90 - Oral Hypoglycaemic Agents Flashcards
Blood glucose regulating organ that responds directly to plasma glucose levels, not to hypothalamic-pituitary axis
Pancreas
Role of pancreatic acinar cells
Exocrine.
Release digestive fluid into gut.
Role of pancreatic delta cells
Release somatostatin
Macronutrient, other than carbohydrates, that is affected by DM
Lipid metabolism
Normal shape of blood [insulin] graph over time
Two peaks after ingesting carbohydrates.
First spike, ~5 minutes after ingesting sugar, is quite high.
Then second spike afterwards to regulate breakdown of more complex carbohydrates.
Adverse effect of high levels of sulphonamides
Convulsions, coma, hypoglycaemia.
Stimulates insulin release.
First oral hypoglycaemic
2254RP sulphonamide.
Stimulates insulin release from the pancreas.
Mechanism of sulphonylurea stimulation of pancras
Inhibits ATP-sensitive K+ channel.
Leads to cellular depolarisation, Ca2+ entry.
This stimulates insulin release from pancreas.
How do islet beta cells detect glucose levels?
Have GLUT2 transporter.
Glucose is taken up, converted to ATP.
K+ channel is sensitive to ATP (is closed when ATP binds to it).
Effect of sulphonylureas
Oral hypoglycaemic agents (derived from sulphonamides)
Half life of sulphonylureas
6-24 hours
Why can’t sulphonylureas be used in pregnancy?
Can cross placenta
How are sulphonylureas excreted?
Via kidneys
Adverse effects of sulphonylureas
Weight gain
Hypoglycaemia
Example of a biguanide
Metformin
Actions of metformin
1-4
– Increase insulin-mediated peripheral glucose uptake
– Reduce hepatic glucose production.
– Decrease carbohydrate absorption
– Reduce LDL cholesterol level and triglycerides
Adverse effects of metformin
1-4
– GI disturbances: diarrhoea, nausea, abdominal
discomfort & anorexia
– Lactic acidosis if improperly prescribed
– No weight gain, with possible modest weight loss
– Contraindicated in patients with impaired renal
function
Mechanism of action of metformin
Activates AMP kinase
Drugs used for T2DM with a relative lack of insulin
Drugs which give an increase in insulin in the blood
Sulphonylureas
Meglitinides
Drugs used for T2DM with insulin resistance
Biguanidines Thiazolidinediones (withdrawn in Australia, drug interactions can cause severe liver disease)
Example of an alpha-glucosidase inhibitor
Acarbose
Mechanism of action of alpha-glucosidase inhibitors
Block the enzymes that digest and promote absorption of starches in the small intestine.
Blocks glucose absorption.
Adverse effects of acarbose
1
2
3
– Flatulence or abdominal discomfort
– Loose stools & abdominal pain
– Contraindicated in patients with inflammatory
bowel disease or cirrhosis
When are alpha-glucosidase inhibitors administered?
Only when other options don’t work
Role of incretin hormones
Released from gut, stimulates beta cells to release insulin, inhibits alpha cell glucagon secretion
Enzyme that degrades incretins
DPP-4.
T2DM drugs that affect incretin levels
Dipeptidyl peptidase 4 (DPP4) inhibitors
Role of DPP4 inhibitors
As an adjunct to healthy diet and exercise.
For early T2DM
Adverse effects of DPP4 inhibitors
1-5
- URT infections
- Headaches
- Hypoglycaemia when combined with other T2DM drugs
- Allergic reactions
- Pancreatitis (can be fatal)
Effects of glucagon-like polypeptide receptor agonists
1-4
- Potentiate glucose-mediated insulin secretion
- Suppress glucagon release
- Slow gastric emptying
- Loss of appetite (central action)
Adverse effects of GLP-1 agonists
1-4
- Nausea, vomiting, diarrohea
- Weight loss (anorectic)
- Antibody formation, immune reactions, pancreatitis,
- Endocrine neoplasias (rodents)
Drug class that affects glucose reabsorption
Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors)
