The pharmacology of insulin Flashcards
What are the normal ranges for blood glucose?
3-8mmol/L
What are the ranges for hypo and hyper glycaemia?
hypo = 10mmol/L
What are the stages of hyperglycaemia?
Food intake > rise in blood glucose > insulin release > insulin action: liver, muscle, CNS > lowers blood glucose
What are the stages in hypoglycaemia?
Fasting > fall in blood glucose > glucagon release> endogenous glucose production > raises blood glucose
Where is insulin and glucagon released from?
Pancreatic islets of langerhans - insulin = B cells, Glucagon = a cells.
How is insulin released?
Food intake > digestion > glucose uptake by B cells > inhibition of K channels > depolarisation of cell > calcium influx > insulin release.
What are the functional effects of insulin?
Convert glucose into glycogen and fats. Convert amino acids into proteins. Glucose and amino acid transport into cells.
What does insulin act on to lower blood sugar?
Glut4
What is T1DM?
Caused by destruction or damage to B cells. An autoimmune disease.
What is T2DM?
A disorder of epidemic proportions. Risk factors include: ageing, obesity, ethnicity, family history. Genetic and environmental predisposition.
What is the treatment plan for T1DM?
lifelong insulin, healthy diet, regular exercise.
What is the treatment plan for T2DM?
Lifestyle changes or hypoglycaemic therapy and/or insulin.
What are the short duration insulin therapies?
Insulin aspart, insulin glulisine, insulin lispro (s/c/I.v). Rapid onset - 30-60 mins. Duration of 8 hours.
What are the intermediate insulin therapies?
insulin detemir, insluin glargine, insulin zinc suspension. Onset o 1-2 hours, duration of 16-35 hours.
What are biphasic insulin preparations?
Mixture of intermediate and fast acting. rapid onset and long-lasting actions. Biphasic insulin aspart.
How is insulin administered?
SC Injection 3-4 times daily.
What is glucagon therapy used for?
First-aid treatment for severe hypoglycaemia when oral glucose is not possible.
What do secretagogues do?
Treat T2DM. Antagonists of the K channel. Boost insulin release.
What are the 2 types of secretagogues?
Sulphonylureas. Meglitinides.
What do secretagogues II do?
Peptide-agonists of the GLP-1 receptor and boost insulin release.
What are the 2 types of secretagogues II?
Exenatide, Liraglutide.
What are the side effects of secretagogues II?
GI disturbances, N&V, diarrhoea, dyspepsia, abdo pain, GORD, decreased appetite, dizziness, agitation, increased sweating
What do secretagogues III do?
Inhibitors of DPP-4 and raise the half-life of serum GLP-1.
What are the names of some secretagogues III?
Gliptins, Sitagliptin, Vildagliptin.
What is Diazoxide?
Hyperglycaemia therapy. Agonist of the K channel - inhibition of insulin release.
What are the side effects of diazoxide?
ANorexia, N&V, hypotension, oedema, tachycardia, arryhtmias.
What are insulin sensitisers?
Improve the sensitivity of target organs to insulin. Two types - Biguanides which activate enzymes and Thiazolidinedoines which modify the transcription of genes.
Which enzyme doe Biguanides activate?
AMP - protein kinase (AMPK)
What are the two modes of action of Biguanides?
Prevents hepatic production of glucose. Overcomes insulin resistance by improving insulin sensitivity.
What is the most common type of Biguanides?
Metformin.
What does thiazolidinediones act on?
Activates PPAR for transcription of insulin-sensitive genes.
What is an example of a thiazolidinedione?
Rosiglitizone
