Pharmacology Flashcards
lispro is a ___ insulin
ultra-fast/short-acting
glargine = ___ insulin
give a single bedtime dose
ultra-long acting
a biguanide
metformin
insulin sensitiser =
metformin/biguanides
usual dose of metformin
500mg od/bd
metformin: decreases HbA1c by: hypo risk? weight? complications? pregnancy?
15-20mmol/mol no hypo risk stays same or lose wt decreases micro+macrovasc complications safe in pregnancy
adverse affects of metformin
nausea, vom, abdo pain vitB12 and folic acid absorption interference lactic acidosis liver failure rash
insulin secretagogues =
sulfonylureas
sulfonylurea examples
glipizide
glicazide
glimepiride
glibenclamide/glyburide
adverse affects of sulfonylureas
hypoglycaemia
weight gain
PPAR gamma agonists =
thiazolidenediones (TZDs)
TZD example
pioglitazone
PPAR-RXR receptor in nucleus turns on genes for (4)
lipoprotein lipase
FA transport protein
FA CoA synthase
GLUT4
TZD- hypo risk? wt?
no hypo risk unless taken with SU
increases weight due to S/C fat and fluid retention
drugs that increase intestinal secretion of insulin =
incretins
GLP-1 receptor agonists examples
exenatide
exendin LAR
liraglutide
lixisenatide
benefits of GLP-1 receptor agonists
promote insulin secretion without hypos
suppress glucagon (which is raised in T2D)
early satiety
adverse affects of GLP-1 receptor agonists
nausea (resolves in 6-8wks)
pancreatitis
route of delivery of exenatide
S/C injection
DPP4 inhibitors
vildagliptin
sitagliptin
saxagliptin
linagliptin
DPP4 inhibitors are less/more potent than GLP-1 receptor agonists?
less
GLP-1 is secreted by:
GIP is secreted by:
GLP-1 = L cells GIP = K cells
benefits of DPP4 inhibitors
promote insulin secretion without hypos
decrease glucagon
weight neutral
adverse affect of DPP4 inhibitors
pancreatitis
SGLT2 inhibitors
dapagliflozin
canagliflozin
empagliflozin
diabetic drug than causes you to pee out 80g sugar each day
SGLT2 inhibitors
SGLT2 inhibitor benefit and adverse affect
benefit = weight loss adverse = increase risk of thrush and UTI
low levels of ___ increase appetite and thermogenesis but high levels dont do the reverse
leptin
drugs with insulin dependent action that cause an increase in insulin secretion
SUs
incretin mimics
glinides
DPP4 inhibitors
insulin dependent drugs that decrease insulin resistance and decrease hepatic glucose output
biguanides
TZDs
insulin independent drugs that slow glucose absorption from the gut
alpha-glucosidase inhibitors
insulin independent drugs that enhance glucose excretion from the kidney
SGLT2 inhibitors
increased blood glucose cause increased diffusion of ___ into beta cell by ____ > ___ phosphorylates glucose > increase ATP and ___ close > depolarisation and __ open >insulin secreted
glutamate GLUT2 facilitated transport glucokinase KATP channels close Ca2+ channels open
ATP binds to KIR6.2 = KATP channel ___
closes
ADP-Mg2+ binds to SUR1 = KATP channel ___
opens
SUs have a risk of hypoglycaemia because
bind to SUR1 and close KATP causing insulin release independent of bg
1st generation SU=
tolbutamide
2nd generation SU are __potent and have a ___ duration of action so a higher risk of___ than 1st generation SUs
more
longer
hypos
SUs usually given in combo with __/__
metformin
TZDs
Examples of glinides
repaglinide and nateglinide
mechanism of glinides
similar to SUs - bind to SUR1 at a benzamido site and close KATP channel
glinides have ____ which causes a reduced risk of hypos when compared to SUs
a quick onset and offset of action
when are glinides taken and by what route
PO before meals to decrease post prandial bg rise
glinides are usually in combo with __/__
metformin
TZDs
L cells that secrete ___ are found in the __+__
GLP-1
ileum and colon
K cells that secrete __ are found in the __+__
GIP
jejunum and duodenum
GLP-1 and GIP ___ insulin release and delay ___ causing ___ glucose uptake and use
increase
gastric emptying
increased
GLP-1 decreases ___ release and so decreases ___ production
glucagon
glucose
GLP-1 analogues give S/C od = and S/C bd =
od = liraglutide bd = exenatide
GLP-1 analogues bind to ___ receptors that increase ___ causing increased __ secretion, decreased __ secretion and decreased__+__
GPCR GLP1
cAMP and insulin secretion
glucagon secretion, gastric emptying and appetite
DPP4 antagonists usually in combo with __/__
TZD
metformin
mechanism of action of DPP4 antagonists
stop DPP4 terminating GLP1/GIP action = prolong their action
alpha glucosidase inhibitor example
acarbose
alpha glucosidase inhibitor mechanism of action
inhibit alph glucosidase (brush border enzyme) to stop starch and disaccharide being converted to glucose = delay glucose absorption and decrease postprandial bg rise
hypo risk with alpha glucosidase inhibitor ?
no
adverse effects of alpha glucosidase inhibitor
flatulence loose stools diarrhoea abdo pain bloating
metformin decreases hepatic ___ (stimulates __), increases skeletal muscle __+__ by increasing ___
decreases __ absorption
increases __ oxidation
gluconeogenesis (AMPK)
glucose uptake and use ; insulin signalling
carbohydrate absorption
FA oxidation
lactic acidosis is a rare but serious side effect of this drug
metformin
TZDs mechanism of action
agonise PPAR gamma - largely confined to adipocytes
= a TF that promotes gene expression of proteins involved in insulin signalling, lipoprotein lipase, FA transport protein and GLUT4
promote FA uptake and storage in adipocytes over muscle and liver
decrease hepatic glucose output
TZDs cause fluid retention because
increase Na reabsorption in the kidney
SGLT2 inhibitors block ___ in ___ of nephron
decrease ___ and cause glycosuria
SGLT2
proximal tubule
glucose reabsorption
