Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PHAR152 > Diabetes 4 > Flashcards

Diabetes 4 Flashcards

1
Q

What is the MOA of metformin?

A

not fully understood but:
-decreases hepatic glucose production
-can enhance insulin sensitivity
-increases glucose utilization via action in the gut
-has effects on the gut microbiome which may explain some anti-inflammatory effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is metformin dosed?

A

start slow: initiate at 250-500mg OD
titrate up by 500mg weekly if no GI side effects
desired usual dose: 850-1000mg BID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the max dose of metformin?

A

850mg TID (2500mg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the name of the XR version of metformin? How is it dosed?

A

Glumetza
OD or BID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is something patients should be made aware of with Glumetza?

A

ghost shells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the efficacy of metformin.

A

decreases A1C by 1-1.5% (up to 2% in drug naive with A1C of 9%)
decreases TG and LDL 8-15%
increases HDL by 2%
decreased MI and mortality in T2 patients with obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some drug interactions with metformin?

A

cimetidine (competes for renal tubular secretion)
-increases metformin levels by 60%
dolutegravir (increases metformin concentration)
alcohol (potentiates metformin’s effect on lactate metabolism)
-enhanced hypoglycemic effect
contrast media
-hold for 48hrs after imaging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the adverse effects of metformin?

A

common: GI (up to 30%, about 5% will d/c)
-DIARRHEA, nausea, abdominal discomfort
less common:
-metallic taste: only lasts a few weeks
-B12 deficiency: long term use (>5yrs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What kind of impact does metformin have on hypoglycemia? What about weight gain?

A

very low risk of hypoglycemia as monotherapy
-increased with alcohol, not eating, SU
weight neutral to modest weight loss (~1kg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

If the GI side effects of metformin are bothersome what can be done?

A

take with food or try XR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some precautions with metformin?

A

lactic acidosis: decreased arterial pH and accumulation of lactate
-weakness, malaise, myalgias, laboured breathing
-metformin inhibits conversion of lactate into glucose in liver
-more of a concern with reduced eGFR
-rare and actual association is debated
renal impairment: decreased dose if ClCr <60ml/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a scenario where the dose of metformin is reduced? Why?

A

impaired renal function
metformin is renally excreted, risk of lactate accumulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the dosing of metformin in renal impairment.

A

eGFR 45-59: 1500mg/d (divided doses)
eGFR 30-44: 1000mg/d (divided doses) check q3months
CI when eGFR <30ml/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are risk factors for lactic acidosis?

A

history of lactic acidosis
severe liver disease
alcohol abuse
radiologic problems
acute illness (severe infection, trauma)
severe dehydration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the MOA of sulfonylureas?

A

enhance secretion of insulin by binding to SU receptors on B cells of pancreas
-leads to closing of K+ channels and opening of Ca2+ channels
which stimulates insulin secretion
-they stimulate both basal and meal-stimulated insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are some sulfonylureas?

A

glyburide
gliclazide
glimepiride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the dosing of glyburide?

A

5-20mg/d (OD or BID)
usual dose is 5mg BID; may increase to 10mg BID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a CI of glyburide?

A

eGFR < 60ml/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the dosing of gliclazide?

A

gliclazide: 80-160mg (80mg OD or 80mg BID)
gliclazide MR: 30-120mg OD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is a caution of gliclazide? What about a CI?

A

caution in eGFR 30-60ml/min
CI in eGFR < 30 ml/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is something that can appear in the stool of a patient on gliclazide MR?

A

ghost shells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the dosing of glimepiride?

A

1-8mg/d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is a caution of glimepiride? What about a CI?

A

caution in eGFR 30-60ml/min
CI in eGFR < 30ml/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which sulfonylureas are on the formulary?

