Drugs- Thyroid Diseases (Kinder) Flashcards
oral bisphosphonates,
bile acid sequestrants (cholestyramine),
ciprofloxacin,
proton pump inhibitors, sucralfate,
antacids, bran, soy, coffee
agents that interfere with T4 absorption
interferon
lithium
amiodarone
agents that induce autoimmune thyroid disease with hypo or hyperthyroidism
rifampin, phenobarbital, carbamazepine, phenytoin, HIV protease inhibitors
Agents which increase hepatic metabolism (CYP inducers) and enhance degradation of thyroid hormone:
radiocontrast agents (iopanoic acid, ipodate), amiodarone, beta-blockers, corticosteroids, propylthiouracil
agents which inhibit conversion of T4 to T3 (increase rT3 levels)
what are the 3 thioamides
Methimazole
PTU (propylthiouracil)
What is the MOA of thioamides
prevents thyroid hormone synthesis, inhibits thyroid peroxidase-catalyzed reactions, blocks iodine organification, blocks coupling of iodotyrosines (inhibits the coupling of MIT and DIT to form T3 and T4). Does not affect uptake of iodide by gland.
Additionally–> PTU inhibits peripheral deiodination of T4 to T3
Affect synthesis rather than release
caution in use during pregnancy
what is the onset of action of thioamides
Onset of action is slow and often requires 3-4 weeks before stores of T4 are depleted.
potency and 1/2 life of Methimazole
10x more potent than PTU
drug of choice
t1/2 is 6 hrs.
when is PTU the drug of choice
in first trimester of pregnancy or thyroid storm
otherwise it is second line
t half life is 1.5 hrs
MC ADR of thioamides…
maculopapular rash 4-6 %
at times accompanied by fever and GI distress/nausea
what are some rare ADR’s of thioamides
urticarial rash, vasculitis, lupus-like reaction, lymphadenopathy, hypoprothrombinemia, exfoliative dermatitis, acute arthralgia
cholestatic jaundice (methimazole > PTU), asymptomatic elevations in transaminases
what is the most dangerous complication of thioamides
agranulocytosis (granulocyte count < 500 cells/mm3), infrequent (occurs in 0.1-0.5%) but potentially fatal. Usually rapidly reversible with drug discontinuation but broad spectrum antibiotics may be necessary for complicating infections. Colony stimulating factors (G-CSF) may hasten recovery.
what are the anion inhibitors that competitively inhibit iodine transport mechanisms by blocking iodide uptake
perchlorate (CIO4-)
pertechnetate (TCO4-)
thiocyanate (SCN-)
potassium Iodide MOA
inhibit iodine organification and hormone release;
decrease size and vascularity of hyperplastic gland.
Major action: inhibits hormone release (possibly inhibition of thyroglobulin proteolysis)
what are the therapeutic uses of potassium iodide
thyroid storm
preoperative reduction of hyperplastic gland
(3) Block thyroidal uptake of radioactive isotopes of iodine in a radiation emergency or other exposure to radioactive iodine
iodides should not be used alone b/c the gland will escape the block in 2-8 weeks and withdrawal may cause severe exacerbation of thyrotoxicosis
when should initiation of potassium iodide therapy be started
(5) Initiate after onset of thioamide therapy.
Avoid if treatment with radioactive iodine seems likely.
Potassium iodide Increases intraglandular stores of iodine which may delay thioamide therapy or prevent use of radioactive iodine for several weeks.
what are the ADR’s of potassium iodide
uncommon!
(1) Acneiform rash, swollen salivary glands, mucous membrane ulcerations, conjunctivitis, rhinorrhea, drug fever, metallic taste, bleeding disorders, anaphylactic reactions
avoid in pregnancy - crosses placenta and may cause fetal goiter
MOA of radioactive iodine
effect depends on emission of β rays. Within a few weeks, destruction of thyroid parenchyma evidenced by epithelial swelling and necrosis, follicular disruption, edema, and leukocyte infiltration.
oral administration with sodium solution
stored in storage follicles in thyroid
t1/2 is 5 days
No PAIN!
contraindications of radioactive iodine
pregnancy or breast feeding
thioamides in pregnancy and breast feeding?
(3) Both drugs cross placenta and concentrated in fetal thyroid. Caution use in pregnancy. Risk = fetal hypothyroidism. Pregnancy category D. PTU preferred in 1st trimester as more strongly protein bound; therefore, crosses the placenta less readily. Both drugs considered safe in breast feeding.
overall what is the management of hypothyroidism
b) General treatment strategy: thyroid hormone replacement (levothyroxine drug of choice)
i) Exception – hypothyroidism caused by drugs may potentially be treated with drug removal
when do you administer levothyroxine
on an empty stomach
60 min before meals
4 hours after meals
or at bedtime
Due to many drug interactions/effects separate drug administration times.
when are steady state levels of levothyroxine achieved
6-8 weeks
thyroxine toxicity in children
(1) Children – restlessness, insomnia, accelerated bone maturation and growth
thyroxine toxicity in adults
(2) Adults – increased nervousness, heat intolerance, episodes of palpitations and tachycardia, or unexplained weight loss
what can chronic overtreatment with T4 (especially in elderly) increase risk of?
