Drugs- Thyroid Diseases (Kinder) Flashcards Preview

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Flashcards in Drugs- Thyroid Diseases (Kinder) Deck (41)
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1
Q

oral bisphosphonates,
bile acid sequestrants (cholestyramine),

ciprofloxacin,

proton pump inhibitors, sucralfate,

antacids, bran, soy, coffee

A

agents that interfere with T4 absorption

2
Q

interferon

lithium

amiodarone

A

agents that induce autoimmune thyroid disease with hypo or hyperthyroidism

3
Q

rifampin, phenobarbital, carbamazepine, phenytoin, HIV protease inhibitors

A

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

4
Q

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

A

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

5
Q

what are the 3 thioamides

A

Methimazole

PTU (propylthiouracil)

6
Q

What is the MOA of thioamides

A

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

7
Q

what is the onset of action of thioamides

A

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

8
Q

potency and 1/2 life of Methimazole

A

10x more potent than PTU

drug of choice

t1/2 is 6 hrs.

9
Q

when is PTU the drug of choice

A

in first trimester of pregnancy or thyroid storm

otherwise it is second line

t half life is 1.5 hrs

10
Q

MC ADR of thioamides…

A

maculopapular rash 4-6 %

at times accompanied by fever and GI distress/nausea

11
Q

what are some rare ADR’s of thioamides

A

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

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

12
Q

what is the most dangerous complication of thioamides

A

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.

13
Q

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

A

perchlorate (CIO4-)

pertechnetate (TCO4-)

thiocyanate (SCN-)

14
Q

potassium Iodide MOA

A

inhibit iodine organification and hormone release;

decrease size and vascularity of hyperplastic gland.

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

15
Q

what are the therapeutic uses of potassium iodide

A

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

16
Q

when should initiation of potassium iodide therapy be started

A

(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.

17
Q

what are the ADR’s of potassium iodide

A

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

18
Q

MOA of radioactive iodine

A

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!

19
Q

contraindications of radioactive iodine

A

pregnancy or breast feeding

20
Q

thioamides in pregnancy and breast feeding?

A

(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.

21
Q

overall what is the management of hypothyroidism

A

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

22
Q

when do you administer levothyroxine

A

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.

23
Q

when are steady state levels of levothyroxine achieved

A

6-8 weeks

24
Q

thyroxine toxicity in children

A

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

25
Q

thyroxine toxicity in adults

A

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

26
Q

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

A

A-fib

accelerated osteoporosis

27
Q

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

A

myxedema coma

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

28
Q

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

A

(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.

29
Q

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

A

(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).

30
Q

how do you treat hypothyroidism in pregnancy

A

(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.

31
Q

what are the treatment options for grave’s disease

A

Antithyroid drugs (Thioamides)

Thyroidectomy

Radioactive Iodine (RAI)

32
Q

preferred patient population for antithyroid drugs in grave’s disease

A

young pt’s with small glands and mild disease

33
Q

antithyroid drugs used in Grave’s disease

effects on thyroid gland?

length of therapy?

A

(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

34
Q

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

A

those with large glands or multi-nodular goiters

35
Q

what is the treatment regimen prior to thyroidectomy….

and what is the treatment regimen AFTER thyroidectomy

A

(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

36
Q

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

A

most patients over 21 years old

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

37
Q

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?

A

(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.

38
Q

adjuncts to antithyroid therapy?

A

(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)

39
Q

how do you treat thyroid storm

A

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

40
Q

amiodarone is associated with both hypo and hyperthyroidism….

how is this possible?

A

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

41
Q

pt has hypercholesterolemia and is taking a cholestyramine

what can occur?

A

DDI interaction b/c cholestyramine and levothyroxine

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

separate administration times