + GI distress
What are some of the rare AE’s associated with PTU or Methimazole; which is more specific to each?
- Urticarial rash + Vasculitis + Lupus-like rxn
- LAD
- Hypoprothrombinemia
- Acute arthralgia
- Hepatitis (more common w/ PTU)
- Cholestatic jaundice (more common w/ methimazole)
What is the most serious AE associated with PTU or Methimazole; who is most at risk and how is this condition reversed?
- Agranulocytosis (granulocyte count <500 cells/mm3)
- Risk ↑ in older pt’s and those receiving high-dose methimazole
- Reversed w/ drug discontinuation and CSF’s
What is the MOA of the monovalent anions perchlorate, pertechnetate, and thiocyanate as anti-thyroid agents?
Block thyroid gland uptake of iodide by competitively inhibiting the iodide transport mechanism
What is the MOA of the anti-thyroid agent, Potassium Iodide?
- Inhibit organification and hormone release
- ↓ the size and vascularity of hyperplastic thyroid gland
What are the 3 clinical uses of the anti-thyroid agent, Potassium Iodide?
1) Thyroid storm - thyrotoxic sx’s improve rapidly (within 2-7 days)
2) Preoperative reduction of hyperplastic thyroid
3) Block thyroidal uptake of radioactive isotopes of iodine in a radiation emergency or other exposure to radioactive iodine
Although uncommon, what are some of the AE’s which may be seen with the anti-thyroid agent, Potassium Iodide?
- Acneiform rash
- Swollen salivary glands
- Mucous membrane ulcerations
- Conjunctivitis
- Metallic taste
Who should you avoid giving the anti-thyroid agent, Potassium Iodide?
Pregnant women, since iodides can cross the placenta and cause fetal goiter
What effect does radioactive iodinde (131I) have on the thyroid?
β-ray radiation causes destruction of thyroid parenchyma, evidenced by epithelial swelling, follicular disruption, edema, and leukocyte infiltration
What is radioactive iodinde (131I) used for and what are the advantages of using it?
- For tx of thyrotoxicosis
- Advantages = ease of administration, effectiveness, low expense, and absence of pain
Which β-blockers are effective adjunctive agents in the management of thyrotoxicosis and which is most commonly used?
- Those w/o sympathomimetic activity (i.e., metoprolol, propranolol, and atenolol)
- Propranolol is most commonly used
What effect do β-blockers have on thyroid levels?
- Improve hyperthyroid sx’s, but typically do not alter levels
- High doses of propranolol have been shown to reduce T3 through blockade of peripheral conversion of T4 –> T3
Radioactive iodine 131I is contraindicated in whom?
Women who are pregnant or breast feeding
Which anti-thyroid drugs are considered safe in women who are breast feeding?
The thiomides —> PTU and Methimazole
How do adults differ from infants/children in the amount of T4 needed per body weight?
Infants/children require MORE T4 per body weight than adults
How should T4 be given and how long does it take to reach steady state levels?
- Given on empty stomach (due to interactions with foods and drugs)
- Takes 6-8 weeks to reach steady-state levels
How is hypothyroidism managed in someone with myxedema coma as far as route of administration and dosing?
- Give T4 via IV due to poor absorption in pt’s w/ myxedema coma
- Large loading dose of T4 followed by smaller IV dosing
How should a patient with myxedema and coronary artery disease be managed with T4?
Correction of myxedema with T4 must be done cautiously to avoid provoking arrhythmia, angina, or acute MI (sx’s of elevated T4)
Why is management of hypothyroidism in pt’s trying to get pregnant and those currently pregnant so important?
- Hypothyroid women are typically infertile until restoration of normal thyroid levels
- Maintenance of normal levels is crucial due to fetal brain development dependence of maternal T4
When is anti-thyroid drug therapy most useful for Grave’s disease and what are the preferred agents?
- Most useful in young pt’s w/ small glands and mild disease
- Methimazole or PTU administered until remission (12-18 mo. of tx)
- Methimazole is preferable to PTU (EXCEPT in pregnancy) due to once-daily dosing
When is a thyroidectomy the preferred tx for Grave’s disease and what % of these pt’s will require thyroid supplementation?
- Tx of choice for pt’s w/ very large glands or multinodular goiter
- 80-90% will require thyroid supplementation
When is radioactive iodine the preferred tx for Grave’s disease; what about in pt’s w/ underlying heart disease, severe toxicosis, and the elderly?
- Preferred tx for most pt’s >21 years of age
- In pt’s w/ underlying heart disease, severe thyrotoxicosis, or elderly tx w/ anti-thyroids until pt is euthyroid is preferable
- 80% will develop hypothyroidism and require replacement therapy
What are the adjunct drugs which can be added to anti-thyroid therapy in pt with Graves?
- β-blockers w/o intrinsic sympathomimetic activity may be helpful in controlling tachycardia, HTN, and atrial fibrillation
- If β-blocker is contraindicated can give the CCB, diltiazem, for management of tachycardia
Which drugs are indicated for treating thyroid storm (thyrotoxic crisis) and why is each given?
- β-blockers to control the arrhythmia
- Potassium iodide to prevent release of thyroid hormones from thyroid gland
- PTU or methimazole to block hormone synthesis
- IV hydrocortisone to protect against shock and to block conversion of T4 to T3 in peripheral tissues/blood
- Supportive therapy to control any underlying issues
In the rare situation where anti-thyroid agents are inadequate in controlling thyroid storm, what can be done?
Plasmapheresis or peritoneal dialysis may be used to lower levels of circulating T4
