insulin 2

Question 1

oral hypoglycaemic agents

Answer 1

many mechanisms of action and most patients have worsening glycemic control over time
2-3 drugs often needed

Question 2

insulin

Answer 2

majority will eventially need insulin

Question 3

hypoglycaemic drugs slowing gluconeogenesis at the liver

Answer 3

metformin

TZDs

Question 4

drugs acting to increase insulin secretion at the pancreas

Answer 4

sulphonylureas
meglitinides
incretin based therapies

Question 5

drugs increasing peripheral glucose uptake

Answer 5

TZDs

Question 6

drugs slowing polysaccharide digestion at the gut

Answer 6

a-glucosidase inhibitors

Question 7

metformin

Answer 7

decreases hepatic gluconeogenesis 
may cause release of GLP1 (incretin effect) 
does not cause hypoglycaemia 
does not stimulate appetite 
improves lipid profile 
may have anti cancer benefits

Question 8

pharmacokinetics of metformin

Answer 8

excreted unchanged in urine 
few drug interactions because not metabolised in the liver 
GI - transient anorexia and diarrhoea 
vitamin B12 deficiency
lactic acidosis - extremely rare 
contraindicated in severe renal failure

Question 9

sulfonylureas

Answer 9

insulin secretagogues bind SSUR1 on beta cells which is a potassium channel
when blocked this stimulates insulin to be released
need functional beta cells - won’t work in T1DM or in advance T2 disease

Question 10

pharmacokinateics on sulfonylureas

Answer 10

bind albumin, metabolised in liver and excreted in urine
drug interaction - very common and increases hypoglycaemic effect
interactions with albumin binding competitors - salicylates, sulphonamides, warfarin
CYP2C9 metabolism - NSAIDs, warfarin, alcohol, sulphonamides

Question 11

benefits of sulfonylureas

Answer 11

robust glucose reduction

cheap and effective

Question 12

side effects and cautions of sulfonureas

Answer 12

hypoglycaemia - avoid using long half life drug in elderly, renal failure, alcoholism
cause weight gain because they’re appetite stimulants
contraindicated in liver failure - hepatic metabolism
start at low side and up-titrate

frequently co-administered with metformin, the drug of first choice for patients unable to take metformin

Question 13

a-glucosidase inhibitors

Answer 13

acarbose, migilitol

- oligosaccharides of microbial origin

Question 14

mechanism of action of a glucosidase inhibitors

Answer 14

mechanism of action

• competitive inhibitors of intestinal a-glucosidase
• inhibit breakdown of maltose to glucose
• delay CHO absorption, control post prandial hyperglycaemia
• act locally and not absorbed
• regularly co-prescribed with metformin and sulfonylureas

Question 15

side effects of a-glucosidase inhibitors

Answer 15

bloating and flatulence

contraindicated in severe renal failure

Question 16

thiazolidinediones

Answer 16

TZDs
eg. pioglitazone
mechanism of action - act on nuclear receptor which activates gene transcription to improve insulin sensitivity
improves lipid profiles

Question 16

thiazolidinediones

Answer 16

TZDs
eg. pioglitazone
mechanism of action - act on nuclear receptor which activates gene transcription to improve insulin sensitivity
improves lipid profiles

Question 17

side effects of TZDs

Answer 17

adipogenesis - fat gain
fluid retention - heart failure
contraindicated in symptomatic heart failure
osteoporosis

Question 18

incretin based therapies

Answer 18

incretins - gut peptides increasing insulin release after a meal
incretin response is reduced in T2DM

Question 19

incretin effect

Answer 19

tthere is greater glucose respond when glucose is administered orally than when given intravenously

Question 20

GLP-1

Answer 20

glucagon like peptide 1

short half life because its broken down by DPP1

Question 21

GLP1 receptor agonists

Answer 21

peptides given subcutaneously

eg. exenatide

Question 22

DPP4 inhibitors

Answer 22

prevent destruction of GLP1
can be given orally
eg. sitagliptin

Question 23

GLP1 receptor agonist and DPP4 inhibitors benefits

Answer 23

increase insulin release in a glucose dependant manner

Question 24

incretin based therapies benefits

Answer 24

some evidence that they increase beta cemm function and mass and stimulate beta cell ceognenesis slows gastric emptying and satiety to promote weight loss low risk hypoglycaemia decrease CVD and albuminuria die to improved glycaemic control

Question 25

side effects of incretin based therapies

Answer 25

nausea and vomiting contraindicated with a history of pancreatitis or pancreatic cancer adjust dose with moderate-severe renal impairment

Question 26

SGLT2 inhibitors

Answer 26

dapagliflozin, empagliflozin newly available treatment mechanism of action - filtered glucose is taken up by SGLT2, so when these are inhibited glucose reuptake is prevented and glucose is lost to urine causes glycosuria decreases blood glucose, blood pressure and causes weight loss

Question 27

side effects of SGLT2 inhibitors

Answer 27

low risk of hypoglycaemia polyuria causing dehydration and dizziness genitourinary infections eg. candida euglycaemic DKA

Question 28

insulin uses in T2DM

Answer 28

contraindicated in young patient or if there is evidence of microvascular disease

Question 29

bariatric surgery

Answer 29

treatment for BMI >35 curative in kids with T2D results in improved glycaemic control may remove need for drug treatment altogether

Question 30

therapeutic adherence

Answer 30

many side effects reduce adherence