Thyroid Pharmacology Flashcards
What are the relative half lives and potency of thyroid hormone?
T4: half life is 7 days
T3: half life is only 1 day but it is 4x more potent
Are there greater levels of free T4 or free T3? About how much is there?
There is about 10x more free T3. Unbound T3 constitutes .4% of the total thyroid hormone
What are the three classes of thyroid hormone preparations?
Levothyroxine: LT4
Liothyronine: LT3
T4/T3 Mixes: just don’t use them
Why is hypothyroid treated with T4? (2)
Longer half life and peripheral conversion via deiodination
When is T3 use indicated? (2)
Myxedema coma
Withdrawal for thyroid cancer radioactive iodine treatment
When do you see side effects from thyroid treatment?
Only from inappropriate dosing
What are some dosing considerations when starting therapy?
Starting dose depends on age, degree of thyroid failure of patient
How often is TSH levels monitored?
What is the target range? Does this change for people of different ages?
Check TSH about every 6 weeks
Target TSH normal range (.5-5) with target usually below 2.5. The target is usually higher in older people
What are reasons for TSH levels being higher than expected? (6)
Noncompliance Drugs that decrease LT4 absorption Conditions that decrease LT4 absorption: SI disease Drugs that increase LT4 metabolism Increased TBG Progression of thyroid disease
Name some drugs that increase LT4 metabolism.
Name some factors that increase TBG
Drugs: phenytoin, rifampin, phenobarbital, carbamazepine
Increased TBG seen during pregnancy, estrogens, hepatitis
Why would TSH on therapy be lower than expected? (5)
Dopamine High dose glucocorticoids Decreased TBG Self-administration of excess LT4 Reactivation of Grave's disease or development of autonomous nodules
What are some factors that decrease TBG? (4)
Androgens
Nephrotic syndrome
Chronic liver disease
Severe systemic illness
What are drugs that cause hypothyroidism? (5)
Primary: amiodarone, lithium, INFa, aminoglutethimide
Secondary bexarotene
For what conditions should you involve a endocrinologist to monitor TSH levels? (2)
Pregnancy
Thyroid cancer
What do you do to treat myxedema coma? Why?
First IV hydrocortisone to fix adrenal
Give LT4/LT3 IV–decreased metabolism for most medications
What is the mechanism of antithyroid drugs?
interfere with two steps of thyroid hormone synthesis via TPO
- Intrathyroidal iodine utilization
- Iodotyrosine coupling
When do you use antithyroid drugs?
Graves disease
To cool patient down prior to RAI or surgery
What are two antithyroid drug? Which is preferred? Why? (3)
PTU and Methimazole.
Mithimazole has longer half life– longer duration of action.
Mithimazole is not protein bound.
PTU decreases T4-T3 conversion
When do you use methimazole? When do you use PTU? (3)
Use methimazole in all Grave’s disease patients except:
First trimester of pregnancy
Thyroid storm
AE to methimazole
What are the main side effects of antithyroid drugs? (6)
Agranulocytosis, severe hepatitis (just PTU), cholestasis (MMI), vasculitis, polyarthritis, skin rxns
What is the greatest concern with antithyroid drugs?
How is it monitored?
Agranulocytosis, which occurs in .1-.5% patients at any time.
They should stop antithyroid drug and check WBC if fever or sore throat.
Which drugs inhibit T4-T3 conversion? (3)
PTU
Glucocorticoids
Propanolol
Which other drugs can you use in hyperthyroidism? (3)
Beta-blockers
NSAIDs in subacute thyroiditis
Iodine/glucocorticoids in severe thyrotoxicosis
Which drugs do you use in treatment of Thyroid Storm? (4)
PTU
Propanolol or esmolol
Hydrocortisone
Potassium iodide drops
How is iodide uptake mediated? How does it correspond to dietary supply?
Iodide uptake is mediated by the Na/I symporter (NIS).
Low iodide increases NIS; high iodide decreases NIS
Where is NIS expressed?
High levels in thyroid
Low levels in salivary glands, lactating breast, placenta
What is optimal iodide intake? What are effects of prolonged decrease? (2)
Optimal intake is 100-150 mcg/day
Prolonged decrease results in endemic goiter and cretinism
What is the Wolff-Chaikoff Effect? What is the clinical implication?
Excess iodide transiently inhibits thyroid iodide organification.
In individual with normal thyroid, gland escapes inhibitory effect. But if underlying autoimmune thyroid disease, suppressive effect may persists.
What is the Jod-Basedow Phenomenon? When is it observed?
The Jod-Basedow Phenomenon describes thyrotoxicosis produced by iodine exposure.
It occurs in nodular thyroid glands
Describe the uses for radioiodine. (2)
When is it contraindicated
Can be used in low doses for diagnostic purposes or high doses for therapy
It should not be given to breast-feeding/pregnant women or children
When do you use radioiodine therapy? What is the long-term effect?
Use it in Grave’s disease to create hypothyroidism. The result of radioiodine therapy is necrosis of follicular cells followed by disappearance of colloid and fibrosis of gland
What is amiodarone?
Drug used to treat arrhythmias
Describe the iodine effect of amiodarone: when do you observe it?
In patients with underlying thyroid nodular disease or Grave’s disease, amiodarone results in increased thyroid hormone production.
This is called the iodine effect
Describe the direct toxic effect of amiodarone: when do you observe it?
In patients with normal thyroids it induces destructive thyroiditis–>
There is increased release of preformed thyroid hormone from colloid
When do you use recombinant TSH?
Use in thyroid cancer patients: stimulate thyroid tissue for diagnostic thyroglobulin measurement and radioiodine scanning.
It avoids symptomatic hypothyroidism from radioiodine
When does amiodarone cause hypothyroidism?
In patients with predisposition for hypothyroidism such as Hashimotos
