Drug Classification: Diabetes

Glucagon

UNDER REVIEW (September 2016)

Mechanism, of Action:

Glucagon is a natural polypeptide hormone that is made by alpha cells of the pancreatic islets of Langerhans. It acts at endogenous G-protein coupled receptors where it activates the enzyme adenylate cyclase which manufactures cAMP (cyclical AMP), which activates protein kinase A (cAMP-dependent protein kinase), which in turn activates phosphorylase B kinase, which in turn, phosphorylates phosphorylase B. Phosphorylase B is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers in liver and muscle. In addition to glycogenolysis, glucagon has other catabolic actions including hepatic gluconeogenesis (the breakdown of protein and other substrates to make glucose) and lipolysis (breakdown of fat in adipose tissue as an alternative energy source to glucose). Biologically it is the counteracting hormone to insulin (which works to depress plasma glucose levels and remove it into storage). Glucagon is important in preventing hypoglycaemia and maintaining energy levels and glucose supply to important tissues such as the brain.

Lecture and CAL material:

Glucose

UNDER REVIEW (September 2016)

Mechanism of Action:

Used to treat hypoglycaemia. Natural dietary constituent. Replenishes glucose supplies to vital organs and helps to increase liver stores.

Lecture and CAL materials:

Metformin

UNDER REVIEW (September 2016)

Mechanism of Action:

Biguanide drug (only one available). Mode of action is uncertain. There is evidence that it acts by activating AMP-activated protein kinase (AMPK) in liver cells, leading to increased fatty acid oxidation and glucose uptake by cells and decreased lipogenesis and hepatic glucose production. Its net effect in an improvement in insulin resistance.Decreases gluconeogenesis and increases peripheral utilisation of glucose. It acts only in the presence of endogenous insulin and so is only effective if there are some residual functioning pancreatic islet cells.

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Gliclazide

UNDER REVIEW (September 2016)

Mechanism of Action:

Gliclazide is a short-acting sulfonylurea, which stimulates secretion of endogenous insulin from beta-cells in the pancreas. It inhibits the K+/ATP channel, thereby mimicking the normal response to ingestion of food. The metabolism of glucose causes accumulation of ATP inside beta-cells, which blocks K+/ATP, depolarizing the membrane and causing calcium to enter the cell. This leads to secretion of insulin from insulin-containing vesicles (it is an ‘insulin secretagogue’).

Lecture and CAL materials:

Insulin

UNDER REVIEW (September 2016)

Mechanism of Action:

A peptide hormone, normally secreted from the beta cells of the islets of Langerhans in the pancreas, which is administered for treating diabetes mellitus type 1 (type I), also for some cases of type 2 (type II). Acts on the insulin receptor.The actions of insulin on the global human metabolism level include: cellular intake of certain substances, most prominently glucose – increase of DNA replication and protein synthesis – modification of the activity of numerous enzymes (allosteric effect).

 

Simvastatin

Indications

  • Treatment of hypercholesterolaemia or mixed dyslipidaemia
  • Reduction of cardiovascular morbidity and mortality in patients with a risk
  • Management of peripheral vascular diseases

Mechanism of Action

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. HMG-CoA reductase is the rate-determining enzyme in cholesterol synthesis. Reduced intracellular cholesterol concentrations activate a cellular signaling cascade that results in the up-regulation of the gene coding for synthesis of LDL receptors. Increased LDL receptors (mainly in hepatocytes) cause increased LDL uptake into cells, resulting in lower plasma LDL levels. Simvastatin is an inactive pro-drug which is metabolized to its active form in the liver.

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