Drugs for thyroid disorders

Question 1

What will you see in the thyroid levels of someone w/ hypothyroidism?

Answer 1

Dec T3

Dec T4

Inc TSH

Question 2

What will you see in the thyroid levels of someone w/ hyperthyroidism?

Answer 2

Inc T3

Inc T4

Dec TSH

Question 3

Outline the normal mechanism of thyroid hormone release

Answer 3

Hypothalamus –> TRH –> anterior pituitary —> TSH –> thyroids –> T3/T4 –> target cells

Question 4

Outline the basic phases of thyroid hormone synthesis as well as how T3 and T4 is made (what is combined)

Answer 4

Synthesis = tyrosine –> iodine + thyroid (thyroxine peroxidase) –> mono-iodotyrosine (MIT) –> Di-iodotyrosine (DIT)

MIT + DIT –> T3 triiodothyronine

DIT + DIT –> T4 (thyroxine)

Question 5

What is the role of thyroid hormone in growth?

Answer 5

Growth formation

Bon maturation

Question 6

What is the role of thyroid hormone in CNS?

Answer 6

Maturation of CNS in pregnancy

Question 7

What is the role of thyroid hormone on basal metabolic rate?

Answer 7

Inc Na+K+ ATPase

Inc O2 consumption

Inc heat production

Inc BMR

Question 8

What is the role of thyroid hormone in metbolism?

Answer 8

Inc glucose absorption

Inc glycogenolysis

Inc gluconeogenesis

Inc lipolysis

Inc protein synth & degradation (net catabolic)

Question 9

What is the role of thyroid hormone in cardiovascular system?

Answer 9

Inc CO, HR, Stroke vol –> sensitisation to catecholamines

T3, T4 will cause tachycardia

Question 10

What are the indications of levothyroxine (T4)?

Answer 10

hypothyroidism

goitre

thyroiditis, thyroid cancer

Replacement therapy after thyroid block in hypothyroidism

Question 11

What are the pharmacokinetic properties of levothyroxine (T4)? (T1/2, absorption, SS)

Answer 11

High protein binding in circulation

Long plasma half-life = 6-7 days

SS 4-5 weeks to reach

Taken on empty stomach

Question 12

Why is liothyronine (T3) no commonly used for replacement therapies?

Answer 12

Although 3-4 times more potent

Has short t1/2, requires multiple doses

Higher cost, monitoring is difficult –> need lab tests to see if you’re getting proper levels

Best used for short-term suppression of TSH in emergency - myxoedema coma

Question 13

What is the MOA of radioidine?

Answer 13

Radioisotope = 131I isotope

Emits beta and gamma rays within thyroglobulin

Beta rays –> thyroid follicle –> destruction of follicular cells

dose is not repeated

Question 14

What are the thioureylenes (thioamides) used in hyperthyroidism?

Answer 14

Carbimazole

propylthiouracil

methimazole

Question 15

What is the MOA of thiourea derivates?

Answer 15

Inhibit iodination of tyrosyl residues in thyroglobulin

Inhibit thyroperoxidase catalysed oxidation reactions

Propylthiouracil - reduces de-iodination of T4 to T3 in peripheral tissue (and in cells)

Question 16

What are some pharmacokinetic properties of thioamides? (t1/2, therapuetic effect)

Answer 16

Carbimazole (prodrug)–> methimazole

Class = t1/2 6-15 hrs

Therapeutic effect is delayed due to preformed thyroid hormones
- PTU = 17 weeks for full effect
- Carbimazole = 7 weeks for full effect

Question 17

What are the ADRs seen with thioamides?

Answer 17

Bone marrow suppression –> agranulocytosis

Allergic reactions

- vasculitis, lupus-like syndrome 
- myopathy 
- cholestatic jaundice 

GI upset, headache, arthralgia

Carbimazole crosses placenta –> foetal hypothyroidism

Question 18

What is the MOA of iodine and Lugol solution in hyperthyroidism?

Answer 18

Inhibit H2O2 generation –> inhibit iodination of thyroglobulin

*mainly used in preparation for hyperthyroid surgery or severe thyrotoxicosis

Question 19

What are some ADRs of iodine/iodide/lugol’s solution use in hyperthyroidisms?

Answer 19

Angio-oedema

rashes

drug fever

lacrimation

conjunctivitis

cold-like syndrome