Drugs- Thyroid Diseases (Kinder)

Question 1

oral bisphosphonates,
bile acid sequestrants (cholestyramine),

ciprofloxacin,

proton pump inhibitors, sucralfate,

antacids, bran, soy, coffee

Answer 1

agents that interfere with T4 absorption

Question 2

interferon

lithium

amiodarone

Answer 2

agents that induce autoimmune thyroid disease with hypo or hyperthyroidism

Question 3

rifampin, phenobarbital, carbamazepine, phenytoin, HIV protease inhibitors

Answer 3

Agents which increase hepatic metabolism (CYP inducers) and enhance degradation of thyroid hormone:

Question 4

radiocontrast agents (iopanoic acid, ipodate), amiodarone, beta-blockers, corticosteroids, propylthiouracil

Answer 4

agents which inhibit conversion of T4 to T3 (increase rT3 levels)

Question 5

what are the 3 thioamides

Answer 5

Methimazole

PTU (propylthiouracil)

Question 6

What is the MOA of thioamides

Answer 6

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

Question 7

what is the onset of action of thioamides

Answer 7

Onset of action is slow and often requires 3-4 weeks before stores of T4 are depleted.

Question 8

potency and 1/2 life of Methimazole

Answer 8

10x more potent than PTU

drug of choice

t1/2 is 6 hrs.

Question 9

when is PTU the drug of choice

Answer 9

in first trimester of pregnancy or thyroid storm

otherwise it is second line

t half life is 1.5 hrs

Question 10

MC ADR of thioamides…

Answer 10

maculopapular rash 4-6 %

at times accompanied by fever and GI distress/nausea

Question 11

what are some rare ADR’s of thioamides

Answer 11

urticarial rash, vasculitis, lupus-like reaction, lymphadenopathy, hypoprothrombinemia, exfoliative dermatitis, acute arthralgia

cholestatic jaundice (methimazole > PTU), asymptomatic elevations in transaminases

Question 12

what is the most dangerous complication of thioamides

Answer 12

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.

Question 13

what are the anion inhibitors that competitively inhibit iodine transport mechanisms by blocking iodide uptake

Answer 13

perchlorate (CIO4-)

pertechnetate (TCO4-)

thiocyanate (SCN-)

Question 14

potassium Iodide MOA

Answer 14

inhibit iodine organification and hormone release;

decrease size and vascularity of hyperplastic gland.

Major action: inhibits hormone release (possibly inhibition of thyroglobulin proteolysis)

Question 15

what are the therapeutic uses of potassium iodide

Answer 15

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

Question 16

when should initiation of potassium iodide therapy be started

Answer 16

(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.

Question 17

what are the ADR’s of potassium iodide

Answer 17

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

Question 18

MOA of radioactive iodine

Answer 18

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!

Question 19

contraindications of radioactive iodine

Answer 19

pregnancy or breast feeding

Question 20

thioamides in pregnancy and breast feeding?

Answer 20

(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.

Question 21

overall what is the management of hypothyroidism

Answer 21

b) General treatment strategy: thyroid hormone replacement (levothyroxine drug of choice)
i) Exception – hypothyroidism caused by drugs may potentially be treated with drug removal

Question 22

when do you administer levothyroxine

Answer 22

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.

Question 23

when are steady state levels of levothyroxine achieved

Answer 23

6-8 weeks

Question 24

thyroxine toxicity in children

Answer 24

(1) Children – restlessness, insomnia, accelerated bone maturation and growth

Question 25

thyroxine toxicity in adults

Answer 25

(2) Adults – increased nervousness, heat intolerance, episodes of palpitations and tachycardia, or unexplained weight loss

Question 26

what can chronic overtreatment with T4 (especially in elderly) increase risk of?

Answer 26

A-fib

accelerated osteoporosis

Question 27

what is the medical emergency that is the end-stage of untreated hypothyroidism

Answer 27

myxedema coma

progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death.

Question 28

how do you treat myxedema coma and what if the patient has adrenal or pituitary insufficiency

Answer 28

(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.

Question 29

what is the treatment regimen for myxedema and coronary artery disease ?

Answer 29

(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).

Question 30

how do you treat hypothyroidism in pregnancy

Answer 30

(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.

Question 31

what are the treatment options for grave’s disease

Answer 31

Antithyroid drugs (Thioamides)

Thyroidectomy

Radioactive Iodine (RAI)

Question 32

preferred patient population for antithyroid drugs in grave’s disease

Answer 32

young pt’s with small glands and mild disease

Question 33

antithyroid drugs used in Grave’s disease

effects on thyroid gland?

length of therapy?

Answer 33

(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

Question 34

preferred patient population for thyroidectomy in grave’s disease or hyperthyroidism of other cause

Answer 34

those with large glands or multi-nodular goiters

Question 35

what is the treatment regimen prior to thyroidectomy….

and what is the treatment regimen AFTER thyroidectomy

Answer 35

(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

Question 36

what is the preferred patient population for radioactive iodine treatment in Grave’s or other hyperthyroid issues

Answer 36

most patients over 21 years old

(2) In patients without heart disease, may treat immediately

Question 37

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?

Answer 37

(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.

Question 38

adjuncts to antithyroid therapy?

Answer 38

(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)

Question 39

how do you treat thyroid storm

Answer 39

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

Question 40

amiodarone is associated with both hypo and hyperthyroidism….

how is this possible?

Answer 40

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

Question 41

pt has hypercholesterolemia and is taking a cholestyramine

what can occur?

Answer 41

DDI interaction b/c cholestyramine and levothyroxine

cholestyramine interferes with T4 absorption so T4 is low and TSH goes up

separate administration times