Thyroid Flashcards
What is the MOA of levothyroxine?
Synthetic T4 – direct replacement of T4 in the body
How should levothyroxine be taken?
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)
How long does the onset of levothyroxine take?
PO: 3-5 days
IV: 6-8h
What is the half-life of levothyroxine?
7 days
Does levothyroxine bind to plasma proteins?
Yes, >99%
How is levothyroxine metabolised?
- 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
How is levothyroxine excreted?
Mainly excreted unchanged in urine, metabolites excreted in urine & faeces
What are the adverse effects of levothyroxine?
→ Reduced appetite
→ Anxiety
→ Diarrhoea
→ Difficulty sleeping
→ Hair loss
→ (Rare and serious) heart issues, seizures
→ (Serious) myxoedema coma – severe hypothyroidism
How should levothyroxine be monitored?
→ 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
What is levothyroxine indicated for?
Hypothyroidism
What is carbimazole indicated for?
Hyperthyroidism (before surgical resection)
What is the MOA of carbimazole?
Inhibits thyroid peroxidase to decrease the synthesis of thyroid hormones
(thyroid peroxidase usually iodinates tyrosine residues in thyroglobulin to produce T3 and T4 precursors)
How is carbimazole administered?
PO
How is carbimazole absorbed?
About 90-100% of Carbimazole is rapidly absorbed in the intestines within 15-30 minutes and is rapidly metabolised to its active metabolite methimazole
Does methimazole bind to plasma proteins?
No
How is methimazole distributed?
Concentrated in the thyroid
How is methimazole metabolised?
By CYP450 and FMO enzymes
How are the metabolites of carbimazole excreted?
> 90% excreted in urine as methimazole or its metabolites – the rest in faeces (undergoes enterohepatic circulation as well)
~7% methimazole excreted unchanged in urine
What are the adverse effects of carbimazole?
→ Rashes
→ Joint pain
→ Nausea
→ Jaundice
→ Agranulocytosis (rare)
→ Hypothyroidism (over treatment)
How should carbimazole be monitored?
→ 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
