Pharm: Thyroid Diseases Flashcards
Levothyroxine**
-T4: tx of hypothyroidism
- DOC:
- less potent
- Long t1/2: one dose per day
- lower cost
Liothyroxine**
-T3: tx of hypothyroidism
- 3-4x more potent, better bioavailability
- not recommended for routine replacement, reqs. mutliple dosing per day
- higher cost
- very potent, should be avoided in those with cardiac disease
- best used in short term suppression of TSH
Methimazole**
thioamide DOC: tx hyperthryoidism
MOA: affects synthesis of TH! prevents TH synthesis, inhibits TPO rxns. Does not affect iodide uptake by gland
- onset of action is slow: takes 3-4 weeks for T4 stores to be depleted
** DOC: 10x more potent than PTU, given once perday
Propylthiouracil (PTU)**
thioamide-Tx hyperthyroidism
MOA: Affects synthesis of TH: prevents TH synthesis, inhibits TPO rxns. Does not affect iodide uptake by gland
** additionally: inhibits peripheral deiodination of T4 to T3
- onset of action is slow: takes 3-4 weeks for T4 stores to be depleted
** Not as potent as methimazole - DOC for pregnancy (used in first trimester - more strongly binds protein and crosses placenta less readily)
Potassium iodide **
-Tx for hyperthryoidism
MOA: inhibits iodine organification and hormone release; decrease size and vascularity of hyperplastic gland.
Major action: inhibits hormone release
Use:
- thyroid storm, preop reduction of hyperplastic gland, block uptake of radioactive isotopes
- should never be used on their own
what is iodine oxidized by at follicular lumen?
thyroidal peroxidase (TPO) - TPO is blocked by high levels of intrathyroidal iodine and thioamide drugs
- iodine then iodinates tyrosine residues within thyroglobulin –> MIT And DIT
which agents block iodine transport into thyroid?
thiocyanate, pertechnetate, perchloarate
trioiodothyronine
= reverseT3 or rT3
- metabolically inactive form of T4
which agents inhibit conversion of T4–>T3?
see low T3, high rT3
- amiodarone
- iodinated contrast media
- beta blockers
- PTU
- corticosteroids
- severe illness/starvation
what activates HPT axis?
acute psychosis and cold epxpsure
what inhibits TSH release?
SST
dopamine
large amounts of iodine
lag time of TH?
TH is under nuclear receptor activation –> txn and protein synthesis
** hormone actions have a lag time of hours to days after administration
which agents increase hepatic metabolism (CYP inducers) and enhance degradation of TH?
- rifampin
- phenobarbital
- phenytoin
- HIV protease inhibitors
Which agents interfere with T4 absorption?
- oral bisphosphates
- bile acid sequestrants (cholestyramine)
- ciprofloxacin
- PPI’s
- antacids
which agents induce AI thyroid disease w/ hypo or hyperthyroidism?
interferon-alpha, interferon-beta, lithium, amiodarone
ADR’s of PTU and methimazole?
most common: maculopapular rash/ GI distress/ nausea
*** PTU Severe: severe hepatitis and death
Most dangerous complication: agranulocytosis - tx with G-CSF and take off of drugs
ADR’s of potassium iodide?
Acneiform rash, swollen salivary glands, fever
avoid in pregnancy, crosses placenta and may cause fetal goiter
tx of hashimotos?
Levothyroxine - T4
Myxedema coma
end stage of untreated hypothyroidism - assoc. w/ weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, shock and death
pt. must be treated in ICU
initiate large loading dose of levothyroxine
tx of Grave’s disease?
- antithyroid drugs: preferred for patients that are young w/ small glands and mild disease (methimazole preferred unless pregnant)
- thyroidectomy: preferred for those w/ large glands/MNG’s
- tx w/ antithyroid drugs until euthyroid
- administer potassium iodide to dimish gland vascularity before surgery
- many will require thyroid supplementation after surgery - Radioactive Iodine (RAI)
- preferred tx for patients over 21 y/o
- may tx immediately if no heart disease
- if have heart disease tx w/ drugs until euthyroid, then use RAI
- many will require thyroid supplementation
Adjuncts:
- Beta-blockers: can control tachycardia, HTN, A fib
- Diltiazem used for those with asthma
tx of thyroid storm?
- beta blocker for cardio
- potassium iodide to prevent release of thyroid hormones from gland
- PTU to block hormone synth
- hydrocortisone to protect from shock
thyroxine toxicity
Children – restlessness, insomnia, accelerated bone maturation and growth
Adults – increased nervousness, heat intolerance, episodes of palpitations and tachycardia, or unexplained weight loss
Chronic overtreatment with T4 (especially in elderly) can increase risk of atrial fibrillation and accelerated osteoporosis
what blocks iodide organification?
methimazole and PTU
- inhibits thyroidal peroxidase-catalyzed reactions and blocks iodide organification; blocks hormone synthesis
when is PTU DOC?
1st trimester of pregnancy
thyroid storm: inhibits peripheral deiodination of T4 to T3
problems w/ amiodarone?
associated with: both hypo- and hyperthyroidism
** marked increase in iodine : those with underlying disease have defects w/ autoregulation (thus see more rT3 and less T3)
Contains two iodine atoms
~3 mg of inorganic iodine released after liver metabolism for every 100 mg dose
Average iodine intake in typical diet = 0.3 mg/day
Thus, 6 mg iodine released with a 200 mg dose will markedly increase iodine load
cholestyramine?
interferes with T4 absorption
TSH receptor activation?
increases adenylyl cyclase and increases camp
