Thyroid therapy- hypothyroidism only (Exam 1) Flashcards
Management of hypofunction for thyroid is what?
Hormone replacement (physiologic) therapy for deficiency sates (Hypothyroidism)
Management of hyperfunction of thyroid is what?
Suppression of hormone synthesis or effect (nonhormonal agents) —> hyperthyroidism
The ______ of levothyroxine infroms its pharmacotheraputic use
physiology
What three things inhibit the release of TSH?
- Somatostatin
- Dopamine
- Glucocorticoids
What stimulates the release of TSH?
TRH
What is the major regulated step in the biosynthesis of thyroid hormones?
Uptake of Iodide ion
What can be used to block the uptake of iodide ion?
- SCN
- CLO4
- Iodide itself when given at high concentrations >6mg
What type of symptoms can lithium produce when used as anti-manic therapy?
hypothyroidism
How does the TSH Thyrotropin work?
Stimulates cAMP production which results in increased uptake of iodine and production of thyroid hormones. (lithium blocks this action of TSH)
When would thyrotropin be used?
- in the treatment of metastatic thyroid carcinoma
- it will increase the uptake of radioactive iodine thus destroying the thyroid
What effect does thyroid hyperactivity have on sympathetic nervous system and cardiovascular?
increased SNS activity and increased number of beta-adrenergic receptors and adenylyl cyclase activity on the heart
What is the bioavailability of T4 in the ileum-colon?
65-85%
What is the bioavailability of T3 in the ileum-colon
95%
Treatment of hypothyroidism?
Replacement therapy is appropriate; use of levothyroxine (T4) most satisfactory. For adults, generally start with 50-100 mcg, working up to 1.6-1.8 mcg/kg/day
Is the dose of levothyroxine greater for infants or adults?
infants, they can go up to 15mcg/kg and should be monitored for development
Out of the three options below, who would get the lowest dose of levothyroxine (T4)
A. Infants
B. Adults
C. Elderly
The elderly, they can go as low as 0.5mcg/kg
Why would pregnancy require an increased dose of to treat hypothyroidism?
because of increased levels of TBG (via increased estrogen). This decreases free T3-T4
also because of increased placental metabolism of T3-T4
What type of condition would make you stop and use caution when prescribing something to increase thyroid function?
an underlying cardiac disease
is Myxedema coma a medical emergency? How do you treat it?
- Yes
- Large doses of T4 required with IV loading dose of T4 followed by daily IV dosing (can use T4 and T3 together or just T3 alone)
- Hydrocortisone may be required to prevent adrenal crisis because thyroid hormone may increase its metabolism
True or false: Levothyroxine has a large therapeutic index?
false it has a narrow one
How should levothyroxine be taken?
Levothyroxine should be taken alone on an empty stomach, with a full glass of water, at least 30 minutes before breakfast
How does one manage avoiding absorption impairment of levothyroxine caused by other drugs?
Managed by spacing levothyroxine dose 2 hours before or 4-6 hours after interacting drug.
What drugs impair levothyroxine absorption?
- metal ions (antacids-Ca++-Fe++)
- ciprofloxacin
- bile acid sequestrants
- raloxifene
- sucralfate
- dietary fiber
- soy
Which form of the thyroid hormone has metabolic activity? Bound or unbound?
only the unbound form.
Changes with what will have major effects on total thyroid serum hormone levels?
Changes in either the concentrations of binding proteins OR binding affinity of hormone for protein
What drugs cause an increase in binding of the thyroid protein?
- Estrogens
- SERMs
- Tamoxifen
What drugs cause a decrease in binding of thyroid hormone?
- Salicylates
2. Antiseizure meds (phenytoin, carbamazepine)
True or false: laboratory tests that measure total hormone levels can be misleading?
True
T3 80% utilized by _________ ________ is derived from T4 deiodination in the _______
- peripheral tissues
2. Liver
T3 in brain and pituitary derived by _______ deiodination?
intracellular
T4 is converted into T3 the active hormone by an activating enzyme. Drugs can INHIBIT this enzyme. Which ones do this?
- Glucocorticoids
- Beta-Blockers
- Amiodarone
- PTU (propylthiouracil)
Metabolic clearance rates may be ______ in hyperthyroidism and ________ by hypothyroidism?
- Increased
2. Decreased
Metabolic clearance rates my also be increased with _______ enzyme induction (carbamazepine, digoxin, phenytoin, rifampin)
CYP450 our good friend
What is the half life of T4 and T3?
T4 is 7 days
T3 is 1 day
What is the major factor for the difference in the half lives?
Degree of protein binding.
Remeber free T4 is .04% where as free T3 is .4% alot less bound to proteins
Because T4 has a long half live it allows for what kind of dosing?
once daily dosing and can miss a dose or so and still maintain therapeutic levels
For the management of hypothyroidism there are four drug options. what are they?
- Levothyroxine (synthetic T4)
- Liothyronine aka cytomel (synthetic T3)
- Liotrix aka thyrolar (4:1 mixture of T4 and T3)
- Thyroid USP aka armour thyroid (variable T4/T3 ratio
Between synthetic T3 and T4 which one is the preferred preparation of choice for thyroid replacement?
synthetic T4
When should a thyroid function test be checked after a change in levo product formulation?
6 weeks after
When would one expect to se resolution of symptoms from hypothyroidism if being treated with levo?
- within 2-3 weeks
- requires 6-8 weeks of maintenance dose to approach steady-state plasma levels
Why is Liothyronine not recommended for routine replacement?
this is because it has a short half life which means great Cp fluctuations between doses
It also require alot of green backs
If someone has a cardiac disease should you use Liothyronine?
No because it is synthetic T3 which puts it at a greater risk of cardiotoxicity
Which has a greater affinity for thyroid hormone receptors T4 or T3
T3 for sure
Liotrix what you need to know.
Rarely required, not recommended
More expensive
combined therapy may cause increased incidence of low TSH concentrations and increased markers of bone turnover
Currently is Thyroid USP (Armour Thyroid) recommended for use in hypothyroidism?
nope
________ is dessicated porcine thyroid extract containing T3 and T4
Thyroid USP
Disadvantages of Thyroid USP?
- Variable T4/T3 ratio and content that may produce unexpected toxicities
- Protein antigenicity
- Product instability
