Diabetes Pharmacology Flashcards
List drug classes that increase secretion of insulin through insulin-independent action
Sulphonylureas
Incretin analogues
DPP-4 inhibitors
List drug classes that decrease insulin resistance and reduced hepatic glucose output through insulin-dependent action
Biguanides
Thiazolidinediones (TZD’s)
List a drug class that slows glucose absorption from the GI tract through insulin-independent action
Alpha-glucosidase inhibitors
List a drug class that blocks reabsorption of glucose in the kidneys through insulin-independent action
SGLT2 inhibitors
Through which transporter does glucose enter the beta-cell in the pancreas?
GLUT2
What effect does ATP in the beta-cell of the pancreas have on K channels?
Closes them, causing depolarisation of the membrane
How is insulin released following depolarisation of the membrane of the beta-cell?
Depolarisation causes opening of Ca channels, causing insulin-containing vesicles to exocytose
List the components of the Katp channel
4x Kir6.2 units
4x SUR1 units
Which part of the Katp channel does ATP bind to?
Kir6.2 unit
What binds to the SUR1 part of the Katp channel? What does this cause?
ADP-Mg
Repolarisation to inhibit insulin secretion
How do sulphonylurea drugs work?
Displace ADP-Mg from SUR1 on Katp channel to cause depolarisation to promote insulin release
The effect of sulphonylurea drugs is independent of glucose conc. True/False?
True
Give examples of sulphonylureas
Tolbutamide
Glibenclamide
Glipizide
What is the main difference between tolbutamide and glibenclamide?
Glibenclamide is more potent and longer acting
Only need to take glibenclamide 1x/day
Can sulphonylureas cause hypoglycaemia?
Yes
Greater risk with long-acting agents
How do glinides differ from sulphonylureas?
Bind to specific part of SUR1
Rapid action - less likely to cause hypoglycaemia
Incretin hormones stimulate production of insulin. What are the two main endogenous incretin hormones?
GLP-1
GIP
GLP-1 and GIP enhance insulin production. What effect does GLP-1 have on glucagon?
Decreases glucagon release from alpha-cells
Give an example of an incretin analogue
Extenatide
Which enzyme rapidly inhibits the action of incretin hormones?
DPP-4
How do DPP-4 antagonists (gliptins) work?
Inhibit DPP-4 to prolong actions of GLP-1 and GIP
Give an example of a DPP-4 inhibitor
Sitagliptin
What is the function of alpha-glucosidase in the intestine?
Breaks down carbohydrate into absorbable glucose
How do alpha-glucosidase inhibitors work?
Inhibit alpha-glucosidase to delay absorption of glucose, thus reducing post-prandial increase in blood glucose
Give an example of an alpha-glucosidase inhibitor
Acarbose
Acarbose has great risk of hypoglycaemia. True/False?
False
No risk whatsoever
What is the 1st line therapy for type 2 diabetes?
Biguanides (metformin)
What is the proposed action of metformin?
Reduces hepatic gluconeogenesis by stimulating AMPK
Enhances glucose uptake by muscle
Does metformin cause hypoglycaemia?
No
Metformin causes weight gain. True/False?
False
Weight loss
List a significant adverse effect of metformin
Lactic acidosis (as a result of less gluconeogenesis)
How do TZDs work?
Agonist of PPAR-alpha which associated with RXR to enhance transcription of genes encoding insulin signalling
(ultimately enhancing insulin action at tissues)
Which transporter moves glucose into skeletal muscle?
GLUT4
TZDs can cause weight gain. True/False?
True
How do SGLT2 inhibitors work?
Block reabsorption of glucose in convoluted tube of nephron to cause glycosuria
Name a SGLT2 inhibitor
Dapagliflozin
What is the main adverse effect/risk of SGLT2 inhibitors?
Increased risk of UTI
Thrush
Give an example of a TZD
Pioglitazone
