Lecture 21 - Chemistry of Oral Antidiabetics Flashcards
(39 cards)
What are the classes of oral antidiabetics?
biguanides sulfonylureas glitazone gliptins GLP-1 agonists (not oral)
What are the biguanides?
metformin
buformin
phenformin
Structure of biguanides?
highly charged, highly hydrophilic and very basic
Effect of metformin?
mainly due to the inhibition of hepatic glucose output
What is the presumed site of metformin function?
the liver
Metabolism of metformin?
not metabolised and is unchanged throughout the journey in the body
What is most used to treat T2D?
Metformin
Why were buformin and phenformin withdrawn?
they had toxicity associated and caused acidosis
What is the high basic pKa of biguanides due to?
resonance forms of biguanide stabilising the conjugate acid positive charge so the equilibrium lies to the left
Route of metformin?
orally active so must be active uptake mechanism
1st generation sulfonylureas?
chlopromide
tolbutamide
2nd generation sulfonylureas?
gliquidone
What is the NH attached to sulphur and carbonyl in sulfornylureas?
weakly acidic
Other sulfonylureas?
glibenclamide and glimepiride
gliclazide and glipizide
What are the oldest hypoglycaemia agents?
sulfonylureas
How do sulfonylureas work?
stimulate insulin secretion by binding to sulfonylurea receptor 1 (SUR-1) sub unit of the ATP sensitive K channels in the beta cell plasma membrane
How are sulfonylureas classes?
first and second generation
What are sulfonylureas associated with?
weight gain and hypoglycaemia
Can sulfonylureas be used with metformin?
yes
Meglitinides?
nateglinide
repaglinide
How do meglitinides work?
in a similar manner to sulfonylureas
stimulate insulin secretion by binding to sulfonylurea receptor 1 (SUR-1) sub unit of the ATP sensitive K channels in the beta cell plasma membrane
What do meglitinides have?
weaker binding and dissociation from the SUR-1 binding site of the ATP sensitive K channel
Glitazones?
rosiglitazone
pioglitazone
What do glitazones posses?
the thiazolidinedione moiety
