pharmacology diabetes Flashcards
What do people with T2D usually present with?
Hyerglycaemia, raised HbA1c, hypertension, dyslipidaemia
What is their therapeutic objective for someone with T2D?
Decrease HbA1C, reduce hypertension, weight loss, help dyslipidaemia
Are lifestyle changes effective for T2?
If they adhere to them they are as effective as medications
What do you usually prescribe first and afterwards for T2D?
First prescribe lifestyle intervention and after that metformin if needed
What ahppens if HbA1C rises to 48mmol/l on lifestyle intervention?
Prescribe metfomin (oral 500mg/day)
What is standard dose of metformin?
500mg/day oral
What happens if on metformin, they have an intensificiation that rises HbA1C to 58?
Consider dual therapy (eg with DPP4 inhibitor
What happens if second intesification ?
consider triple therapy
What is the molecular structure of metformin?
Metformin is polar and water soluble and therefore needs organic cation transporter 1 in order to be transported across bilayer
Where is OCT-1 (organic cation tranpsorter) present and why?
OCT-1 is expressed in hepatocytes (for therapeutic effect), small intestine enterocytes (for absorption), kidney (for excretion)
Why monitor kidney function when on metformin?
because it can put them at risk of lactic acidosis as inhibits first step of gluconeogenesis leading to accumulation of lactic acid.
eGFR cut off for metformin?
eGFR <30 is cut off (metformin cannot be used due to risk of lactic acidosis)
What are side effects of metformin? What should you recommend?
GI symptoms. Tell them to after food or switch to better preparation (eg sustained release metformin)
What is the mechanism of metformin?
It activates AMPK in hepatocyte mitochondria inhibiting ATP production and thus inhibiting gluconeogenesis (decreases HGO). It also blocks adenylyl cyclase which promotes fat oxidation. Both increase insulin sensitivity.
What is the drug target of metformin?
AMPK in hepatocyte mitochondria
What are side effects of metformin? What can help with this?
GI symptoms - abdominal pain, diarrhoea, nausea, vomiting. (usually at higher doses). Slowly increasing the dose can help with these symptoms. Also take after food and maybe use sustained release metformin instead.
When is metformin most effective?
Most effective in presence of endogenous insulin
What is the structure of metformin and its implications?
Highly polar (water soluble) and needs OCP-1 transporter for transport. This transporter expressed in hepatocytes (therapeutic effect), enterocytes (GI side effects) and kidney (excretion)
What is DPP-4 inhibitor example?
sitagliptin
What is the mechanism of action of DPP-4 inhibitors?
DPP-4 is involved in the metabolism of incretins like GLP-1 (which increase insulin production and satiety). Therefore DPP4 inhibitors inhibit DPP4 and increase incretins.
Where is the site of action of DDP-4 inhibitors?
vascular endothelium
What are side effects of DPP4 inhibitors?
upper respiratory tract infections (flu-like symptoms)
when should DPP4 inhibitors not be used?
pancreatits
do DPP4 inhibitors cause weight gain?
no
when are DPP4 inhibitors most effective?
residual β-cell function (insulin present)
What is an example of a sulphonylurea?
gliclazide
What is the mechanism of sulphonylurea?
Inhibits ATP sensitive potassium channels on pancreatic β cells, causing depolarisation, calcium influx and therefore exocytosis of insulin / insulin production.
What is the site of action of sulphonylurea?
ATP sensitive potassium channels on pancreatic β cells
What is side effect of sulphonylurea?
Weight gain & hypoglycaemia
when is sulphonylurea drugs most effective?
residual β function (insulin present)
how can weight gain caused by sulphonylurea be mitigated?
concurrent use with metformin
What is example of SGLT2 inhibitor?
dapaglifozin
What is the mechanism of SGLT2 inhibitor?
Binds on SGLT2 on PCT in kidney in order to inhibit sodium/glucose transporter, prevent glucose reabsopriton and increase glucose excretion in urine
What is the site of action of SGLT2 inhibitors?
SLT2 on PCT in kidney
What are the side effects of SGLT2 inhibitors?
Uro-genital infections due to increased glycosuria, slight decrease in bone formation and can worsen diabetic ketoacidosis
What are extra benefits of SLT2 inhibitors?
weight loss and decrease in BP
when is SGL2 inhibitor less effective and why?
depends on renal function so less effective in those with renal impairement
