Pharmacology of Diabetes Flashcards
What is the pathophysiology of type 1 diabetes?
Beta cell destruction by autoantibodies, insulin deficient
Pathophysiology of type 2 diabetes
Balance between insulin resistance and insulin deficiency
Name the 3 origins of insulin in terms of pharmacological use
1) Animal - porcine, bovine
2) Human
3) Analogue - genetically altered human insulin
What class of drug is Metformin?
Biguanide
What action does metformin have on hepatic AMPK?
Phosphorylates/activates it
What two actions does metformin have on the liver?
Decreases gluconeogenesis and glycogenolysis
What effect does metformin have on muscles?
Improves glucose uptake by increasing cell-surface expression and activity of insulin receptors
What is one of the major benefits of metformin that puts it above other oral hypoglycaemic drugs?
Extremely low risk of hypoglycaemia
When should metformin be avoided and why?
When glomerular filtration rate is low because it can cause lactate accumulation
What class of drugs are insulin secretagogues and what does this mean?
Sulfonylureas e.g. gliclazide. They increase the amount of insulin released in response to a rise in plasma glucose
Name an example of a thiazolidinedione
Pioglitazone
Rosiglitazone
What is the mode of action of thiazolidinediones and what gene are they agonists to?
PPAR gamma agonists.
Insulin ‘sensitiser’
What is a unique downside of using thiazolidinediones?
Increased risk of bladder cancer
What do Dipeptidyl Peptidase-4 (DPP-4) inhibitors end in
‘gliptin’
e.g. sitagliptin
What class of drug is Linagliptin?
DPP-4 inhibitor
What is the normal mode of action of DPP-4
Inactivates incretin hormones GLP-1 and GIP
What intestinal cells does GLP-1 come from?
Intestinal L-cells
think gLp from L-cells
What intestinal cells is GIP derived from?
Intestinal K cells
What is a role of incretin gut hormones GLP-1 and GIP?
Increase insulin release from beta cells and decrease glucagon from alpha cells
What does the incretin effect show?
Insulin produced is much larger when glucose is given orally as oppose to IV
What happens to the incretin effect in people with type 2 diabetes?
There is a diminished incretin effect
What effect does GLP-1 have on the brain?
Promotes satiety and reduces appetite
What effect does GLP-1 have on the stomach?
helps regulate gastric emptying - slowing down gastric emptying means insulin can better match the glucose entering the system
What effect does GLP-1 have on the pancreas
- Increased insulin secretion
- decreases glucagon secretion
Name an example of a GLP-1 receptor agonist
Exenatide
Liraglutide
Albiglutide
Dulaglutide
Who would you not give GLP-1 receptor agonists to?
Alcoholics, people with gallstone problems etc. as it has an association with pancreatitis
What class of drug is Lixisenatide?
GLP-1 receptor agonist
What is the mechanism of action of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors?
Prevent re-absorption of glucose in the kidney
What are empagliflozin, canagliflozin and dapagliflozin examples of?
SGLT-2 inhibitors
What are the two types of insulin action?
Quick/short acting
Intermediate/long-acting
In biphasic insulin mixtures, what tends to make up the larger quantity - quick or intermediate acting insulin?
Intermediate acting
Name 3 potential side effects of insulin
1) Hypoglycaemia
2) Allergic reaction - rare
3) Lipohypertrophy - accumulation of fat at site of injection
