Diabetes Medication - Metformin, Sulphonylureas, TZDs, Incretins, SGLT2 Inhibitors Flashcards
What is the molecular mechanism of metformin?
Inhibits complex 1 of the mitochondrial respiratory chain resulting in a fall in intracellular ATP
What are the physiological mechanisms of metformin?
Lowers hepatic glucose production
Increases gut glucose utilisation and metabolism
What are the sites of action of metformin?
Intestines, Liver, Kidneys.
This is because the metformin molecules are largely hydrophilic therefore require active transport to enter the cells via the Organic Cation Transporter. These OCT are present in the above locations.
What are the side effects of metformin?
Gastrointestinal Intolerance - to reduce the effects start the medication slowly
Metformin Associated Lactic Acidosis- this is because metformin increases lactate production; associated with kidney problems
What is the molecular mechanism of sulphyonylureas?
Inhibit ATP-dependent K+ channels in pancreatic beta cells. This increases membrane potential and Ca2+ influx leading to subsequent insulin release.
What is the physiological mechanism of sulphonylureas?
Stimulate pancreatic insulin secretion
Name some sulphonylureas…
GLICLAZIDE
What are the side effects of sulphonylureas?
Hypoglycaemia
Weight gain - insulin increases appetite
Cardiovascular Risk
What is the molecular mechanism of Thiazolidinediones?
They are PPAR gamma ligands which result in the switching on of hundreds of genes
What is the physiological mechanism of Thiazolidinediones?
The main effect is on adipocytes.
They increase differentiation from pre-adipocytes to adipocytes which increases subcutaneous fat mass. This fat is drawn put of the liver and muscle which reduces lipotoxicity adn increses insulin secretion
Name a TZD…
Pioglitazone
What are the side effects of TZDs?
Weight Gain, Fluid Retention, Fracture Risk
What drug type is the only true insulin sensitiser?
TZDs
What are the two types of incretin drugs?
DPP4 Inhibitors
GLP-1 Receptor Antagonist
What is the mechanism of DDP4i?
Inhibit the breakdown of the incretins, GLP-1 and GIP. This promotes insulin secretion.
Name examples of DDP4i?
Sitaglipin, Linaglipin, Saxaglipin
What are the side effects of DDP4i?
Generally minimal
Hypoglycaemia
Pancreatitis
What is the mechanism of GLP-1 RA?
Promote insulin secretion in a glucose dependent mechanism. They also act on the hypothalamus to reduce appetite and on the intestine to reduce gastric emptying
What are examples of GLP-1 RA?
Liraglutide, Semaglutide
What are side effects of GLP-1 RA?
Nausea
Vomiting
Gallstones
Pancreatitis
What is the molecular mechanism of SGLT2 Inhibitors?
They inhibit the SGLT2 Transporter in the kidney. This prevents glucose resorption in the kidney and hence leads to glucose excretion via the urine.
What are the other impacts of SGLT2 Inhibitors?
Renal Protection
CVD Benefit
Increase Ketone Body Production
Name some SGLT2 Inhibitors…
Empagliflozin
Dapagliflozin
Canagliflozin
What are some side effects of SGLT 2 Inhibitors?
Thrush Fournier Gangrene Hypovoleamia Hypotension Diabetic Ketoacidosis
