Core pharmacology

Class Group

Insulin - Short

Legacy Cicm Level

Level 1

Indications Uses

1. type I diabetes mellitus
2. diabetic emergencies
3. the perioperative control of blood sugar concentration
4. hyperkalaemia and
5. to improve glucose utilization during TPN and
6. in provocation tests for growth hormone.

Chemical Pharmaceutics

Human insulin analogue
Hexomer complexed with zinc that dissociates rapidly to monomers

Presentation

Clear solution
100IU/ml

Main Action

stimulation of carbohydrate metabolism, protein synthesis, and lipogenesis

Mechanism of action

1. Insulin binds the alpha-subunit of insulin receptors → complex is internalized → up regulates tyrosine kinase activity via Beta subunit → insertion of GLUT 4 channels in cell membrane
2. Activates Na/K/ATPase → intracellular K+ shift
3. Direct action on lipoprotein lipase

Onset Peak Duration

5-15min
1-3 hours
3-4 hours

Physiological effects

Metabolic:
- Increases rate of diffusion into cells, especially hepatic (GLUT 4) and increases activity of glucokinase
- Inhibits glycogenolysis and gluconeogenesis
- Stimulate glycogenesis
- Inhibits lipolysis and increases lipogenesis
- Increases active transport of amino acids into cells, stimulates mRNA translation and inhibits catabolism
- Increases K+/Mg uptake into cells

Adverse Effects Toxicity

1. Hypoglycaemia
2. Allergic reactions- local more common. Protaphane may lead to protamine antibodies that only become relevant when large dose protamine administered IV
3. Lipodystrophy
4. Drug interactions- tetracyclines prolong effects of insulin

Absorption

- Inactive when administered orally

Factors affecting exogenous insulin absorption:
- Site of injection (abdominal wall least variable)
- Regional blood flow; Ambient temperature; Exercise
- Depth of injection

Protein binding

Minimal PB (<10%)

Volume of distribution

Vd 0.02L/kg (slightly larger in the diabetic patient).

Metabolism

Rapidly metabolized in liver, kidney and muscle by glutathione insulin transhydrogenase

Excretion

Metabolites excreted in urine.

Route And Dose

SC, IV