Diabetes Management Flashcards
Sulphonylureas: mechanism of action?
Stimulates endogenous insulin secretion (from pancreatic B cells);
Act by binding K-ATP channels and reducing K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.
What are the sulphonylureas?
- Gliclazide
- Glipizide
- Glibenclamide
- Glimepiride
- Chlorpropramide
What are the adverse effects of sulphonylureas?
- Hypoglycemia
- Weight gain (avoid in the obese)
- Renal excretion: do not give to those with renal impairment
What are the contraindications for sulphonylureas?
- Renal impairment (renal excretion)
- Pregnancy (crosses placenta)
- Type I DM
- Overweight people
What is the mechanism of action of the meglitinides?
Insulin secretagogues; secrete insulin rapidly and for short duration.
Bind K-ATP channels –> decrease K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.
what are the meglitinides?
Repaglinide
Nateglinide
Which drugs have the same adverse effects as the meglitinides?
Sulphonylures; include hypoglycaemia and weight gain.
Meglitinides pharmacokinetics.
Rapid onset offset: T1/2 = 3h.
Administer pre-meal to anticipate post prandial rise in glucose
What is biguanide?
Metformin
Biguanides mechanism of action.
Sensitisation to insulin/decrease hepatic glucose production.
- Activate AMP-kinase
- Increase insulin mediated peripheral glucose uptake (via GLUT4)
- Increase hepatic insulin sensitivity and decrease hepatic glucose production
- small decrease in LDL and TGs.
What are the thiazoglitazones?
e.g. pioglitazone
What is the MoA of pioglitazone?
Like metformin: potentiate the action of endogenous or injected insulin.
- Interact with PPARa on adipose tissue;
- Alters transcription of genes involved in insulin signalling e.g. GLUT4
- Increase FFA uptake
- Improves HDL cholesterol and plasma TGs
- Activates AMP
Adverse effects of glitazones?
MANY!!
- Weight gain
- Oedema / fluid retention / CCF
- HA, fatigue, GI upset
- Bone fractures
-NO Hypoglycemia
Adverse effects of biguanides?
- No weight gain/?LoW
- No change to insulin secretion
- no hypoglycemia
- GI disturbances
- Lactic acidosis if improperly prescribed (in patients with hepatic or renal disease)
What are the alpha glucosidase inhibitors?
Acarbose
What is the MoA of acarbose?
Block gut a-glucosidase; enzyme that digests and absorbs starches.
AEx of acarbose?
- Flatulence/GI upset
- Loose stools
CI: IBD or cirrhosis
CIx biguanides?
Renal failure: risk of lactic acidosis.