Pharmacology Flashcards
What are the five main actions of insulin?
- induces glucose uptake & utilisation
- lowers blood glucose
- promotes formation of glycogen (storage)
- promotes conversion of glucose into fat in adipose
- stimulates amino avid uptake & protein formation
Name four drugs classes that act to reduce insulin secretion
- sulfonylureas
- incretin analogues
- DDP-4 Inhibitors
Name two drug classes that decrease insulin resistance
- biguanides
- thiazolidinediones
What two drug classes are independent on insulin?
alpha glucosidase inhibitor (slow absorption) & SGLT2 inhibitors (enhance excretion)
Describe the action of sulfonylureas
Promote insulin secretion by acting on KATP channels in beta cells. By binding to the SUR1 unit they close the channel leading to depolarisation and vesicle release.
Name examples of sufonylureas
- gliclazide/tolbutamide
- glipizide
What are the side effects of sulfonylureas?
Hypoglycaemia & weight gain
When are sulfonylureas contraindicated?
Renal impairment, elderly, pregnancy
Describe the physiology of incretins
- Ingestion of food stimulates glucagon like peptide (GLP1) and Glucose dependent insulinotropic peptide (GIP) from enteroendocrine cells in the small intestine.
- GIP and GLP1 enter the portal blood
- As a result they enhance insulin release from beta cells to increase glucose uptake & decrease glucagon release from alpha cells to decrease glucose productions
What enzyme inhibits incretins?
DDP-4
Name two incretin analogues
extenatide & liraglutide
How are incretin analogues administered?
subcutaneously
Name examples of DDP-4 inhibitors
silagliptin, saxaglipin, vildagliptin
What do alpha glucosidase inhibitors do?
Inhibit alpha glucosidase the brush border enzyme that breaks down carbs to absorbable glucose. Inhibitors act to prevent/delay glucose absorption
Are alpha glucosidase inhibitors commonly used in the UK?
No
What drug is a biguanide?
Meformin
What does metformin act to do?
- decrease hepatic gluconeogenesis
- decrease carbohydrate absorption
- increase glucose uptake & utilisation
- increase fatty acid oxidation
What are the side effects of metformin?
GI disturbance/lactic acidosis
Clinically what is metformin useful for?
reducing microvascular complications, preventing hypoglycaemia, helps with weight loss
Name an example of a thiazolidinediones
pioglitazone
How do thiazolidinediones work?
Enhance insulin action at target tissues but acting as an exogenous agonist of nuclear receptors that act as transcription factors for proteins involved in insulin signalling & lipid metabolism
What are the side effects of thiazolidinediones?
weight gain, fluid retention, hepatotoxicity & bone fractures
How do sodium glucose cotransporter 2 inhibitors work?
Act selectively to block the reabsorption of glucose by SGLT2 in the proximal tubule causing glycosuria
Name an example of an SGLT 2 inhibitor
Empagliflozin
