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