Pharmacology Flashcards
Which transporter transports glutamate?
GLUT2
What does the KATP channel look like?
4 K+ inward rectifiers
4 sulfonylurea receptor subuntis (arrange on the outside)
What closes the KATP channel?
When ATP binds to the kir6.2 subunits
What opens the channel?
When ADP-Mg2+ binds to the SUR1 subunits
Side effects of sulfonylureas?
Hypoglycemia and weight gain
Mg2+ from the SUR1 subunit (thus closing the KATP channel and stimulating insulin release)
Sulfonylureas
bind to SUR1 (at a distinct benzamido site) to close the KATP channel and trigger insulin release
Glinides (Meglitinides)
When and how would you take glinides?
Orally, before a meal
These molecules enhance insulin release from pancreatic beta cells and delay gastric empyting
GLP-1 and GIP
= enhanced glucose uptake and utilization
This molecule decreaes glucagon release from pancreatic alpha cells
GLP-1
= decreased glucose production
Increase insulin secretion
Decrease glucagon secretion
Slow gastric emptying
Decrease appetitie
Incretin analogues e.g. extenatide
Good effects of incretin analogues
Cause modest weight loss
Reduce hepatic fat accumulation
How do you administer incretin analogues?
SC injection twice daily
Side effects of incretin analgoues
Nausea, hypoglycemia, pancreatitis (rare)
Liraglutide
Long acting incretin analogue (suitable for once daily administration)
DPP-4 inhibitors
Gliptins
Do gliptins cause hypoglycemia or weight gain?
No hypoglycemia
Weight neutral
Acarbose
alpha glucosidase inhibitor
How do alpha glucosidase inhibitors work?
Delay absorption of glucose and thus reduce prostprandial rise in blood glucose
Adverse effects of alpha-glucosidase inhibitors
GI effects:
Flatulence, loose stools, diarhorrea, abdominal pain., bloating
Risk of hypoglycemia with acarbose?
No
Biguanide
Metformin
Reduces hepatic gluoconeogenesis
(by stimulating AMP-activated protein kinase (AMPK) )
Reduces carbohydrate absorption
Increase fatty acid oxidation
Metformin
Increase insulin secretion
Sulfonylureas
Glinides
Inhibit DPP4
Gliptins
GLP-1 mimickers
Incretin analogues
Delay absorption of glucose and reduce post-prandial rise in blood glucose
Alpha glucosidase inhibitors
Enhance action of insulin at target tissues
Thiazolidinediones
Selectively block reabsorption of glucose by SGLT2 in proximal tubule
Cause decrease in blood glucose
SGLT2 inhibitors
cause decrease in blood glucose but little risk of hypoglycemia
Adverse effects of metformin
GI side effects Lactic acidosis (rare)
Where would you find PPARy?
Adipocytes
PPARy binds to DNA and promotes expression of genes encoding which proteins
Lipoprotein lipase
Fatty acid transport protein
GLUT 4
Promote fatty acid uptake and storage in adipocytes, rather than skeletal muscle and liver
Reduced hepatic glucose output
Thiazolidinediones
Adverse effects of TZD’s (glitazones)
Weight gain
Fluid retention
Bone fractures
