Pharmacology - Thyroid Disorders

Question 1

What is the MOA of levothyroxine?

Answer 1

Synthetic T4 – direct replacement of T4 in the body

Question 2

How should levothyroxine be taken?

Answer 2

PO
- take on empty stomach, 30min before meal (fasting increases absorption + dietary fibre can cause erratic absorption)
- avoid antacids, PPIs and other drugs that affect gastric pH (better absorbed at higher pH, don’t accidentally overdose by F suddenly increasing)
- divalent cations will form non-absorbable chelates (space by 4h apart)

Question 3

What is the bioavailability of levothyroxine?

Answer 3

70-80%

Question 4

How long does the onset of levothyroxine take?

Answer 4

PO: 3-5 days
IV: 6-8h

Question 5

Where is levothyroxine mainly absorbed?

Answer 5

duodenum, jejunum

Question 6

What is the half-life of levothyroxine?

Answer 6

7 days

Question 7

Does levothyroxine bind to plasma proteins?

Answer 7

Yes, >99%

Question 8

How is levothyroxine metabolised?

Answer 8

• Levothyroxine (as T4) can be degraded to form T3 in liver (~80% T3 production)
• Both T3 and T4 metabolised in liver by glucuronidation and sulfation
• Deiodination of T3 and T4 can also occur in kidney

Question 9

How is levothyroxine excreted?

Answer 9

Mainly excreted unchanged in urine, metabolites excreted in urine & faeces

Question 10

What are the adverse effects of levothyroxine?

Answer 10

→ Reduced appetite
→ Anxiety
→ Diarrhoea
→ Difficulty sleeping
→ Hair loss
→ (Rare and serious) heart issues, seizures
→ (Serious) myxoedema coma – severe hypothyroidism

Question 11

How should levothyroxine be monitored?

Answer 11

→ At 6-8 weeks after initiation, measure serum TSH to ensure adequate replacement – once T4 level increases, negative feedback is exerted by the T4 towards the pituitary gland to lower the TSH level
→ Persistently elevated TSH may happen due to inadequate dosing, poor compliance, malabsorption, drug (antacids, PPI, divalent cations) or food interactions

Question 12

What is levothyroxine indicated for?

Answer 12

Hypothyroidism

Question 13

What is carbimazole indicated for?

Answer 13

Hyperthyroidism (before surgical resection)

Question 14

What is the MOA of carbimazole?

Answer 14

Inhibits thyroid peroxidase to decrease the synthesis of thyroid hormones
(thyroid peroxidase usually iodinates tyrosine residues in thyroglobulin to produce T3 and T4 precursors)

Question 15

How is carbimazole administered?

Answer 15

PO

Question 16

How is carbimazole absorbed?

Answer 16

About 90-100% of Carbimazole is rapidly absorbed in the intestines within 15-30 minutes and is rapidly metabolised to its active metabolite methimazole

Question 17

What is the half-life of carbimazole?

Answer 17

(Methimazole) 4-6h

Question 18

Does methimazole bind to plasma proteins?

Answer 18

No

Question 19

How is methimazole distributed?

Answer 19

Concentrated in the thyroid

Question 20

How is methimazole metabolised?

Answer 20

By CYP450 and FMO enzymes

Question 21

How are the metabolites of carbimazole excreted?

Answer 21

> 90% excreted in urine as methimazole or its metabolites – the rest in faeces (undergoes enterohepatic circulation as well)
~7% methimazole excreted unchanged in urine

Question 22

What are the adverse effects of carbimazole?

Answer 22

→ Rashes
→ Joint pain
→ Nausea
→ Jaundice
→ Agranulocytosis (rare)
→ Hypothyroidism (over treatment)

Question 23

How should carbimazole be monitored?

Answer 23

→ Monitor thyroid size and serum TSH level – once thyroid size reduces and normal TSH levels are achieved, carbimazole dose should be titrated down to avoid hypothyroidism
→ Clinical response to carbimazole may take several weeks (3-6 weeks) after initiation to show up as T4 has a long half-life and the thyroid stores of hormone need to be depleted before the effect can show up