Anti-diabetic drugs Flashcards
structure of biological insulin
cleavage of C-chain from proinsulin forms insulin that contains A and B chain
receptor target of insulin
binds to GLUT4 receptor on muscle and far cells
different type of glucose transporters (where they’re found + function + affinity)
GLUT 1: found in all tissues for basal glucose uptake (high affinity)
GLUT 2: found in liver and pancreas (beta cells) - insulin independent glucose uptake (low affinity)
GLUT 3: found in all tissues for basal glucose uptake (high affinity)
GLUT 4: found in all muscles and fat cells - insulin dependent glucose uptake (medium affinity)
GLUT 5: found in small intestine
function of insulin
anabolic effect = using plasma blood glucose to make things
carbohydrate anabolism: glycogenesis, inhibits gluconeogenesis and glycolysis
lipid anabolism: lipogenesis, inhibits lipolysis
protein anabolism: protein synthesis, inhibits protein degradation
name the different types of insulin
rapid acting: lispro, aspart, glulicine
short acting: regular insulin
intermediate acting: neutral protamine hagedorn
long acting: detemir and glargine
ultra long acting: degludac
lispro, aspart and glulicine (type, administration and peak)
rapid acting insulin given only via SC
take it 15 mins before a meal and peaks about 1.5-2 hours after
regular insulin (type, administration and peak)
short acting insulin given via SC, IM or IV
take 20-30 mins before a meal and peaks 2-4 hours after
can be given via IV during hyperglycaemia crisis
neutral protamine dagedorn (type, administration and peak)
intermediate acting insulin given via SC
peaks 4-8 hours after as there is the protamine component from trout semen to protect the insulin
has great variability between patients and hence increased hypoglycaemia risk
detemir and glargine (type, administration and peak)
long acting insulin given via SC
peakless but lasts for 18-24 hours
has low variability between patients and lower hypoglycaemia risk
degludac (type, administration and peak)
ultra long acting insulin given via SC
peakless but has basal insulin secretion over 42 hours - how it lasts so long is because it forms a multihexamer at physiological pH
long duration but is hard to adjust day-to-day
what insulins can or cannot be mixed?
can:
- NPH (intermediate acting) + rapid/short acting
- degludac + rapid acting [best]
cannot:
any long acting insulins cannot be mixed as it changes the pH and component
factors influencing PK of insulin after SC injection
- where it was injected
- abdomen better than anywhere else due to differences in blood flow - how deep it was injected
- muscle layer better than dermal layer due to better vascularisation - how much was injected
- larger volumes delay absorption - exercise before?
- increase blood flow to the area means better absorption - massage site after?
- stimulating heat means better absorption
side effects of insulin
- hypoglycaemia crisis
2. lipodystrophy/lipohypertrophy at the injection site
management of T1 DM
Aim: to mimic normal pancreatic insulin secretion
ultra long acting for basal insulin + rapid acting for prandial insulin
management of T2 DM
lifestyle modifications first and only given insulin if they are symptomatic or severely hyperglycaemia
complications of insulin
look out for patients under high stress or on chronic steroids
in such patients, blood glucose tend to be higher due to increased metabolism and hence need to adjust insulin dosags
name the different types of oral hypoglycaemic agents (should have 5)
- to decrease intestinal absorption and hepatic production of glucose: sensitisers e.g. metformin
- to decrease intestinal absorption: alpha-glucosidase inhibitors e.g. acarbose
- to increase glucose excretion: SGLT-2 inhibitor e.g. something-flozin
- to increase insulin by acting like glucose: insulin synagogues e.g. gli-somethings
- to increase insulin by hormone incretin: DPP4 inhibitor e.g. something-gliptin
metformin (drug class, MOA, administration and note)
Drug class: sensitiser
MOA: decrease intestinal glucose absorption and hepatic glucose production
Administered: orally
Note: only works when there is circulating functional insulin
acarbose
Drug class: alpha-glucosidase inhibitors
MOA: bind to a-glucosidase transporters in the small intestine and prevent uptake of glucose = works incredibly well to blunt post-prandial glucose
Administration: orally
Note: the remaining glucose in the small intestine is subjected to colonic fermentation = flatulence/distension
something-flozins
Drug class: SGLT-2 inhibitors
MOA: binds to SGLT-2 in the renal tubules and prevent the reabsorption of glucose = more is excreted
Administration: orally
Note: increases risk of yeast infections especially in women BUT a plus point is that it is good for those with CVD
gli-somethings
Drug class: insulin synagogues
MOA: mimics the action of glucose and binds to sulphonylurea receptors to trigger insulin exocytosis from beta cells in pancreas
Administration: orally
Note: efficacy depends on functionality of beta cells in pancreas
something-gliptin
Drug class: DPP4 inhibitors
MOA: bind to dipeptidyl-peptidase receptors and prevent the enzyme from degrading incretin = incretin effect is prolonged (insulin secretion and satiated feeling)
Administration: orally
Note: usually reserved for patients with renal impairment
standard therapy
metformin with other add-ons if necessary
can you give acarbose with metformin?
no, because it will both cause GI discomfort and acarbose will interfere with metformin absorption
what do you use in patients with renal impairment?
DPP4 inhibitors e.g. something-gliptin
what do you preferentially use in patients with CVD?
SGLT-2 inhibitor e.g. something-flozin
additional beneficial effects of metformin, making it a gold standard therapy
also helps with weight loss and decrease TG levels
general side effects of oral hypoglycaemic agents
- hypoglycaemia
2. liver damage (especially alpha-glucosidase inhibitor and insulin synagogues)
