Sitagliptin

Question 1

Define hypoglycaemia and hyperglycaemia

Answer 1

low and high blood sugar

Question 2

What is glycogen?

Answer 2

the polysaccharide used to store glucose

Question 3

What is glucagon?

Answer 3

a hormone produced by pancreatic alpha cells that causes the breakdown of glycogen to glucose

Question 4

What is insulin?

Answer 4

a hormone produced by pancreatic B cells which casues uptake of glucose from the blood

Question 5

what is released when carbohydrates are eaten?

Answer 5

insulin

Question 6

What % do type 1 and 2 diabetes account for?

Answer 6

10% and 90%

Question 7

Describe type 1 diabetes

Answer 7

no insulin is produced due to an autoimmune response and blood glucose level increases

Question 8

What are the symptoms of type 1 and 2 diabetes?

Answer 8

Urinating, genital itching, thrush, blurred vision, tiredness, weightloss

Question 9

What are the age risks for type 2 diabetes?

Answer 9

over 40 for whites, over 25 for south asians

Question 10

Describe type 2 diabetes

Answer 10

not enough insulin/insulin not working properly. Only some glucose gets into cells as fat blocks some receptors. More insulin is produced and glucose levels increase. Stored glucose can be released.

Question 11

What is the greatest risk factor of type 2 diabetes and what % risk does this account for?

Answer 11

Obesity accounts for 80-85% of overall risk

Question 12

How many people in the UK are obese?

Answer 12

about 2/3

Question 13

Diabetes is the 5th most common cause of death in the world. True or false

Answer 13

True

Question 14

What is the life expectancy reduced by for type 1 and 2 diabetes?

Answer 14

20 years and 10 years

Question 15

How much is spent by the NHS on diabetes each year?

Answer 15

£10b

Question 16

What are biguanides?

Answer 16

insulin sensitisers and guanidine derivative

Question 17

What is the active principal in biguanides?

Answer 17

Galegin

Question 18

What is the issue with guanidines?

Answer 18

safety issues and discontinued when insulin became available

Question 19

what is the advantage of biguanides over guanides?

Answer 19

better tolerability

Question 20

what is the disadvantage of biguanides?

Answer 20

risk of lactic acidosis (lowest for metformin)

Question 21

What is the first line of treatment for type 2 diabetes?

Answer 21

Metformin

Question 22

How do alpha glucosidase inhibitors work?

Answer 22

act as reversible, competitive inhibitors of alpha glucosidase and pancreatic alpha amylase

Question 23

How do alpha glucosidase inhibitors work?

Answer 23

act as reversible, competitive inhibitors of alpha glucosidase and pancreatic alpha amylase

Question 24

what are alpha glucosidase inhibitors used to control?

Answer 24

postprandial hyperglycaemia in type 2 diabetes

Question 25

where are alpha glucosidases found?

Answer 25

on the microvilli of the intestine

Question 26

what do alpha glucosidases do?

Answer 26

break down disaccharides into monosaccharides such as glucose and fructose that can be absorbed

Question 27

what is the effect of inhibiting alpha glucosidases?

Answer 27

delays digestion of carbohydrate eg sucrose and starch so delays the absorption of glucose into the bloodstream, reducing postprandial glucose and insulin secretion

Question 28

What is sulphonylureas

Answer 28

act as insulin secretagogues

Question 29

Define competitive inhibition

Answer 29

where binding of the inhibitor prevents binding of the substrate

Question 30

what are the advantages of sulphonyl ureas?

Answer 30

low cost, good efficacy, well understood side effects

Question 31

what is the mode of action of sulphonyl ureas?

Answer 31

target working B cells in the pancreas

Question 32

what are the main side effects of sulphonyl ureas?

Answer 32

hypoglycaemia due to insulin production, weight gain and cardiovascular safety issues

Question 33

What are glinides?

Answer 33

Newer insulin secretagogues

Question 34

what is the advantage of glinides over sulphonyl ureas?

Answer 34

lower capacity for hypoglycaemia

Question 35

How was and is insulin produced?

Answer 35

Animal sources, now in recombinant bacteria

Question 36

why can’t insulin be taken orally?

Answer 36

it would be broken down by proteases in the digestive tract

Question 37

what is the trade name of sitagliptin?

Answer 37

Januvia

Question 38

what combination therapy is available for sitagliptin and what is the trade name of this?

Answer 38

sitagliptin and metformin called Janumet

Question 39

what combination therapy is available for sitagliptin and what is the trade name of this?

Answer 39

sitagliptin and metformin called Janumet

Question 40

Describe the mode of action of sitagliptin

Answer 40

glucose stimulates release of incretins GLP-1 and GIP which stimulate insulin release and suppress glucagon secretion. They are degraded by DPP-4 which is inhibited by Januvia, increasing active incretins. This increases insulin synthesis/release and suppresses glucagon in a glucose dependent manner. glucose is taken up into peripheral tissues

Question 41

how does sitagliptin avoid hypoglycaemia?

Answer 41

no glucose, no incretins so sitagliptin wont work which contrasts to the older ones

Question 42

What is the advantage of the second generation synthesis of sitagliptin?

Answer 42

biocatalytic process using transaminase enzyme so no need for expensive Rh catalyst.

Question 43

Who developed sitagliptin and when?

Answer 43

Merck in 2006