Sitagliptin Flashcards
Define hypoglycaemia and hyperglycaemia
low and high blood sugar
What is glycogen?
the polysaccharide used to store glucose
What is glucagon?
a hormone produced by pancreatic alpha cells that causes the breakdown of glycogen to glucose
What is insulin?
a hormone produced by pancreatic B cells which casues uptake of glucose from the blood
what is released when carbohydrates are eaten?
insulin
What % do type 1 and 2 diabetes account for?
10% and 90%
Describe type 1 diabetes
no insulin is produced due to an autoimmune response and blood glucose level increases
What are the symptoms of type 1 and 2 diabetes?
Urinating, genital itching, thrush, blurred vision, tiredness, weightloss
What are the age risks for type 2 diabetes?
over 40 for whites, over 25 for south asians
Describe type 2 diabetes
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.
What is the greatest risk factor of type 2 diabetes and what % risk does this account for?
Obesity accounts for 80-85% of overall risk
How many people in the UK are obese?
about 2/3
Diabetes is the 5th most common cause of death in the world. True or false
True
What is the life expectancy reduced by for type 1 and 2 diabetes?
20 years and 10 years
How much is spent by the NHS on diabetes each year?
£10b
What are biguanides?
insulin sensitisers and guanidine derivative
What is the active principal in biguanides?
Galegin
What is the issue with guanidines?
safety issues and discontinued when insulin became available
what is the advantage of biguanides over guanides?
better tolerability
what is the disadvantage of biguanides?
risk of lactic acidosis (lowest for metformin)
What is the first line of treatment for type 2 diabetes?
Metformin
How do alpha glucosidase inhibitors work?
act as reversible, competitive inhibitors of alpha glucosidase and pancreatic alpha amylase
How do alpha glucosidase inhibitors work?
act as reversible, competitive inhibitors of alpha glucosidase and pancreatic alpha amylase
what are alpha glucosidase inhibitors used to control?
postprandial hyperglycaemia in type 2 diabetes
where are alpha glucosidases found?
on the microvilli of the intestine
what do alpha glucosidases do?
break down disaccharides into monosaccharides such as glucose and fructose that can be absorbed
what is the effect of inhibiting alpha glucosidases?
delays digestion of carbohydrate eg sucrose and starch so delays the absorption of glucose into the bloodstream, reducing postprandial glucose and insulin secretion
What is sulphonylureas
act as insulin secretagogues
Define competitive inhibition
where binding of the inhibitor prevents binding of the substrate
what are the advantages of sulphonyl ureas?
low cost, good efficacy, well understood side effects
what is the mode of action of sulphonyl ureas?
target working B cells in the pancreas
what are the main side effects of sulphonyl ureas?
hypoglycaemia due to insulin production, weight gain and cardiovascular safety issues
What are glinides?
Newer insulin secretagogues
what is the advantage of glinides over sulphonyl ureas?
lower capacity for hypoglycaemia
How was and is insulin produced?
Animal sources, now in recombinant bacteria
why can’t insulin be taken orally?
it would be broken down by proteases in the digestive tract
what is the trade name of sitagliptin?
Januvia
what combination therapy is available for sitagliptin and what is the trade name of this?
sitagliptin and metformin called Janumet
what combination therapy is available for sitagliptin and what is the trade name of this?
sitagliptin and metformin called Janumet
Describe the mode of action of sitagliptin
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
how does sitagliptin avoid hypoglycaemia?
no glucose, no incretins so sitagliptin wont work which contrasts to the older ones
What is the advantage of the second generation synthesis of sitagliptin?
biocatalytic process using transaminase enzyme so no need for expensive Rh catalyst.
Who developed sitagliptin and when?
Merck in 2006
