Core pharmacology

Class Group

Thyroid hormone

Legacy Cicm Level

Level 3

Indications Uses

1. hypothyroidism
2. myxoedema coma, and
3. goitre

Chemical Pharmaceutics

iodine-containing amino acid derivatives of thyronine.

Presentation

Levothyroxine tablets - 25/50/100 micrograms of levothyroxine sodium
Triiodothyronine: 20mcg tablets or while lyophilized powder for reconstitution in water

Main Action

Modulation of growth and metabolism

Mechanism of action

combine with a ‘receptor protein’ within the cell nucleus
- thereby activate the DNA transcription process
- leading to an increase in the rate of RNA synthesis and a generalized increase in protein synthesis

Onset Peak Duration

Levothyroxine: 24hr latency, peak 6-7 days

Triiodothyronine: acts in 6hrs, peak 24hrs

Physiological effects

CVS:
- Positively inotropic, chronotropic (Beta)
- inc SBP, dec DBP
- Vasodilation from peripheral O2 consumption

RS: Inc rate and depth of respiration from inc BMR

CNS: Stimulatory: tremor, hyperreflexia

GI: Inc Appetite, Secretory activity and motility
GU: Control of sexual function and menstruation
Metabolic: promote gluconeogenesis and inc mobilization of glycogen stores
Lipolysis, inc FFA
Inc Protein synthesis

Adverse Effects Toxicity

Thyrotoxicosis

Absorption

PO BA 100%

Protein binding

Thyroid-binding globulin
Levo: 99.97%
Tri: 99.5%

Volume of distribution

Levo 0.2 L/kg
Tri: 0.5 L/kg

Metabolism

35% of Levothyroxine → Triiodothyronine (liver, kidney), inactive T3
Conjugate to glucuronide and sulfate → bile
Some Enterohepatic recirc

Excretion

20-40% faeces unchanged

Clearance

Levo: 1.7 ml/min
Tri: 17 ml/min

Half-life

Levo: 6-7 days
Tri: 2 days

Special Points

- Increase warfarin effect
- Beta agonists – inhibit conversion of levothyroxine to triiodothronine

Route And Dose

PO Levothyroxine: 25-300mcg daily in divided doses – titrated to response and TFTs

Triiodothyronine: PO 10-60mcg/day
IV 5-20mcg 4-12hrly