Diabetes pharmacology Flashcards
Which drug is a first generation sulphonylurea?
Tolbutamide
Which drugs are second generation sulphonylureas?
Glibenclamide
Glipizide
How do sulphonylureas stimulate insulin release?
Displaces the binding of ADP-Mg2+ from the SUR1 subunit, closing the KATP channel, allowing the membrane depolarisation to occur that stimulates insulin release
What is the difference between first and second generation sulphonylureas?
Second are more potent and longer acting
What is the disadvantageous side effect of sulphonylureas?
Weight gain
In which patients is the risk of hypoglycaemia caused by sulphonylureas increased?
Elderly
Impaired hepatic/renal function
Which drugs are examples of glinides?
Repaglinide
Nateglinide
How do glinides work?
Binds to SUR1 subunit at a benzamino site, closing the KATP channel and triggering insulin release
Are sulphonylureas or glinides more likely to cause hypoglycaemia?
Sulphonylureas
When are glinides taken and why?
Before meals
Combats post-prandial rise in glucose
What do glucagon-like peptide 1 (GLP1) and glucose dependant insulinotropic peptide (GIP) do and when are they released?
Released in response to ingestion of food
GLP-1 and GIP stimulate insulin secretion from pancreatic beta cells and delay gastric emptying
GLP-1 decreases glucagon release from pancreatic alpha cells
Which drugs mimic the action of GLP-1?
Incretin analogues
Which drug is an incretin analogue?
Extenatide
What are the effects of incretin analogues?
Increases insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
Decreases appetite
What are some of the advantages of using incretin analogues?
Cause modest weight loss
Reduce hepatic fat accumulation
How is extenatide administered?
Subcutaneously twice daily
What are some of the side effects of extenatide?
Nausea
Hypoglycaemia
Pancreatitis
How do DPP-4 inhibitors/gliptins work?
Inhibit the actions of DPP-4 (a GLP-1 and GIP inhibitor), prolonging the effects of GLP-1 and GIP
What are some examples of some gliptins?
Sitagliptin
Saxigliptin
Vildagliptin
What are some of the advantages of using gliptins?
Weight neutral
Generally well tolerated
No hypoglycaemia
How does acarbose work?
Inihbit alpha-glucosidase, stopping the breakdown of carbohydrates into absorbable glucose form
More carbohydrate is excreted in stools
In which patients is acarbose used?
Patients whose T2DM is inadequately controlled by lifestyle changes and drugs
What are the side effects of acarbose?
Flatulence Bloating Abdominal pain Loose stools Diarrhoea
Which is the first line drug treatment for obese T2DM patients?
Metformin
How does metformin work?
Reduces hepatic gluconeogenesis
Reduces carbohydrate absorption
Increases fatty acid oxidation
Increases glucose uptake and utilisation in skeletal muscles
What are the advantages of using metformin?
Causes weight loss
Does not cause hypoglycaemia
Prevents hyperglycaemia
Can be used with other therapies
When must use of metformin be stopped?
When kidney function declines
GFR <30, metformin stopped
What are some of the adverse affects of metformin?
GI upsets (diarrhoea/nausea/anorexia) (Rarely) lactic acidosis
Which is the only thiazolidinedione licenced for use in the UK?
Pioglitazone
How do thiazolidinediones work?
Enhance the action of insulin at target tissues Promotes the genetic expression of: Lipoprotein lipase Fatty acid transport protein GLUT4
What are the desirable effects of thizolidinediones?
Promote fatty acid uptake and storage in adipocytes, rather than skeletal muscle and liver
Reduced hepatic glucose output
What are the adverse effects of thiazolidinediones?
Weight gain
Fluid retention (Na+ reabsorption at kidney encouraged)
Increases incidence of bone fractures
Which is the only Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor licesnced for use in the UK?
Dapagliflozin
How do sodium-glucose cotransporter-2 (SGLT2) Inhibitors work?
Selectively blocks the reabsorption of glucose at the proximal tubule of the nephron to purposefully cause glucosuria
This reduces blood glucose and can cause some weight loss
What is the required treatment for type 1 diabetes?
Immediate insulin therapy
What are the aims of insulin therapy for T1DM?
Avoid hypoglycaemia
Reduce hyperglycaemia
Reduce chronic complications
Which insulins are examples of rapid acting analogues?
Humalog* (insulin lispro)
NovoRapid
Apidra
Which insulins are short acting?
Humulin S (Human insulin)
Actrapid
Insuman Rapid
Which insulin is a long acting analogue?
Lantus
Levemir
Which insulin regimen aims to mimic normal endogenous insulin production?
Basal bolus regimen
What is involved in the basal bolus insulin regimen?
One long acting injection to maintain insulin levels
Three rapid acting injections before meals to combat post-prandial rise in glucose
How is initial insulin requirement in basal bolus regimen calculated?
0.3 units/kg body weight Divide 50% basal 50% prandial e.g. 60kg => 18 units 9 units basal 3/3/3 units prandial
