Endocrine

Question 1

Desmopressin / Vasopressin

Answer 1

Potent analogue of Vasopressin with a longer duration of action and no vasoconstrictor effects.

Question 2

Tolvaptan

Answer 2

Vasopressin V2-receptor antagonist

Question 3

Dexamethasone / Prednisolone / Hydrocortisone / Fludrocortsone
(Steroids)

Answer 3

These corticosteroids exert mainly glucocorticoid effects. They bind to
cytosolic glucocorticoid receptors, which then translocate to the nucleus
and bind to glucocorticoid-response elements, which regulate gene
expression. Corticosteroids are most commonly prescribed to modify
the immune response. They upregulate anti-inflammatory genes
and downregulate pro-inflammatory genes (e.g. cytokines, tumour
necrosis factor alpha). Direct actions on inflammatory cells include
suppression of circulating monocytes and eosinophils. Their metabolic
effects include increased gluconeogenesis from increased circulating
amino and fatty acids, released by catabolism (breakdown) of muscle
and fat. These drugs also have mineralocorticoid effects, stimulating
Na+ and water retention and K+ excretion in the renal tubule.

Question 4

Metformin (Biguanide)

Answer 4

Lowers blood glucose by increasing the response (sensitivity) to insulin. It suppresses hepatic glucose
production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption. It achieves this by diverse intracellular mechanisms, which are incompletely understood. It does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycaemia. It reduces weight gain and can induce weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes mellitus

Question 5

Gliclazide / Glimepiride (Sulphonylureas)

Answer 5

Sulphonylureas lower blood glucose by stimulating pancreatic insulin secretion. They block ATP-dependent K+ channels in pancreatic β-cell membranes, causing depolarisation of the cell membrane and opening of voltage-gated Ca2+ channels. This increases intracellular Ca2+ concentrations, stimulating insulin secretion. Sulphonylureas are only effective in patients with residual pancreatic function. As insulin is an anabolic hormone, stimulation of insulin secretion by sulphonylureas is associated with weight gain. Weight gain increases insulin resistance and can worsen diabetes mellitus in the long term.

Question 6

Thiazolinediones

Answer 6

Thiazolidinediones are insulin sensitisers. They lower blood glucose by activating the gamma subclass of nuclear peroxisome proliferatoractivated
receptors (PPARγ). This induces genes which enhance insulin action in skeletal muscle, adipose tissue and the liver, with increased peripheral glucose uptake and utilisation and reduced hepatic gluconeogenesis. Thiazolidinediones do not stimulate pancreatic insulin secretion, hence do not cause hypoglycaemia. However, they cause weight gain, which can increase insulin resistance.