Diabetes drugs Flashcards
What is the first line management for type 2 diabetes?
Metformin
What class of drugs in metformin?
Biguanide
Mechanism of action of metformin
Reduces hepatic gluconeogenesis by stimulating AMPK
Increase glucose uptake by skeletal muscle
Reduces carboydrate reabsorption
Increases fatty acid oxidation
Side effects of metformin
GI upset (start low go slow)
Rarely lactic acidosis
Liver failure
Rash
What is the second line management in type 2 diabetes?
Suplhonylureas
Example of sulphonylurea
Tolbutamide
Glipizide
Glibendamide
What is the mechanism of action of sulphonylureas?
Displace ADP-Mg2+ from the SUR1
Thus closing the Katp channel and stimulating insulin release
Side effects of suplhonylureas
Hypo
Weight gain
Who is at most risk of hypo with sulphonylureas?
Longer acting agents
Elderly
Reduced hepatic/renal function
What can suplhonylureas be used in conjunction with?
Metformin or TZDs
Example of glinides
Repaglinide
Nateglinide
How do glinides work?
Bind to SUR1 to close Katp channel & stimulate insulin release
Which are glinides less likely then sulphonylureas to cause hypo?
Rapid onset
Example of incretin analogue?
Extenatide
Mechanism of action of incretin analogues
Mimic action og GLP-1 but are longer lasting
Bind to GPCR GLP-1 that increase intracellular cAMP
Causes increase insulin, decreased glucagon, decreased gastric emptying, decreased appetite
Pros of incretin analogues
Weight loss
Reduced heaptic fat accumulation
How are incretin analogues adinisered?
2x daily SC injection
Side effects of incretin analogues
Nausea
Hypo
Pancreatitis
Example of DPPA inhibitor
Sitagliptin
Mechanism of action of DPP4 inhibitors
Rapily terminates actions og GIP + GLP
Mechanism of action of TZDs
Enhance action og glucose at target site (reduce amount needed to maintain BG)
PPARy-RXR complex binds to DNA to repress genes
Promotes fatty acid uptake and storage in adipocytes rather than skeletal muscle & liver
Side effect of TZDs?
Weight gain
Fluid retention (don’t use in HF)
Hepatotoxicity
Increased bone fractures (don’t use in osteoperosis)
Mechanism of action of SGLT2 inhibitors
Selectively block reabsorption of glucose in kidneys to deliberately cause glucosuria
Example of SGLT2 inhibitor
Dapaglifozin
Side effects of SGLT2 inhibitors
Thrush
UTI
What is a-glucosidase?
Brush border enzyme that breaks down starch + dissacharides to absorbable glucose
Mechanism of action of a-glucosidase inhibitors?
Delay absorption of glucose thus reducing postpradndial increase in BG
Side effect of a-glucosidase inhibitors
GI - flatulence, loos stools, bloating
Example of a-glucosidase inhibitor
Acarbose
