Thyroid Pharmacology

Question 1

Levothyroxine - Pharmacokinetics

Answer 1

Synthetic T4 - absorbed orally from ileum and colon, best on empty stomach

Reversibly binds to plasma TBG

Converted to T3 in the liver by 5’ de-iodinase

Question 2

Drugs that cause primary hypothyroidism

Answer 2

Lithium
Amiodarine
Phenytoin
Carbamazepine

Question 3

Liothyronine

Answer 3

Synthetic T3

Shorter half-life than levothyroxine - rapid action and shorter duration effect; greater fluctuation in plasma levels between doses

May be added to levothyroxine for persistent symptoms in a T4/T3 ratio of ~10:1

Question 4

Liotrix

Answer 4

4:1 Mixture of T4 to T3

Question 5

Thyroid USP

Answer 5

Porcine thyroid extract containing thyroxine and liothyronine

Disadvantages: Variable T4/T3 ratio, risk of protein antigenicity

Question 6

Treatment of Myxedema Coma

Answer 6

IV loading dose of T4 (Levothyroxine) followed by daily IV dosing

Hydrocortisone to prevent adrenal crisis

Question 7

Drugs that inhibit activating conversion of T4 to T3

Answer 7

Glucocorticoids
Beta blockers
Amiodarone
Propylthiouracil

Useful in thyroid storm

Question 8

Levothyroxine - Adverse Reactions

Answer 8

Toxicity - equivalent to signs and symptoms of hyperthyroidism; can precipitate arrhythmia, angina, or MI in patients with cardiac disease

Drug interactions - precipitates adrenergic effects of sympathomimetics (epi, decongestants)

Question 9

Methimazole - Mechanism

Answer 9

Prevents T4/T3 synthesis by blocking iodine organification and iodotyrosine coupling

Reduces synthesis only, not stores; requires 3-4 weeks to deplete T4 stores and see onset of effect

Effective only in thyrotoxicosis due to excess thyroid hormone production (high RIU)

Question 10

Thionamides - Pharmacokinetics

Answer 10

Methimazole is better absorbed than PTU

Both Methimazole and PTU cross the placenta but PTU crosses to a lesser degree and is less secreted into breast milk

Question 11

Thionamides - Adverse Reactions

Answer 11

Most common (3-12%) - pruritic rash, gastric intolerance, arthralgias

Most dangerous (0.5%) - agranulocytosis, hepatotoxicity

Question 12

Iodides - Mechanism

Answer 12

High doses (> 6mg daily) inhibit hormone synthesis via elevated intracellular [I-] and inhibit hormone release via elevated plasma [I-]

Question 13

Iodides - Clinical Use

Answer 13

Effect occurs rapidly - useful in patients with severe thyrotoxicosis / thyroid storm

Gland ‘escapes’ iodide block in 2-8 weeks; can see exacerbation of thyrotoxicosis upon withdrawal

Can be used to decrease size and vascularity of hyperplastic gland prior to surgery

Question 14

Iodides - Adverse effects

Answer 14

Uncommon and reversible

Rash, rhinorrhea, metallic taste, swollen salivary glands due to selective accumulation of I-

Question 15

Iodides - Agents

Answer 15

SSKI (Potassium Iodide)

Lugol’s solution (Potassium iodide + iodide)

Question 16

Radioactive iodine (131I) - Uses

Answer 16

Administered orally - rapidly absorbed and concentrated in thyroid where release of beta radiation causes slow inflammatory process that destroys thyroid parenchyma

Question 17

Thionamides - Agents

Answer 17

Methimazole

Propylthiouracil

Question 18

Radioactive iodine - Advantages & Disadvantages

Answer 18

Advantage: Easy, cheap, effective, permanent; fewer risks than surgical thyroidectomy, does NOT produce radiation-induced genetic damage

Disadvantages:

Slow onset and time to peak effect (2-6 months)
Risk of radiation thyroiditis due to release of pre-formed thyroid hormone; can cause CV complications
Risk of post-treatment hypothyroidism; 80% will require replacement therapy
Contraindicated in pregnancy

Question 19

Thyroidectomy - Advantages & Disadvantages

Answer 19

Rarely used due to good efficacy / risk profile of radioactive iodine

Advantages: Rapid cure of hyperthyroidism; OK in pregnancy

Disadvantages: Surgical complications; 50-60% require thyroid supplementation after surgery

Question 20

Treatment of thyroid storm

Answer 20

Control of symptoms - Propanolol (IV or po) + Hydrocortisone

Inhibition of release of pre-formed TH - Sodium iodide (IV) or Potassium iodide (po)

Block of conversion of T4 to T3 - Propanolol, PKU, Hydrocortisone