DM Hypoglycemics Flashcards
(34 cards)
What are Insulin Sensitizers
Biguanides
Thiazolidinediones
Name a Biguanide
Metformin
MOA of Metformin
Lower hepatic glucose production
Raise density of insulin receptors at tissues
Lower intestinal glucose absorption
Improve muscular glucose absorption
Uses of Metformin
Does not affect insulin secretion
Take with meals or after meals to lower GI ADR
ADR of Metformin
GI issues - diarrhoea, vomiting, indigestion.
Raise risk of Vit B12 malabsorption and hence Vit B12 deficiency and can worsen symptoms of neuropathy
Use with caution in patients with renal problems
Names of Thiazolidinediones
Pioglitazone
Rosiglitazone
MOA of Thiazolidinediones
Raise insulin-dependent glucose disposal and lower insulin resistance in periphery and liver
Exact mechanism unclear.
Primary MOA is to activate nuclear transcription factor PPAR-gamma.
PPAR ligands regulate glucose metabolism, adipogenesis, improve insulin sensitivity at adipose tissues, liver and skeletal muscles.
Stimulation of receptors can raise production of GLUT 1 and GLUT 4, enhancing tissue sensitivity to insulin.
Uses of Thiazolidinediones
High glucose-lowering efficacy
Does not affect insulin secretion
ADR of Thiazolidinediones
Weight gain, peripheral edema, higher risk of HF (fluid retention) and bone fractures
Pioglitazone induce CYP450 activity and reduce serum concentrations of CYP450 metabolized drugs
What are examples of Insulin Secretagogues
Sulfonylurea
Meglitinides
MOA of Sulfonylurea
Stimulate insulin release from beta cells in pancreatic islets
Target b-cell ATP-sensitive K channel, which plays major role in controlling b-cell membrane potential
Bind to SU receptor proteins, subunits of K-ATP channels.
Drug binding inhibits K-ATP channel mediated K+ efflux, triggering Ca-dependent exocytosis of insulin granules from pancreatic b-cells
Efficacy of Sulfonylurea
Take 0.5h before food for better absorption
ADR of Sulfonylurea
Can cause weight gain (1-4kg) due to lipogenic effect of insulin
Risk for hypoglycaemia, highest in Glibenclamide. Especially in elderly and renal or hepatic impairment
Contraindicated for Sulfa Allergy
Names of Sulfonyurea
Glipizide
Glicazide
Glibenclamide
Glimepiride
Names of Meglitinides
Nateglinide
Repaglinide
MOA of Meglitinides
Bind and close ATP-dependent K channels on pancreatic beta cells in glucose-dependent manner stimulating insulin release.
This is mediated through unique binding site on SUR1 of beta cell that differs from sulfonylureas’ site of action.
Efficacy of Meglitinides
Taken before meals to control post-prandial glucose levels - due to rapid onset and short DOA
ADR of Meglitinides
Use with caution in hepatic impairment patients.
Example of a a-Glucosidase inhibitors
Acarbose
MOA of acarbose
a-glucosidase hydrolyzes oligosaccharides to glucose and other sugars
Reversibly inhibit membrane-bound a-glucosidase in intestinal brush borders, slowing down rise in glucose levels after a meal.
ADR of acarbose
Higher glucose load in colon causes gaseous distension and flatulence
Stomachache, occasional diarrhoea, belching
Banned for patients with GI issues such as IBD, severe renal or hepatic disease.
Examples of Incretin-based therapy drugs
Dipeptidyl Peptidase 4 Inhibitors
Glucagon-like Peptide-1 Receptor Agonist
Names of DPP-4 inhibitors
Sitagliptin
Vildagliptin
Linagliptin
MOA of DPP-4 inhibitors
DPP-4 is an enzyme that degrades the incretin hormones (stimulated with meals) GLP-1 and GIP.
DPP-4 inhibitors prolong action of endogenous incretins
This stimulates pancreatic B-cells to raise glucose-stimulated insulin release
Suppress a-cell mediated glucagon release and hepatic glucose production.
