Lecture 1 - Thyroid Drugs Flashcards by Indy P

What is TSHs direct effect on the follicle cell?

activate NIS to increase iodine intake

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Which conditions/drugs inhibit D1 activity?

acute and chronic illness
caloric deprivation 
malnutrition
glucocorticoids
BB (used in hyperthyroidism) 
amiodarone 
propylthiouracil (used in yperthyroid) 
fatty acids 
selenium deficiency

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TBG

thyroxin binding globulin is the protein that is bound to T4 and T3 in circulation

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What proteins bind to T3 and T4 for transport through circulation?

TBG
transthryetin (TBPA)
albumin

TBG is just to most common

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What drugs can cause an increase in transport proteins?

estrogen
methadone
pregnancy

this means there will be a decrease in free thyroid hormone

this decrease in free hormone will cause the pituitary to increase TSH

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What are the indications for thyroid replacement therapy?

adult hypothyroidism
- usually primary

infantile hypothyroidism
endemic goiter

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What is the drug of choice for hypothyroidism?

Levothyroid sodium - L-thyroxin, T4

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How often is the dosing for T4?

once daily

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What are the adverse effects of T4?

cardiac sxs
angina
palpitations

use with care, particularly in elderly

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Why don’t we use T3 as much as we use T4 for replacement therapy?

more expensive
shorter half life –must be given more often

worse CV risk

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What are the two main antithyroid drugs given for hyperthyroidism?

MMI - methimazole
PTU - propyltiouracil

thioamide class

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What is the MOA of MMI and PTU?

prevent hormone synthesis by inhibiting TPO catalyzed reactions to block iodine organification (binds to and inactivates TPO)

also block coupling of iodotyrosines

PTU has the added effect of blocking D1s conversion of T4 to active T3

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How long does it take for MMI and PTU to take effect?

3 - 4 weeks because you have a storage of hormones

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What are the adverse effects for MMI and PTU?

skin rash, joint pain, agranulocytosis in 0.2% of pts

hepatotoxicity is seen with both but WORSE with PTU

MMI has greater risk of BIRTH defects

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Which has worse hepatotoxicity PTU or MMI?

PTU

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Which has greater risk of birth defects, PTU or MMI?

MMI

Thyroid storm recommended drug?

PTU

Which hyperthyroidism drug is best for pregnancy?

PTU in the first trimester

MMI after that

Anion Inhibitors

antithyroid drugs

thiocyanate competes with iodine for uptake, so there is less iodine taken up

thiocyanate can be a byproduct of smoking

What are the uses of anion inhibitors?

major clinical use for potassium perchlorate is to block thyroidal uptake of iodine in pts with iodine induced hyperthyroidism (ex. amiodarone induced hyperthyroidism)

the use is RARE d.t side effects of aplastic anemia

What are the adverse effects of anion inhibitors?

aplastic anemia

When do you use iodides?

in hyperthyroidism
rare
using the iodine to precipitate the Wolff-Chaikoff effect (suppression of thyroglobulin synthesis and release)

was used when people were exposed to radioactive iodine

What preop treatment is used for thyroidectomy?

thioamide drug till euthyroid (6 weeks)
KI 10 days prior to surgery to reduce size and vascularity
give BB to antagonize catecholamines for symptomatic relief of thyotoxcosis that mimics manifestations of Beta receptor stimulation

MOA of iodines (KI)?

participates the Wolff-Chaikoff effect

I131

Radioactive iodide used to treat thyrotoxicosis MOA: PO, concentrates in thyroid follicle cells, where Beta particles selectively destroy gland w/o injury to adjacent cells pt becomes euthyroid 6-8 weeks

What are the adverse reactions to I131?

eventually causes hypothyoridism | but this is likely part of natural progression of disease

What are contraindications of radioactive iodide?

children and pregnancy no evidence of cancer risk increase with treatment

Enzyme D function

activates T4 into T3 via deionization recall that deionizing you need selenium

What happens with there is an increase in binding protein?

a decrease in "free" hormone (since it's now bound to the binding protein) the pituitary is stimulated by "Free" hormones so it takes this decrease in free hormone as a stimulus to increase TSH and thus increase in free T4

Thioamides

antithyroid drugs PTU and MMI onset of action is slow because mechanism to inhibit hormone synthesis: takes 3-4 weeks to deplete hormone concentrate in thyroid and excreted in urine

What is the treatment course of action for pts with hyperthyroid?

ideally if it is mild to moderate you can manage them with MMI or PTU 60-70% incidence of relapse most will require surgery or radioactive iodine tx at some point

When in hx have they given iodide as a treatment for something?

to compete with the radioactive iodide they gave regular iodide for survivors of churnobel japan tsunami

What are the adverse effects of iodides?

antithyroid drugs uncommon and usually reversible when discontinued acniform rash swollen salivary glands mucous membrane ulcerations Dont use in pregnancy --can cause fetal goiter

What is the treatment prep for a pt whom you will be removing their thyroid?

thioamide drug till euthyroid (~6 weeks) potassium iodide prior to surgery to reduce size and vascularity (aim to reduce surgical risk) give BB to antagonize catecholamines for sxs relief of thyrotoxicosis that mimic manifestations of Beta receptor stimulation you could also use radioactive iodide (concentrates in the follicle cells of the thyroid) to destroy the thyroid (euthyroid in 6-8 weeks)