Pharmacology of diabetes Flashcards
what is the primary mechanism of action of metformin
metformin activates AMPK in hepatocyte mitochondria, this inhibits ATP production which blocks gluconeogenesis and subsequent glucose output
It also blocks adenylate cyclase which promotes fat oxidation. Both help to restore insulin sensitivity.
what is the drug target for metformin
5′-AMP-activated protein kinase (AMPK)
The primary site of metformin action is the hepatocyte mitochondria
what are main side effects of metformin
GI side effects eg abdominal pain, decreased appetite, diarrhoea, vomiting
particularly in high doses, slow dose increase may improve tolerability
what does metformin require to access tissues
it is highly polar and needs ogranic cation transporter-1 (OCT-1)
which is why it can accumulate in the liver and GIT
when is metformin most effective
in the presence of endogenous insulin so is most effective with some residual functioning pancreatic islet cells
give an example of DDP-4 inhibitors
sitagliptin
what does DDP4 stand for
dipeptidyl-peptidase 4
what are the different drugs you can give for diabetes
metformin, DPP4 inhibitors, sulphonylureas, SGLT2 inhibitors
what is the primary mechanism of action of DPP4 inhibitors
work by inhibiting the action of DPP4, which is in vascular endothelium and can metabolise incretins in the plasma
what are incretins
eg GLP-1
are secreted by enteroendocrine cells and help stimulate the production insulin when it is needed eg after eating and reduce the production of glucagon by the liver when it is not needed, they also slow down digestion and decrease appetite
what is the drug target of DPP4 inhibitors
vascular endothelium where the DPP4 enzyme is found
what are the side effects of DPP4 inhibitors
upper RTIs, flu like symptoms eg Upper respiratory tract infections (5% of patients) Flu-like symptoms e.g. headache, runny nose, sore throat
Less common but serious:
Serious allergic reactions/ avoid in patients with pancreatitis
do DPP4 inhibitors cause weight gain
no, unlike other anti diabetic drugs (apart from metformin)
how do DPP4 inhibitor’s mainly act
mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
give an example of a sulphonylurea
gliclazide
what is the primary mechanism of action of sulphonylureas
Inhibit the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell. This channel controls beta cell membrane potential. Inhibition causes depolarisation which stimulates Ca2+ influx and subsequent insulin vesicle exocytosis
what is the target for sulphonylureas
ATP sensitive potassium channel
primary site of SUs inhibitor action is pancreatic beta cell
side effects of sulphonylureas
Weight gain is a likely side effect
Hypoglycaemia (2nd most common)
how do sulphonylureas mainly act
by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
how is weight gain by sulphonylureas mitigated
by the concurrent administration with metformin
what should be considered when prescribing sulphonylureas?
The risk of hypoglycaemia associated with sulfonylureas should be discussed with the patient, especially when concomitant glucose-lowering drugs are prescribed.
give an example of a sodium glucose co-transporter (SGLT2) inhibitor
dapaglifozin
what is SGLT2 inhibitors primary mechanism of action
Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
what is the drug target for SGLT2 inhibitors
SGLT2
The primary site of SGLT2 inhibitor action is the proximal convoluted tubule
