Drug Classification: Thyroid

Thyroxine

UNDER REVIEW (September 2016)

Mechanism of Action:

Thyroxine (T4) is produced by iodination of tyrosine residues on thyroglobulin at the apical membrane of thyroid follicular cells. They are stored in the lumen of these cells until stimulation for release by thyroid-stimulating hormone (TSH). Metabolism of T4 in the target cells and the liver produces triiodothyronine (T3) which is more active physiologically but has a shorter half-life. Thyroid hormones T3 and T4 exert their actions by binding to thyroid hormone receptors and encouraging transcription of necessary genes. They are involved in controlling the metabolism of substrates (carbohydrates, fats and proteins) and increase the basal metabolic rate. In children, they are also involved in growth.

Lecture and CAL materials:

Carbimazole

UNDER REVIEW (September 2016)

Mechanism of Actions:

Use in treatment of hyperthyroidism. Interferes with the endogenous synthesis of thyroid hormones. Carbimazole acts to prevent the conversion of iodine to its useable form. Carbimazole also acts to block the combination of converted iodine with other components to form thyroid hormones. This results in a decreased production of thyroid hormones.

Lecture and CAL materials:

Propranolol

Mechanism of Action:

Beta-adrenoreceptor antagonist (beta blocker – non-selective; Class 2 antiarrhythmic).

Indications:

  • For cardiovascular indications, supplanted by cardioselective (beta 1) beta blockers such as bisoprolol
  • Essential tremor
  • Thyrotoxic crisis
  • Prophylaxis of migraine – though cardioselective beta blockers are probably as effective and therefore preferred

Beta 1 adrenoreceptors may be occupied by the endogenous ligand, noradrenaline [norepinephrine, NE], released from sympathetic [adrenergic] nerve endings; or by circulating adrenaline [epinephrine, E] or NE, released into blood from the adrenal medulla.

The receptor acts via G-protein-coupled activation of adenylate cyclase, which increases levels of cAMP, leading to activation of protein kinase A (PKA). In the heart PKA phosphorylates Ca2+ channels, increasing inward Ca2+ current and hence force of contraction. NE and E also increase rate and electrical excitability.

Non-selective beta blockers such as propranolol occupy the beta adrenoceptors and prevent their activation by NE/E. Beta blockade slows pacemaker activity, increases atrioventricular refractory period, reducing heart rate, force of contraction and electrical excitability of the heart. Also blocks beta 2 adrenoceptors.

Beta blockers also reduce sympathetically-mediated renin release.

Lecture and CAL materials: