Oral Hypoglycaemic Agents Flashcards
Chronic disturbed carbohydrate and lipid metabolism results from
absolute and relative lack of insulin
What is meant by ‘relative’ lack of insulin?
Insulin is present but doesn’t work as effectively (resistance)
T/F Insulin levels are always abnormal in T2D
False; early stages insulin levels can be normal or slightly elevated; they fall as the disease progresses
Early in T2D, insulin levels are __________ or _________; as the disease progresses, insulin levels __________ and can resemble T1D
normal, slightly elevated; decrease
What causes insulin resistance?
decreased numbers and/or impaired function of insulin receptors
Pharmacotherapy in T2D needs to target
impaired secretion of insulin and receptor responsiveness (dysfunctional)
How do sulphonylureas (oral hypoglycaemics) stimulate insulin release?
Inhibit ATP-sensitive K+ channel (normally hyperpolarizes B cell, powered by ATP from glucose metabolism in mitochondria) causing depolarization and Ca2+ influx that triggers exocytotic release of insulin
Sulfonylureas
chlorpropramide, glibenclamide, glipizide
What is the action of sulfonylureas?
Increase in insulin secretion from B cells by inhibiting Katp channels - restores phase 1 insulin secretion
What are the adverse effects of sulfonylureas?
hypoglycaemia and weight gain; cross BBB so can’t be used in pregnancy; nephropathy needs to be monitored bc excreted by kidney
What type of receptor is the insulin cell surface receptor?
Tyrosine kinase
What is the action of the insulin receptor?
Insulin binds the tyrosine kinase receptor that switch on protein and glycogen synthesis, glucose transport, and translocation of the GLUT4 transporter to cell surfaces to take up glucose for metabolic pathways
Metformin is what class of drug?
Biguanide
What are the actions of metformin for tx in T2D?
increase insulin-mediated peripheral glucose uptake; reduce hepatic glucose production; decrease carbohydrate absorption; reduce LDL and TAG levels
What is the mechanism of metformin?
Activation of AMP kinase
What are the adverse effects of metformin?
GI disturbances: diarrhoea, nausea, abdominal discomfort, anorexia; lactic acidosis; weight loss; contraindicated in impaired renal function
In treatment of T2D, sulfonylureas target
insulin secretion - stimulate secretion from pancreas to restore phase 1 insulin spike
In treatment of T2D, biguanides (metformin) target
insulin resistance - sensitize the body to insulin and/or control hepatic glucose production
Acarbose
alpha-glucosidase inhibitors
What is the mechanism of alpha-glucosidase inhibitors?
block the enzymes that digest and promote absorption of starches in the SI
What are the adverse effects of alpha-glucosidase inhibitors?
flatulence, abdo discomfort, loose stools, abdo pain, contraindicated in IBD or cirrhosis
In tx of T2D, alpha-glucosidase inhibitors target
glucose absorption
Incretins target
insulin secretion and glucagon secretion
Incretins __________ insulin and _________ glucagon
increase; decrease
Dipeptidyl peptidase-4 inhibitors target
DPP4 which breaks down GLP-1
What is the action of DPP4 inibitors?
Increase GLP-1 levels which increase insulin and decrease glucagon
Sitagliptin
DPP4 inhibitor
What are the adverse effects of DPP4 inhibitors?
URT infections; headaches; hypoglycaemia in combo with insulin; allergic/hypersensitivity reactions; pancreatitis
Exenatide
GLP-1 receptor agonist
How is exenatide administered?
subcutaneous injection
What are the actions of exenatide?
potentiate glucose-mediated insulin secretion (GLP-1 action); suppress glucagon release; slow gastric emptying; decrease appetite
What are the adverse effects of exenatide (GLP-1R agonist)?
Nausea, vomiting, diarrhoea; weight loss; Ab formation, immune reactions, pancreatitis; endocrine neoplasias
In the tx of T2D, incretins, incretin mimetics and enhancers target
incretins - GLP-1, GIP; increase insulin and decrease glucagon
In the tx of T2D, SGLT2 inhibitors target
sodium glucose cotransporter 2 to slow renal glucose reabsorption
What is the treatment progression in T2D?
diagnosis; therapeutic lifestyle change; monotherapy (metformin); combo therapy - oral only (until renal effects; also SC exenatide soon); combo therapy - oral with insulin
Target glucose homeostasis in diabetes treatment are
4-8mmol/L
Target HbA1c levels in diabetes treatment are
6%
