Diabetes Podcast 3-5 Flashcards
2nd gen ___ are more potent than 1st
Sulfonylureas
After a meal, a rise in BG results in glucose
Glucose metabolized, inc ATP to close
when ATP low
high
B cells become
Due to block of
Depolariztion inc Ca2+ influx through
Ca2+ causes the fusion of insulin ____ to the membrane, resulting in
transport into panc B cells
ATP dep K channels
channels open
channels close
Depolarized
K efflux
voltage sensitive Ca2+ channels
stroage vesicles, insulin release
SFU/Glinides stimulate insulin release from B cells by
Side effects
SFU drop A1C by
drop FPG by
Use as ____ therapy to pt unable to achieve target BG goals on
considered 1st line in pt w contraindication to
blocking ATP dep K channels
WG, hypoglycemia
1.5-2%
50-60 mg
add on, metformin
metformin
SFU absorbed well in
___ delays time to peak action
Signif binding to
Metabolized by
Excreted by
Duration of action (Glyburide, Glmepiride)
GI
Food/hypergly
plasma proteins
liver
kidney
10-24
Drugs that may reduce effects of SFU (lost glucose control)
impair
Drugs that potentiate SFU effects (hypoGly)
displace SFU ____
Thiazides, CCB
mechanism
Salicylates, aspirin, sulfa
binding
SFU AE
BC SFU has long duration, hypoGly can be
____ causes less hypoGly
account for most ___ in elderly
Contraidnications T P/BF H H/R
hypogly
protracted
Glimepiride
hypoGly
T1DM
Preg, BF= cross placenta, deplete fetal insulin
Hypersensitivity to sulfa
Hepatic/renal dysfxn
SFU considered
Pt predisposed to SFU induced hypoglycemia
Risk for mortality greater with
Glimepiride more selective for
SFU can dec
may cause MI bc interaction w
oral hypoglycemic
Elderly, high dose SFU, renal impairment, hypoglycemic unawareness
Glyburide than Glimepiride
panc ATP dep K channels
macrovasc comps (reduce MI)
ATP dependent K channels in heart
Meglitinides dec A1C by
Dec
which is preferred
Clinical use P Used as \_\_\_ to metformin Can be used Pt w A1C < \_\_\_ responds better Dosed at
1-1.5%
PP hyperGly
Repaglinide
PP hyperGly add on alone 8% mealtimes
Meglitinides
___ onset and ___ DOA
good absorption
absorption delayed if taken
Metabolized by
Excretion by ___, N/R
W renal insuff, caution use w
___ more appropriate
Rapid, onset
0-30 before meal
after meal
different liver CYPs
kidney, 80/10
Nateglinide
Repaglinide
Meglinitides AE
More w
N has __ onset but ___ sec of insulin
Drugs that interfere w ___ metabolism via __ can inc risk for
HypoGly, wg
Repaglinide
rapid, less sustained
Repaglinide, CYP3A4, hypogly
Factors contributing to T2DM
Metformin and TZD can ___ insulin resistnace, ___ tissues, and restore
Insulin resistance in peripheral tissue leads to ____ prod of glucose
insulin resistnace + dec sec
dec, re-sensitize, normal fxn
increase
Metformin MOA
Activates __ in liver/muscle
___ lipogenesis, fatty liver
___ hepatic insulin sensitivity
Can reduce ____ to dec glucose output
inc AMPK leads to
___ gene expression of enzyes in gluco
___ gene exp of lipogenic enzymes (dec FL)
___ muscle glucose uptake by making more
dec hepatic glucose prod
AMPK (inc glucose uptake)
Dec
Inc (dec gluco, FPG)
Glucagon sec
dec
Dec
Inc, glut 4
Metformin dec A1C by
dec FPG by
Advantages
used as ____ for T2DM
___ pt
measure ___ at baseline
absorbed from
__ binding to plasma proteins
Excreted unchanged in
DOA
1.5-1.7%
50-70
no wg, hypogly
Pos effect on lipid profile (dec TG, LDL inc HDL)
1st line therapy
Prediabetic
eGFR, LFT
SI
no
urine
6hrs
Metformin contra
Conditions predisposing to inc
Such as
For kidney dz, avoid if eGFR <
OK for ____ impairment
____ procedures w iodinated dyes
Metformin should be ____ for 48hrs
confrm normal ___ fxn after dye
lactate
hepatic, renal, heart dz
hypoxic lung dz
elderly, LA, active EtOH abuse
30
mild-mod
Radiological
withheld
renal
AE of Metformin
Alcohol can potentiate metformins effect to inc
___ more likely
Sx
____ OTC H2 recep antag
blocks
inc ___
Lactate is normlly taken up by ___ and converted to
Metformin dec _____
D/A/N, metallic taste, dec VB12/folate absorp
