Drugs used in the treatment of diabetes

Question 1

How is metformin metabolised?

Answer 1

It’s not metabolised and excreted unchanged in the urine.

It is undetectable in plasma 24hrs after a single dose.

Question 2

Can overdose of metformin cause lactic acidosis?

Answer 2

Yes

Question 3

What is the duration of action of metformin?

Answer 3

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

Question 4

What is metformin?

Answer 4

Metformin is a Biguanide hypoglycaemic agent.

It enhances the peripheral action of insulin (endogenous), decreases intestinal glucose uptake & decreases peripheral glucose utilisation.

Question 5

Can metformin cause ketonuria?

Answer 5

Yes

Question 6

Are biguanides teratogenic?

Answer 6

No but are not recommended in pregnancy

Question 7

Can metformin be given to any patient?

Answer 7

Ketonuria can occur in young diabetics treated with Insulin & Biguanides, and so Metformin is usually only used in adult onset diabetes.

Question 8

What is the oral bioavailability of metformin?

Answer 8

50-60%

Question 9

How protein bound is metformin?

Answer 9

Negligible protein binding

Question 10

What is the average half life of biguanides?

Answer 10

The average half-life is 3 hours but the hypoglycaemic effect can last to between 6 & 14 hours.

Question 11

What is the action of sulphonylureas?

Answer 11

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.

Question 12

Can sulphonylureas be used in pregnancy?

Answer 12

No

Question 13

What is the MOA of sulphonylureas?

Answer 13

They act by binding to a receptor coupled to increased Calcium entry into the pancreatic beta cells, which enhances Insulin secretion.

Question 14

Are sulphonylureas potentiated by sulphonamides?

Answer 14

Yes

Question 15

Which has the longer half life - buguanides or sulphonylureas?

Answer 15

Sulphonylureas have longer half lives than the Biguanides

Question 16

How do thiazide diuretics interact with sulphonylureas?

Answer 16

THiazides antagonise the hypoglycaemic effect of sulphonylureas

Question 17

Are sulphonylureas highly protein bound?

Answer 17

Yes

Question 18

What effect do sulphonylureas have on bound insulin?

Answer 18

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).

Question 19

How can sulphonylureas be given?

Answer 19

Only orally. No IV preparation.

Question 20

Which sulphonylureas can cause pancytopenia?

Answer 20

Tolbutamide & Chlorpropramide can cause leucopenia, agranulocytosis and thrombocytopenia in rare cases

Question 21

What is the metabolism of chlorpropramide?

Answer 21

Chlorpropramide undergoes no significant metabolism & is excreted, very slowly, largely unchanged in the urine.

Question 22

Does gliclazide protect pancreatic beta cells from hyperglycaemic damage?

Answer 22

Yes

Question 23

Does gliclazide affect atheromatous build up?

Answer 23

Yes it reduces it

Question 24

What is the pH of neutral insulin?

Answer 24

7

Question 25

Is insulin affected by binding to IV fluid container & tubing?

Answer 25

Yes. 60-80% can be lost this way

Question 26

How much of secreted insulin is degraded by liver & kidneys?

Answer 26

80% The liver enzyme, hepatic glutathione transhydrogenase breaks the insulin molecule down into it's constituent peptide chains.

Question 27

What is the half life of endogenous insulin?

Answer 27

Endogenous insulin has a very short half life of 10 - 20 mins and is fixed to many tissues, except RBCs & brain.

Question 28

How many chains is insulin made of?

Answer 28

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.

Question 29

What is the MOA of insulin?

Answer 29

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.

Question 30

Where does insulin facilitate glucose uptake into?

Answer 30

* the pituitary * peripheral tissues incl muscle and fat * the liver (glycogen) * fibroblasts * It _decreases_ reabsorption in the intestine, which can lead to glycosuria

Question 31

What anticholinergic can block insulin secretion?

Answer 31

Atropine

Question 32

What hormone will inhibit insulin secretion?

Answer 32

Somatostatin

Question 33

What effect does theophylline have on insulin?

Answer 33

Stimulates insulin secretion

Question 34

What effect does leucine and arginine (amino acids) have on insulin secretion?

Answer 34

Stimulates insulin secretion

Question 35

What effect does the sympathetic nervous system have on insulin secretion?

Answer 35

The Sympathetic nervous system has conflicting effects on Insulin release, _Alpha 2 agonists_ **decrease** Insulin release, whilst _Beta 2 agonists_ **increase** it's secretion.