Diabetes Pharm Flashcards
what is the MOA of metformin?
activates AMPK in hepatocyte mitochondria, inhibiting ATP production
blocks gluconeogenesis and subsequent glucose output
also blocks adenylate cyclase so promotes fat oxidation
what is the drug target of metformin
5’-AMPK in hepatocyte mitochondria
and adenylate cyclase
what are the main side effects of metformin?
GI side effects - abdo pain, reduced appetite, diarrhoea, vomiting
why does metformin accumulate in the liver (therapeutic effect) and GI tract (side effect)?
as it is highly polar, requires organic cation transporter-1 to access tissues (present in these places)
when is metformin most effective?
in patients with remaining functional pancreatic islet cells
what is the MOA for dipeptidyl-peptidase 4 inhibitors? (DPP-4)
sitagliptin
inhibits action of DPP-4 in vascular endothelium which normally breaks down incretins in the plasma
therefore limits breakdown of incretins and prolongs their effects
what are incretins?
secreted by enteroendocrine cells, stimulate production of insulin when needed and reduce glucagon.
also slow down digestion and decrease appetite
give examples of incretins?
GLP-1
GIP
what is the drug target for DPP-4 inhibitors? (sitagliptin)
DPP-4 enzyme in vascular endothelium
what are the main side effects of DPP-4 inhibitors?(sitagliptin)
upper respiratory tract infections, flu like symptoms
less commonly - severe allergy
what are the contraindications for DPP-4? (sitagliptin)
pancreatitis
what is the MOA of sulphonylureas? (gliclazide)
inhibits ATP-sensitive K+ channel on pancreatic beta cell
inhibition causes depolarisation of beta cell which stimulates Ca2+ influx
subsequent insulin vesicle exocytosis
aka causes increased release of insulin
what is the drug target for sulphonylureas? (gliclazide)
ATP-sensitive potassium channel on pancreatic beta cells
what are the main side effects of sulphonylureas? (gliclazide)
weight gain
hypoglycaemia
what is the MOA of SGLT2 inhibitors? (dapaglifozin)
reversibly inhibits sodium-glucose cotransporter 2 in PCT
reduces glucose reabsorption and increases urinary glucose excretion
what is the drug target for SGLT2 inhibitors? (dapaglifozin)
sodium-glucose cotransporter 2 in proximal convoluted tubule
what are the main side effects of SGLT2 inhibitors? (dapaglifozin)
urogenital infections slight decrease in bone formation can worsen diabetic ketoacidosis weight loss BP reduction
what are SGLT2 inhibitors dependent on and therefore its contraindications? (dapaglifozin)
renal function
therefore less effective in patients with renal impairment
when should metformin be prescribed in patients with T2DM?
HbA1c above 48mmol/mol even with lifestyle intervention
when is the first intensification of metformin treatment for T2DM?
HbA1c 58mmol/mol despite on metformin
dual therapy with 2 of DPP4i, SGLT2i, gliclazide, pioglitazone
first line treatment for HbA1c over 48 when already given lifestyle advice
Metformin
first line treatment for HbA1c over 58
Metformin
why may you not choose to prescribe sulphonylureas (gliclazide)
can cause weight gain - not for people with already high B,I
hypoglycaemia risk
what patients would you choose to prescribe GLP-1 agonists and SGLT-2 inhibitors to?
patients with CVD risk - prevention
when are thiazolidinediones contraindicated (pioglitazone)
heart failure
what diabetes drug is most tolerable
DPP-4 inhibitors
moderately effective
example of DPP-4 inhibitor
sitagliptin
example of GLP-1 agonist
liraglutide
example of sulphonylurea
gliclazide
example of SGLT-2 inhibitor
empagliflozin
example of thiazolidinedione
pioglitazone
