Antidiabetics (3) Flashcards
What do incretins do?
GI hormones increase in amount of insulin released after eating, but before blood glucose levels are elevated
Incretins inhibit glucagon release from what cells?
a cells of islets of Langerhan
What does glucagon do?
incease blood glucose levels
What are the 2 main incretins?
GLP-1
GIP
What inactivates GLP-1 and GIP?
DPP-4
Where is GLP-1 secreted from?
L cells in jejunum and ileum
long term effects of GLP-1 in animals
increas B cell mass
maintain B cell function
GIP and GLP-1 in T2D
defective
MOA GLP-1
- promote release of insulin
- lower glucagon levels
- promote satiety (slow gastric emptying)
GLP-1 drugs
Byetta (exenatide)
Bydureon
Victoza (liraglutide)
Bydureon
encapsulated form of Byetta
slow release
What drug is also used in nondiabetics for obesity?
liraglutide (Victoza)
What is GIP also known as?
glucose dependent insulinotropic peptide
GIP drugs
still in research
not on market yet
GIP MOA
thought to induce insulin secretion
DPP4 acts as a ____ protein involved in important pysiological processes
multifunctional
DP4 is also known as
CD26
adenosine-deaminase binding protein (ADAbp)
DPP4 cleaves off _____ which is a specific ____
dipeptide HisAla
antagonist
Gliptans are what type of drug?
DPP4 inhibitor
DPP-4 has a strong influence on ____ and ____
insulin sensitivity
glucose homeostasis
What is poised to be next major drug class for treatment of T2D?
DPP4 inhibitors
Active site of DPP4 inhibitor
within large cavity at interface of b-propeller and hydrolase domain
**wide structural variety
What other two DPP share identical active stie with DPP4?
8 and 9
DDP4 inhibitors must possess a potency and PK profile that produces _____% inhibition for ____ hours
>90%
24 hours
DPP4 inhibitors must develop what?
selectivity against DPP8 and 9
What drugs are gliptans?
sitagliptin
vidaglipitin
saxagliptin
alogliptin
linagliptin
T/F januvia can cause your blood glucose to go too low
false. does not work when blood glucose is low
Is byetta or januvia indicated as an earlier treatment?
januvia
side effects of GLP-1 and DPP4 inhibitors
increased risk of pancreatitis
a-glucosidase inhibitor MOA
delay of digestion of carbs
decrease postprandial blood glocuose and insulin
**delay absorption
Metabolism of a-glucosidase inhibitors
O methylated
O sulfated
O glucuronate
(SAR) a-glucosidase inhibitors have inhibition of what?
kinetics of a-glucosidase complex
(SAR) cleavage of a-glucosidase inhibitors occurs how?
energy oxonium ion
(SAR) a-glucosidase inhibitors require what groups that appear glucose like?
NH2 and OH groups
(SAR) a-glucosidase inhibitors possess what?
protonate amines that occupy position of oxonium
