Anti-diabetic drugs

Question 1

structure of biological insulin

Answer 1

cleavage of C-chain from proinsulin forms insulin that contains A and B chain

Question 2

receptor target of insulin

Answer 2

binds to GLUT4 receptor on muscle and far cells

Question 3

different type of glucose transporters (where they’re found + function + affinity)

Answer 3

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

Question 4

function of insulin

Answer 4

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

Question 5

name the different types of insulin

Answer 5

rapid acting: lispro, aspart, glulicine

short acting: regular insulin

intermediate acting: neutral protamine hagedorn

long acting: detemir and glargine

ultra long acting: degludac

Question 6

lispro, aspart and glulicine (type, administration and peak)

Answer 6

rapid acting insulin given only via SC

take it 15 mins before a meal and peaks about 1.5-2 hours after

Question 7

regular insulin (type, administration and peak)

Answer 7

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

Question 8

neutral protamine dagedorn (type, administration and peak)

Answer 8

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

Question 9

detemir and glargine (type, administration and peak)

Answer 9

long acting insulin given via SC

peakless but lasts for 18-24 hours

has low variability between patients and lower hypoglycaemia risk

Question 10

degludac (type, administration and peak)

Answer 10

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

Question 11

what insulins can or cannot be mixed?

Answer 11

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

Question 12

factors influencing PK of insulin after SC injection

Answer 12

1. where it was injected
   - abdomen better than anywhere else due to differences in blood flow
2. how deep it was injected
   - muscle layer better than dermal layer due to better vascularisation
3. how much was injected
   - larger volumes delay absorption
4. exercise before?
   - increase blood flow to the area means better absorption
5. massage site after?
   - stimulating heat means better absorption

Question 13

side effects of insulin

Answer 13

1. hypoglycaemia crisis

2. lipodystrophy/lipohypertrophy at the injection site

Question 14

management of T1 DM

Answer 14

Aim: to mimic normal pancreatic insulin secretion

ultra long acting for basal insulin + rapid acting for prandial insulin

Question 15

management of T2 DM

Answer 15

lifestyle modifications first and only given insulin if they are symptomatic or severely hyperglycaemia

Question 16

complications of insulin

Answer 16

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

Question 17

name the different types of oral hypoglycaemic agents (should have 5)

Answer 17

1. to decrease intestinal absorption and hepatic production of glucose: sensitisers e.g. metformin
2. to decrease intestinal absorption: alpha-glucosidase inhibitors e.g. acarbose
3. to increase glucose excretion: SGLT-2 inhibitor e.g. something-flozin
4. to increase insulin by acting like glucose: insulin synagogues e.g. gli-somethings
5. to increase insulin by hormone incretin: DPP4 inhibitor e.g. something-gliptin

Question 18

metformin (drug class, MOA, administration and note)

Answer 18

Drug class: sensitiser

MOA: decrease intestinal glucose absorption and hepatic glucose production

Administered: orally

Note: only works when there is circulating functional insulin

Question 19

acarbose

Answer 19

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

Question 20

something-flozins

Answer 20

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

Question 21

gli-somethings

Answer 21

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

Question 22

something-gliptin

Answer 22

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

Question 23

standard therapy

Answer 23

metformin with other add-ons if necessary

Question 24

can you give acarbose with metformin?

Answer 24

no, because it will both cause GI discomfort and acarbose will interfere with metformin absorption

Question 25

what do you use in patients with renal impairment?

Answer 25

DPP4 inhibitors e.g. something-gliptin

Question 26

what do you preferentially use in patients with CVD?

Answer 26

SGLT-2 inhibitor e.g. something-flozin

Question 27

additional beneficial effects of metformin, making it a gold standard therapy

Answer 27

also helps with weight loss and decrease TG levels

Question 28

general side effects of oral hypoglycaemic agents

Answer 28

1. hypoglycaemia

2. liver damage (especially alpha-glucosidase inhibitor and insulin synagogues)