Type II Diabetes: Oral Glycaemic Agents Flashcards
Which endocrine gland is not regulated by a hypothalamic-pituitary loop?
Pancreas
What does the pancreas directly respond to?
Plasma glucose levels
What are the backups for eliciting an insulin-like response?
Sympathetic > adrenal medulla > adrenaline
Anterior pituitary > adrenal cortex > cortisol
What are the exocrine cells of the pancreas?
Acinar cells
What are the endocrine cells of the pancreas?
Islets of Langerhans
What cells in the islets of Langerhans secrete glucagon?
Alpha cells
What cells in the islets of Langerhans secrete insulin?
Beta cells
What cells in the islets of Langerhans secrete somatostatin?
Delta cells
What are the responses to insulin after a meal in someone with a relative lack of insulin?
Can have higher than normal basal rate
Food taken
No initial spike
Second maintained release sub-normal to normal
What are the therapeutic lifestyle changes that can be made in type 2 diabetes?
Aim for ideal body weight - Restrict refined sugars - Reduce saturated fats Adequate exercise Stop smoking Reduce alcohol Treat hypertension and lipidaemias
What do sulfonylureas do?
Increase insulin secretion from beta cells > restore phase 1 spike in insulin
How do sulfonylureas work?
Inhibit ATP-gated K channels
What are the pharmacokinetics of sulfonylureas?
Oral absorption
Half-life = 6-24 hours
Excreted via kidneys
Why aren’t sulfonylureas used in pregnancy?
Cross placenta
What are the adverse effects of sulfonylureas?
Hypoglycaemia
Weight gain
What is the drug class of metformin?
Biguanides
What does metformin do?
Increases insulin-mediated peripheral glucose uptake
Reduces hepatic glucose production
Decreases carbohydrate absorption
Reduces LDL cholesterol level and triglycerides
How does metformin work?
Activation of AMP kinase
What are the adverse effects of metformin?
GI disturbances - Diarrhoea - Nausea - Abdominal discomfort - Anorexia Lactic acidosis if improperly prescribed Possible modest weight loss
In whom is metformin contraindicated?
Patients with impaired renal function
What is the drug class of acarbose?
Alpha-glucosidase inhibitors
How does acarbose work?
Doesn’t have to enter bloodstream
Blocks enzymes that digest and promote absorption of starches in small intestine
What are the pharmacokinetics of acarbose?
Not absorbed from GIT
What are the adverse effects of acarbose?
Flatulence/abdominal discomfort
Loose stools and abdominal pain
In whom is acarbose contraindicated?
Patients with
- Inflammatory bowel disease
- Cirrhosis
What are incretins?
Gut hormones release when food is ingested
- GLP-1
- GIP
What do incretins do?
Increase - Insulin release from beta cells - Glucose uptake by muscles Decrease - Glucagon release from alpha cells - Glucose production by liver
What is the drug class of sitagliptin?
“Gliptins”
Dipeptidyl peptidase-4 (DPP-4) inhibitors
What does sitagliptin do?
Increases native GLP-1 levels
How is sitagliptin administered?
Orally
What are the adverse effects of sitagliptin?
URTIs Headaches Hypoglycaemia when combined with insulin Allergic/hypersensitivity reactions Pancreatitis (rare)
What is the drug class of exenatide?
Glucagon-like polypeptide-1 (GLP-1) receptor agonists
How is exenatide administered?
Subcutaneous injection
What are the actions of exenatide?
Potentiate glucose-mediated insulin secretion
Suppress glucagon release
Slow gastric emptying
Loss of appetite
What are the adverse effects of exenatide?
Nausea Vomiting Diarrhoea Weight loss Ab formation Immune reactions Pancreatitis
What is the approach and drug class for managing a relative lack of insulin?
Stimulate pancreas to make more insulin
Sulfonylureas
What is the approach and drug class for managing insulin resistance?
Sensitise body to insulin and/or control hepatic glucose production
Biguanides
What is the approach and drug class for managing glucose absorption?
Slow absorption of starches
Alpha-glucosidase inhibitors
What is the approach and drug class for managing incretins?
Regulate glucagon and insulin
Incretin mimetics and enhancers
What is the approach and drug class for managing glucose reabsorption?
Slow renal glucose reabsorption
SGLT2 inhibitors