lactate accumulation
LA
malaise, myalgia, ab discomfort, heavy breathing
Cimetidine
Stomach Acid
Metformin conc
liver, glucose
conversion to glucose
TZDs MOA
Activates _____ nuclear receptors
present in ____ sens tissues, mostly the
activation of PPAR leads to
circulating FFA leads to
Improves ability to
dec circulating
Dec TG and inc HDL better w
PPAR G
insulin, adipose
FFA storage
insulin resistance
store lipids/glucose
TG
Pioglitazone > Rosiglitazone
TZD can ___ in muscle/adipose
___ HGP
_____ onset of action is
Dec A1C by
Greatest effect on
Reverses ____
Favorable effect on
___ glycemic control
___ insulin requirements
GLUT 4
dec
delayed
1-1.5%
FPG
Insulin resistance Lipid prof (inc HDL, dec TG)
inc
Dec
TZD typically not used as
Use w
___ onset of effect
PIO/ROSI metabolized by
elim for ROSI but not PIO
AE
DOA
1st line
mod-severe metabolic syndrome
Slow
diff CYP enzymes
kidney
WG, cv risks
24hrs
TZD Precautions
___ fxn
___ In liver dz
Take ___ prior to and @ 1yr
___ retention, can exacerbate
contra in pt w
Dec
Possible
Liver (hepatotoxicity)
contraindicated
LFT
Fluid, HF
symptomatic HF
bone mineral density
bladder Ca
Alpha glucosidase inhib
MOA
reduces
dec A1C by
better at reducing
___ PPG levels
Used as
in pt w
Dosed w
dec activity of alpha gluc on intestinal BB
CHO absorption
.5%
PPG
dec
Alone/in combo
T1/T2
meals
Alpha gluco inhib
Minimally ___ and ____ by GI enzymes
DOA
AE
Measure ___ during 1st year
Contraind w
Hypogly can occur when used w
tx w
may influence ___ of co-admin drugs
absorbed, metabolized
6hrs
ab pain, flatulence, D/cramps
LFT
IBD/IBS, malabsorption
other antiDM meds
dextrose
absorption
T2DM defects
Insulin
Dec
Impaired
Impaired
results in loss of
(incretin) GI hormones released upon eating can trigger ___ before BG levels rise
____ is endo incretin
Incretin GI horones can also ___ and reduce
Drugs can ____ effects
resistance
insulin sec
glucagon sec
Incretin response
1st phase insulin response
insulin release
GLP1
slow GE, glucagon
mimic/prolong action
Incretin analogs
Oral DPP4 inhibs
IA are analogs of
DPP4 inhib works through
Exenatide/liraglutide
Sitagliptin
GLP1
preventing degredation
GLP1 analogs
MOA Restore Moderate Slow Suppress inc panc
Administered via
DOA for E/L
E excretion
SE
1st phase insulin Glucagon GE appetite B celll mass
SQ injections
shorter, 2x day/longer 1x day
Renal
N/V/D/hypoG
GLP 1 analog dec A1c by
greater effect on
Adv
use when T2DM cannot achieve
Usef as add on w ____
to avoid hypoGly ___
can be used as
1%
PPG
Wl
PPG
metformin, SFU
dec SFU Dose
monotherapy
Rare AE of GLP1 ag
Contra
Hypogly w
Reduce absorption of
May affect ___ therapy/bleeding
Antibodies to drug, hyprsensitivity rxn, acute panc, RF
Panc, impaired renal xn, thyroid ca, GI dz
other agents
coadmin drugs (ab/OC)
warfarin, inc
DPP4 effect
MOA of DPP4 inhib
Restore
Moderate
Weight
Dec A1c by
More effet on
ADV
T2DM use to control
Used as ___, w
asses ___ prior to therapy
degrade endo incretin
prolong endo GLP1
1st phase insulin
glucagon sec
netural
.5%
oral, fewer SE
PPG
add on/mono- metformin/SFU/insulin
eGFR
DPP4 inhib absorbed
excreted by
Half life
AE effect
possible
another drug in class
Rapid
kidney
6-12hr
hypersens- SJS/angio/anaphyl
panc metaplasia\
saxagliptin
Amylin analog
___ secreted by B cells along w insulin
MOA
suppresses
Dec A1c by
used as ___ for
targets
dose w
co administer w
panc hormone
delay gastric emptying
glucagon
.3-.6%
add on
PPG
meals
insulin, SFU
SE of amylin analog
Contraindic
Avoid w
GI sx, hypogly
hypogly unawareness, GI dz
heavy machines/high risk acts
SGLT2 inhib
SGLT2 contransports
expressed in
mediates reabsorption of
drugs work to
dec A1C by
ADV
Na-Glucosee
proximal tubule
90% filtered load of glucose
promote renal exc, lower BG
.5-.7%
wl, dec BP
SGLT2 inhib absorbed
___ DOA
___ requires adjustment
\_\_ _genital/UTI D inc \_\_\_ sec K w BG less than 200 Dec
rapidly
long
CKD
inc dehydration glucagon KA BMD (inc PO4 reabsorp)
