T2DM drugs Flashcards
where does insulin induce glucose uptake mainly
muscle and liver
in adipose tissue what is glucose converted to with insulin
fat
what does insulin do to amino acids
stimulated amino acids –> proteins
what are first-line lifestyle modifications in T2DM
stop smoking, diet, lower BMI, exercise
what drug types are dependent upon insulin
increase secretion of insulin (SURs, incretin mimics - meglitinides, DPP4 - gliptins), decrease insulin resistance and reduce hepatic glucose output (metformin, thiazolidinediones)
what drug types are independent of insulin
slow glucose absorption fro GI tract (alpha-glucosidase inhibitors), enhance glucose excretion via kidneys (SGLT2)
describe insulin release in beta cells (briefly)
enters via GLUT2 –> phosphorylated –> ATP by glucokinase, ATP/K channels shut –> increased K –> depolarisation –> ca channels open –> insulin secretion
what is first line drug
metformin
what type of drug is metformin
biguanides
how does metformin work (4)
reduces gluconeogenesis, increases glucose uptake in muscle, reduces carb absorption, increases fatty acid oxidation
what side effects of metformin are there
GI upset, rarely acidosis (DKA)
what is a positive side effect of metformin
weight loss
what type of drug are sulfonylureas (SURs)
insulin secretagogues so need functional beta cells
name 3 SURs
gliclazide, glipizide, tolbutamide (-ide)
how do SURs work
close K/ATP channels –> depolarisation –> insulin release
when are SURs used first line
metformin intolerant or osmotic symptoms
what are side effects of SURs
hypoglycaemia, weight gain
what are contraindications for hypoglycaemia ie SURs
elderly, renal impairment, pregnant, professional drivers (DVLA strict rules)
what is a positive side effect of SURs
good for heart
when do SURs peak
after 1-2 hours
name 2 glinides/ meglinitides
repaglinide, mateglinide, - glinide
how do glinides work
similar to SURs but augmented by glycaemia, close KATP channels (not really used)
when do glinides kick in
fast onset 30-60 mins
what are contraindications of glinides
severe hepatic impairment, pregnancy and breast feeding
name a thiazolidinediones/ TZDs/ glitazones
pioglitazone only one used now
how do glitazones work
enhance insulin action at target (no effect on secretion), agonist of TF that promotes insulin signalling
what effects do glitazones have
fatty acid uptake to apidocytes, reduce hepatic output
what are adverse affects of glitazones
weight gain, fluid retention, bone fractures
what peptides are released from the intestine in the incretin effect
glucagon like peptide-1 (GLP1) and glucose dependent insulinotropic peptide (GIP)
describe the incretin effect
GLP1 and GIP released from intestine into blood, GLP1 and GIP enhance insulin release, GLP1 decreases glucagon release
what breaks down GLP1 and GIP
DPP4
what are incretin analogues. GLP1 agonists
peptides that miic action of GLP1 but resist breakdown by DPP4
give an example of an incretin mimic/ GLP1 agonist
exenatide
how are incretin analogues. GLP1 agonists given
subcut injections
what are side effects of incretin analogues/ GLP1 agonists
nausea, pancreatitis, very short half life - not long acting
name a DPP4 inhibitors/ gliptins
sitagliptin, -gliptin
how do DPP4is/ gliptins work
competitively inhibit DPP4 which therefore increases GLP1 and GIP
what are downsides of gliptins
not very effective, can cause nausea
how do SGLT2 inhibitors work
selectively blocks reabsorption by SGLT2 deliberately causing glucosuria
name and SGLT2 inhibitor
dapagliflozin
name a side effect of SGLT2i’s
UTIs
how do alpha glucosidase inhibitors work
breaks down starch to absorbable glucose, inhibitors stop this happening in intestines
name 2 alpha glucosidase inhibitors
acarbose, voglibose, -bose
what are side effects of alpha glucosidase
GI symptoms, not very effective
what drugs cause weight gain
SUR’s and piogliazatone
what drugs cause weight loss
metformin, SGLT2i, GLP1 agonists
what drugs are good for the heart
metformin, SGLT2i
what drugs cause hypoglycaemic risk
SURs, insulin
what drugs are safest in CDK
pioglitazone, GLP1 agonists, insulin (NOT SLGT2i)
what drug causes fractures and oedema
pioglitazone
what is orlistat
inhibits lipases and stops absorption of fat
which bariatric surgery is most malapsorptive
route en Y
which bariatric surgery can slip
adjustable bands
