Diabetes Pharmacology Flashcards
What are the drugs for diabetes? (4)
Metformin
Sitagliptin
Gliclazide
Dapaglifozin
What is the drug class of metformin?
metformin
What is the drug target for metformin?
5′-AMP-activated protein kinase (AMPK)
The primary site of metformin action is the hepatocyte mitochondria
What is the primary method of action of metformin?
Primary effect – it activates AMPK in hepatocyte mitochondria
- This inhibits ATP production
- This blocks gluconeogenesis and subsequent glucose output
It also blocks adenylate cyclase which promotes fat oxidation. Both help to restore insulin sensitivity.
What are the main side effects of metformin?
GI side effects (20-30% of patients)
e.g. Abdominal pain, decreased appetite, diarrhoea, vomiting)
Particularly evident when very high doses are given. A slow increase in dose may improve tolerability.
What does metformin require to access tissues?
Metformin is highly polar and requires organic cation transporter-1 (OCT-1) to access tissues. This explains why it can accumulate in the liver (therapeutic effect) and gastrointestinal tract (side effects)
When is metformin most efective?
Metformin is most effective in the presence of endogenous insulin so is most effective with some residual functioning pancreatic islet cells
What drug class is sitagliptin?
Dipeptidyl-peptidase 4 (DPP-4) inhibitors
What is the drug target of siptiglabin?
DPP-4 (Dipeptidyl peptidase 4 (DPP-4))
The primary site of DPP-4 inhibitor action is the vascular endothelium
What is the primary mechanism of action of siptiglabin?
Primary effect - Work by inhibiting the action of DPP-4. This enzyme is present in vascular endothelium and can metabolise incretins in the plasma.
Incretins (e.g. GLP-1) are secreted by enteroendocrine cells and help stimulate the production of insulin when it is needed (e.g. after eating) and reduce the production of glucagon by the liver when it is not needed (e.g. during digestion). Incretins also slow down digestion and decrease appetite.
What are side effects of sitagliptin?
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
Compared to other anti-diabetic drugs (although not metformin) what do sitagliptin not do?
cause weight gain
How do DDP-4 inhibitors act mainly by?
DPP-4 I’s act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present.
What drug class is gliclazide?
sulphonylurea
What is the drug target for sulphonylurea?
ATP-sensitive potassium channel
The primary site of SUs inhibitor action is the pancreatic beta cell
What is the primary mechanism of action for sulphonylureas?
Primary effect – 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 are likely side effects of sulphonylurea?
weight gain is a likely side effect
hypoglycaemia (2nd most common)
How do sulphonylureas mainly act?
The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present
Weight gain from sulphonylureas are mitigated by what else?
by the concurrent administration with metformin
What drug class is dapaglifozin?
Sodium-glucose co-transporter (SGLT2) inhibitors
What is the drug target for Sodium-glucose co-transporter (SGLT2) inhibitors?
SGLT2
The primary site of SGLT2 inhibitor action is the proximal convoluted tubule
What is the primary mechanism of action for sodium-glucose co-transporter (SGLT2) inhibitors?
Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
What are side effects of SGLT2 inhibitors?
Uro-genital infections due to increased glucose load (5% of patients)
Slight decrease in bone formation
Can worsen diabetic ketoacidosis (stop immediately)
What “benefits” do SGLT2 inhibitors cause?
weight loss and reduction in BP
