Pharm: Thyroid Diseases

Question 1

Levothyroxine**

Answer 1

-T4: tx of hypothyroidism

• DOC:
• less potent
• Long t1/2: one dose per day
• lower cost

Question 2

Liothyroxine**

Answer 2

-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

Question 3

Methimazole**

Answer 3

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

Question 4

Propylthiouracil (PTU)**

Answer 4

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)

Question 5

Potassium iodide **

Answer 5

-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

Question 6

what is iodine oxidized by at follicular lumen?

Answer 6

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

Question 7

which agents block iodine transport into thyroid?

Answer 7

thiocyanate, pertechnetate, perchloarate

Question 8

trioiodothyronine

Answer 8

= reverseT3 or rT3

- metabolically inactive form of T4

Question 9

which agents inhibit conversion of T4–>T3?

Answer 9

see low T3, high rT3

• • amiodarone
• iodinated contrast media
• beta blockers
• PTU
• corticosteroids
• severe illness/starvation

Question 10

what activates HPT axis?

Answer 10

acute psychosis and cold epxpsure

Question 11

what inhibits TSH release?

Answer 11

SST
dopamine
large amounts of iodine

Question 12

lag time of TH?

Answer 12

TH is under nuclear receptor activation –> txn and protein synthesis

** hormone actions have a lag time of hours to days after administration

Question 13

which agents increase hepatic metabolism (CYP inducers) and enhance degradation of TH?

Answer 13

• rifampin
• phenobarbital
• phenytoin
• HIV protease inhibitors

Question 14

Which agents interfere with T4 absorption?

Answer 14

• oral bisphosphates
• bile acid sequestrants (cholestyramine)
• ciprofloxacin
• PPI’s
• antacids

Question 15

which agents induce AI thyroid disease w/ hypo or hyperthyroidism?

Answer 15

interferon-alpha, interferon-beta, lithium, amiodarone

Question 16

ADR’s of PTU and methimazole?

Answer 16

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

Question 17

ADR’s of potassium iodide?

Answer 17

Acneiform rash, swollen salivary glands, fever

avoid in pregnancy, crosses placenta and may cause fetal goiter

Question 18

tx of hashimotos?

Answer 18

Levothyroxine - T4

Question 19

Myxedema coma

Answer 19

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

Question 20

tx of Grave’s disease?

Answer 20

1. antithyroid drugs: preferred for patients that are young w/ small glands and mild disease (methimazole preferred unless pregnant)
2. 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
3. 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

Question 21

tx of thyroid storm?

Answer 21

• beta blocker for cardio
• potassium iodide to prevent release of thyroid hormones from gland
• PTU to block hormone synth
• hydrocortisone to protect from shock

Question 22

thyroxine toxicity

Answer 22

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

Question 23

what blocks iodide organification?

Answer 23

methimazole and PTU

- inhibits thyroidal peroxidase-catalyzed reactions and blocks iodide organification; blocks hormone synthesis

Question 24

when is PTU DOC?

Answer 24

1st trimester of pregnancy

thyroid storm: inhibits peripheral deiodination of T4 to T3

Question 25

problems w/ amiodarone?

Answer 25

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

Question 26

cholestyramine?

Answer 26

interferes with T4 absorption

Question 27

TSH receptor activation?

Answer 27

increases adenylyl cyclase and increases camp