A-fib
accelerated osteoporosis
what is the medical emergency that is the end-stage of untreated hypothyroidism
myxedema coma
progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death.
how do you treat myxedema coma and what if the patient has adrenal or pituitary insufficiency
(3) Patient must be treated in intensive-care unit (ICU) as intubation and mechanical ventilation may be needed. Drugs must be given IV.
(4) Initiate large loading dose of levothyroxine IV followed by daily maintenance doses.
(5) Hydrocortisone IV may be necessary if patient has adrenal or pituitary insufficiency.
what is the treatment regimen for myxedema and coronary artery disease ?
(1) Correct myxedema cautiously – want to avoid provoking a cardiac event.
Low levels of thyroxine protect heart from increasing demands which could result in angina pectoris, atrial fibrillation, or myocardial infarction (symptoms of elevated thyroid levels).
how do you treat hypothyroidism in pregnancy
(1) Hypothyroid women frequently are relatively infertile until restoration of euthyroid state.
(2) In pregnancy, important to replace thyroid hormones adequately as early development of fetal brain depends on maternal thyroxine.
(a) Many patients will require a dose increase of ~25-30% to maintain euthyroid state.
what are the treatment options for grave’s disease
Antithyroid drugs (Thioamides)
Thyroidectomy
Radioactive Iodine (RAI)
preferred patient population for antithyroid drugs in grave’s disease
young pt’s with small glands and mild disease
antithyroid drugs used in Grave’s disease
effects on thyroid gland?
length of therapy?
(2) Methimazole (preferred) of PTU administered until spontaneous disease remission
(a) Leaves intact gland but requires long period of treatment/observation (12-18 months)
(b) Associated with high rate of relapse (50-70%)
(c) PTU preferred in 1st trimester of pregnancy
preferred patient population for thyroidectomy in grave’s disease or hyperthyroidism of other cause
those with large glands or multi-nodular goiters
what is the treatment regimen prior to thyroidectomy….
and what is the treatment regimen AFTER thyroidectomy
(2) Treat with antithyroid drugs until euthyroid (6 weeks)
(3) For 10-14 days before surgery, administer potassium iodide to diminish gland vascularity
(4) After near total thyroidectomy, 80-90% of patients will require thyroid supplementation
what is the preferred patient population for radioactive iodine treatment in Grave’s or other hyperthyroid issues
most patients over 21 years old
(2) In patients without heart disease, may treat immediately
for patients with heart disease, that are over 21 years old and you are considering radioactive iodine therapy, what must be done prior to administration of this therapy?
(3) For those with heart disease or severe thyrotoxicosis and in the elderly:
(a) Treat with antithyroid drugs until euthyroid
(b) Stop medication 3-5 days before RAI (so as not to interfere with RAI retention), may resume 3-7 days after RAI. Gradually taper antithyroid medication over 4-6 weeks as thyroid function normalizes.
(c) Important to avoid iodides to ensure maximal 131I uptake.
(d) Following RAI, 80% of patients will require thyroid replacement therapy.
adjuncts to antithyroid therapy?
(1) β-blockers can control tachycardia, hypertension, and atrial fibrillation
(2) Diltiazem (calcium-channel blocker) can be used to manage tachycardia in patients in whom β-blockers are contraindicated (asthma, severe/decompensated heart failure)
how do you treat thyroid storm
i) B-blocker to control severe cardiac manifestations (or calcium-channel blocker if contraindicated)
ii) Potassium iodide to prevent release of thyroid hormones from gland
iii) PTU to block hormone synthesis
iv) Hydrocortisone IV to protect against shock (also blocks peripheral conversion of T4 to T3)
v) Supportive therapy to control fever, heart failure, or underlying disease states.’
vi) In rare instances where above measures fail, oral bile acid sequestrants, plasmapheresis, or peritoneal dialysis may lower circulating thyroxine
amiodarone is associated with both hypo and hyperthyroidism….
how is this possible?
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
Causes hypothyroid by:
intrsinic effects of inhibiting 5’-monodeiodination of T4, decreasing T3 production and increasing rT3
Hyperthyroid:
Normal auto-regulation prevents patient from becoming hyperthyroid after iodine load – iodine transport and hormone synthesis transiently inhibited
Those with underlying disease have defects in auto-regulation and may lead to increased hormone production
pt has hypercholesterolemia and is taking a cholestyramine
what can occur?
DDI interaction b/c cholestyramine and levothyroxine
cholestyramine interferes with T4 absorption so T4 is low and TSH goes up
separate administration times
