insulin 2 Flashcards
oral hypoglycaemic agents
many mechanisms of action and most patients have worsening glycemic control over time
2-3 drugs often needed
insulin
majority will eventially need insulin
hypoglycaemic drugs slowing gluconeogenesis at the liver
metformin
TZDs
drugs acting to increase insulin secretion at the pancreas
sulphonylureas
meglitinides
incretin based therapies
drugs increasing peripheral glucose uptake
TZDs
drugs slowing polysaccharide digestion at the gut
a-glucosidase inhibitors
metformin
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
pharmacokinetics of metformin
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
sulfonylureas
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
pharmacokinateics on sulfonylureas
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
benefits of sulfonylureas
robust glucose reduction
cheap and effective
side effects and cautions of sulfonureas
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
a-glucosidase inhibitors
acarbose, migilitol
- oligosaccharides of microbial origin
mechanism of action of a glucosidase inhibitors
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
side effects of a-glucosidase inhibitors
bloating and flatulence
contraindicated in severe renal failure
thiazolidinediones
TZDs
eg. pioglitazone
mechanism of action - act on nuclear receptor which activates gene transcription to improve insulin sensitivity
improves lipid profiles
thiazolidinediones
TZDs
eg. pioglitazone
mechanism of action - act on nuclear receptor which activates gene transcription to improve insulin sensitivity
improves lipid profiles
side effects of TZDs
adipogenesis - fat gain
fluid retention - heart failure
contraindicated in symptomatic heart failure
osteoporosis
incretin based therapies
incretins - gut peptides increasing insulin release after a meal
incretin response is reduced in T2DM
incretin effect
tthere is greater glucose respond when glucose is administered orally than when given intravenously
GLP-1
glucagon like peptide 1
short half life because its broken down by DPP1
GLP1 receptor agonists
peptides given subcutaneously
eg. exenatide
DPP4 inhibitors
prevent destruction of GLP1
can be given orally
eg. sitagliptin
GLP1 receptor agonist and DPP4 inhibitors benefits
increase insulin release in a glucose dependant manner
incretin based therapies benefits
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
side effects of incretin based therapies
nausea and vomiting
contraindicated with a history of pancreatitis or pancreatic cancer
adjust dose with moderate-severe renal impairment
SGLT2 inhibitors
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
side effects of SGLT2 inhibitors
low risk of hypoglycaemia
polyuria causing dehydration and dizziness
genitourinary infections eg. candida
euglycaemic DKA
insulin uses in T2DM
contraindicated in young patient or if there is evidence of microvascular disease
bariatric surgery
treatment for BMI >35
curative in kids with T2D
results in improved glycaemic control
may remove need for drug treatment altogether
therapeutic adherence
many side effects reduce adherence
