Drugs for T2DM Flashcards
what type 2 diabetes drugs are dependent upon insulin
increasing secretion of inulin
- sulfonylureas
- incretin
- glinides
- Gliptins (DPP4-inhibitors)
decreasing insulin resistance and reducing hepatic glucose output
- biguanides
- thiazolidinediones (glitazones)
what type 2 diabetes drugs are independent from insulin
slowing glucose absorption from the GI tract
-glucosidase inhibitors
enhancing glucose excretion by the kidneys
-sodium glucose type-2 inhibitors (SGLT2)
how does high plasma glucose lead to insulin secretion
high blood glucose leads to increased disunion of glutamate into the B cell by GLUT2
then glucose is phosphorylated by glucokinase
glycolysis of glucose-6-phosphate in mitochondria yields ATP
increased ATP/ADP ratio within cell closes ATP k+ channels causing membrane depolarisation
opening of voltage-activated Ca2+ channels allowing Ca++ in triggers insulin secretion
how does ATP cause the closing of the ATPk channel
high glucose means the ATP levels are high causing the closing of the K channel by ATP binging to a Kir6.2 unit in the channel leading to depolarisation and insulin release
how does low ATP open the Katp channel
low glucose means there are low ATP levels (less glycolysis) so ADP levels are high
ADP binds to the SUR1 subunit which opens the channel to maintain the resting action potential of the B cell abnd preventing insulin release
what do sulfonylureas do
bing to SUR1 and CLOSE the channel causing depolarisation and insulin release independent of plasma glucose concentration
what do sulfonyureas cause
pancreatic B cell insulin secretion - require a functional mass of B cells to be effective
how do sulfonyureas act
by displacing the ADP bound to the SUR1 unit and binding instead to close the K atp channel and stimulate insulin release
what is an important side effect of sulfonyureas
may cause hypoglycaemia by excessive insulin secretion as they are causing insulin secretion without any input from glucose levels
who is at greater risk of hypoglycaemia from sulfonyureas
the elderly
patients with reduce hepatic/renal function (particularly CKD)
those on long acting agents
when are sulfonyureas first line treatment
for patients intolerant to metformin or with weight loss
when are sulfonyureas second line
when used in conjunction with metformin
what affect do sulfonyureas have on weight
cause weight gain
when should you avoid long duration agents (sulfonyureas)
in people with CKD
elderly
pregnancy
breast feeding
How do glinides work
similar to sulfonylureas
action is augmented by glycaemia
promote insulin secretion in response to meals
bind to SUR1 to close Katp channels and trigger insulin release
less likely to cause hypoglycaemia