Drugs used in the treatment of diabetes Flashcards
How is metformin metabolised?
It’s not metabolised and excreted unchanged in the urine.
It is undetectable in plasma 24hrs after a single dose.
Can overdose of metformin cause lactic acidosis?
Yes
What is the duration of action of metformin?
Duration of action is between 8 & 12 hours, and is therefore administered up to 3 times a day.
Peak concentrations are reached within one to three hours
What is metformin?
Metformin is a Biguanide hypoglycaemic agent.
It enhances the peripheral action of insulin (endogenous), decreases intestinal glucose uptake & decreases peripheral glucose utilisation.
Can metformin cause ketonuria?
Yes
Are biguanides teratogenic?
No but are not recommended in pregnancy
Can metformin be given to any patient?
Ketonuria can occur in young diabetics treated with Insulin & Biguanides, and so Metformin is usually only used in adult onset diabetes.
What is the oral bioavailability of metformin?
50-60%
How protein bound is metformin?
Negligible protein binding
What is the average half life of biguanides?
The average half-life is 3 hours but the hypoglycaemic effect can last to between 6 & 14 hours.
What is the action of sulphonylureas?
Eg gliclazide
Used in adult onset diabetes. They increase insulin release from pancreatic beta cells (but not production).
Do not cause lactic acidosis.
Can cause hypoglycaemic episodes and blood sugars must be checked regularly. They also enhance Insulin’s effect of taking up glucose into muscle & fat.
Other examples include glibenclamide, tolbutamide &, the older preparation, chlopropramide.
Can sulphonylureas be used in pregnancy?
No
What is the MOA of sulphonylureas?
They act by binding to a receptor coupled to increased Calcium entry into the pancreatic beta cells, which enhances Insulin secretion.
Are sulphonylureas potentiated by sulphonamides?
Yes
Which has the longer half life - buguanides or sulphonylureas?
Sulphonylureas have longer half lives than the Biguanides
How do thiazide diuretics interact with sulphonylureas?
THiazides antagonise the hypoglycaemic effect of sulphonylureas
Are sulphonylureas highly protein bound?
Yes
What effect do sulphonylureas have on bound insulin?
Act by displacing bound Insulin from the pancreatic islet 13 cells
(&, therefore, they are only effective if endogenous insulin still exists (i.e. not absolute insulin loss/pancreatic beta cell destruction, as in type 1 DM).
How can sulphonylureas be given?
Only orally. No IV preparation.
Which sulphonylureas can cause pancytopenia?
Tolbutamide & Chlorpropramide can cause leucopenia, agranulocytosis and thrombocytopenia in rare cases
What is the metabolism of chlorpropramide?
Chlorpropramide undergoes no significant metabolism & is excreted, very slowly, largely unchanged in the urine.
Does gliclazide protect pancreatic beta cells from hyperglycaemic damage?
Yes
Does gliclazide affect atheromatous build up?
Yes it reduces it
What is the pH of neutral insulin?
7
Is insulin affected by binding to IV fluid container & tubing?
Yes. 60-80% can be lost this way
How much of secreted insulin is degraded by liver & kidneys?
80%
The liver enzyme, hepatic glutathione transhydrogenase breaks the insulin molecule down into it’s constituent peptide chains.
What is the half life of endogenous insulin?
Endogenous insulin has a very short half life of 10 - 20 mins and is fixed to many tissues, except RBCs & brain.
How many chains is insulin made of?
It has a molecular weight of 5600 Da and is composed of 2 polypeptides, called A and B chains, strongly bound by 2 covalently bonded disulphide bridges.
What is the MOA of insulin?
Insulin decreases cAMP (involves 2nd messanger system) in the liver and causes a shift of potassium intracellularly, therefore effectively decreasing serum potassium levels in acute hyperkalaemia.
It also inhibits hormone sensitive lipase, increases protein synthesis in ribosomes and increases glucose uptake in the peripheral tissues.
Where does insulin facilitate glucose uptake into?
- the pituitary
- peripheral tissues incl muscle and fat
- the liver (glycogen)
- fibroblasts
- It decreases reabsorption in the intestine, which can lead to glycosuria
What anticholinergic can block insulin secretion?
Atropine
What hormone will inhibit insulin secretion?
Somatostatin
What effect does theophylline have on insulin?
Stimulates insulin secretion
What effect does leucine and arginine (amino acids) have on insulin secretion?
Stimulates insulin secretion
What effect does the sympathetic nervous system have on insulin secretion?
The Sympathetic nervous system has conflicting effects on Insulin release, Alpha 2 agonists decrease Insulin release, whilst Beta 2 agonists increase it’s secretion.