A

gliclazide MR and glyburide
regular release gliclazide and glimepiride are not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How are sulfonylureas best taken?
with food and in the AM
26
Describe the efficacy of sulfonylureas.
decrease A1C 1-1.5% (up to 2% in drug naive and elevated A1C) work quickly: can start titrating dose after 2wks based on fasting BG, then can titrate q1-2 weeks bang for buck at lower doses (effective at 1/2 max dose and max effective dose is 60-75% of max dose) better response if initiated early in diagnosis must adjust in renal impairment
27
What is the effect of sulfonylureas on CV outcomes?
neutral CV outcomes
28
What is the effect of sulfonylureas on CV outcomes?
neutral CV outcomes
29
What are side effects of sulfonylureas?
hypoglycemia (2-30%) -glyburide>glimepiride>gliclazide -glyburide on BEERS list (avoid in elderly) weight gain (~2kg) less frequent: nausea, rash, photosensitivity cross-sensitivity with sulfa allergy is rare
30
What are precautions/contraindications of sulfonylureas?
pregnancy/breast-feeding (all cross placenta except glyburide) CI in severe hepatic and renal impairment hold in acute illness
31
How are sulfonylureas metabolized?
metabolized in liver excreted in kidney
32
How are sulfonylureas handled in the elderly?
initiate at half normal dose and titrate up
33
What are drug interactions of sulfonylureas?
increased risk of hypoglycemia: -sulfonamides, salicylates, warfarin -alcohol -cimetidine, clarithromycin, fluconazole, NSAIDs, BB, MAOIs increased blood sugar: -phenytoin -rifampin -colesevelam (separate by 4hrs) -bosentan
34
What is the MOA of repaglinide?
binds to a site adjacent to the SU receptor, resulting in stimulation of the secretion of insulin from the pancreas -similar to SUs but faster onset and shorter D of A -peak levels within 1hr and half-life is 1hr
35
Describe the efficacy of repaglinide.
decreases A1C 1-1.5% works primarily to decrease PPG: it is intended to be taken before meals to improve early phase meal-induced insulin secretion
36
Describe the dosing of repaglinide.
A1C<8%: initiate at 0.5mg before each meal + titrate up A1C>8%: initiate at 1-2mg before each meal + titrate up max dose: 4mg before each meal (max dose 16mg/d) start at a low dose and titrate up q1-2 weeks until target BG achieved
37
How should repaglinide be administered?
right before a meal (within 30 minutes) due to short D of A -skip a meal, skip a dose -add a meal, add a dose
38
What is the eGFR that requires caution with repaglinide?
<30ml/min
39
What are the adverse effects of repaglinide?
hypoglycemia (more so when combined with other agents) weight gain (~0.3-1kg) *similar to SUs but to a lesser extent*
40
How is repaglinide metabolized? What is a precaution and CI?
in the liver by CYP 450 precaution with moderate hepatic impairment CI with severe liver disease
41
What are drug interactions of repaglinide?
increased repaglinide with: -3A4 inhibitors (cyclosporine, clarithromycin, grapefruit, azoles) -2C8 (gemfibrozil, clopidogrel; these are CI) decreased repaglinide with 3A4 inducers (carbamazepine, rifampin)
42
What is the MOA of acarbose?
inhibits a-glucosidase enzymes in the small intestine -these enzymes breakdown polysaccharides into absorbable glucose results in delay in rate of digestion of CHO and glucose absorption *net effect is reduction in PPG levels*
43
Describe the efficacy of acarbose.
decreases A1C 0.5-0.8% does not affect body weight or lipids
44
What is the dosing of acarbose?
initial 25-50mg OD, titrate up every couple of weeks to 50mg TID assess for efficacy q4-8wks to a max dose of 100mg TID take with the first bite of each meal
45
What are the adverse effects of acarbose?
GI -flatulence (40-80%) -diarrhea (30%) may elevate ALT: monitor LFTs first 6-12 months hypoglycemia: only negligible risk weight neutral
46
How should hypoglycemia be treated for a patient on acarbose?
glucose digestion of sucrose is impaired by acarbose
47
What are drug interactions with acarbose?
digestive enzyme preparations may decrease digoxin effect
48
What are cautions and CI of acarbose?
caution: GI conditions or IBD CI: eGFR <25ml/min and severe liver disease
49
What are the thiazolidinediones?
rosiglitazone pioglitazone
50
What is the MOA of thiazolidinediones?
bind to PPAR receptors which are primarily found in adipose tissue, activation alters genes that influence glucose and lipid metabolism enhance insulin sensitivity at muscle, liver, and fat tissues -they decrease insulin resistance decrease hepatic glucose production convert LDL particles to fluffy LDL that is less dense and less atherogenic
51
Describe the efficacy of thiazolidinediones.
decrease A1C 1-1.5% effect on TGs: PIO decreases by 10-20%, ROSI is neutral effects on LDL: ROSI increases LDL 5-15%, PIO is neutral effects on HDL: both may increase HDL to some degree
52
Describe the dosing of the thiazolidinediones.
rosi: initiate at 2-4mg OD; may increase to 4mg BID or 8mg OD pio: initiate at 15mg OD; titrate up 30-45mg OD have a delayed onset: wait 4-8wks for dose adjustments (max effect 3mo) larger people require a larger dose
53
What are cautions and CI of the thiazolidinediones?
caution in eGFR <60ml/min (no dose adjustment required) mainly metabolized by liver: -caution in severe liver disease
54
What is the EDS criteria of the thiazolidinediones?
must have tried a SU and metformin first
55
What are drug interactions of thiazolidinediones?
metabolized by CYP 2C8 -increased effects with inhibitors (gemfibrozil, TMP) -decreased effects with inducers (rifampicin)
56
What are the adverse effects of thiazolidinediones?
peripheral edema (~5%); combined with insulin (~15%) new onset/worsening of HF weight gain (2.5-4.8kg; dose related) increased distal fractures in postmenopausal women rare: -macular edema -anemia -pio: possible increased bladder cancer risk -rosi: possible increased MI risk
57
What is a CI of the thiazolidinediones?
heart failure
58
True or false: rosiglitazone has restricted access and informed consent is required
true
59
What must all diabetes medications show during trials due to the TZD data?
must show they are not bad for the heart
60
What are some GLP-1 agonists?
exenatide liraglutide dulaglutide (Trulicity) exenatide weekly lixisenatide semaglutide (Ozempic)
61
What are some DPP-4 inhibitors?
linagliptin (Trajenta) sitagliptin (Januvia) saxagliptin alogliptin
62
What are the drugs in Janumet?
sitagliptin and metformin
63
What are the incretin hormones?
GLP-1 and GIP -secreted from gut in response to ingestion of nutrients -augment insulin secretion -people with T2 have reduced incretin effect
64
What does activation of the GLP-1 receptor result in?
potent inhibition of gastric emptying potent inhibition of glucagon secretion reduction of food intake and body weight
65
What is the MOA of DPP4-inhibitors?
block the enzyme DPP4 which rapidly hydrolyzes incretins, thus enhancing the action of endogenous incretins -as a result they increase insulin release and decrease glucagon in a dose-dependent manner
66
Describe the efficacy of DPP4 inhibitors.
decrease A1C ~0.7% (ranges, but typically ~1%) work quickly-can see effects within weeks
67
Which DPP4 inhibitor is not EDS? What is the EDS criteria of DPP4 inhibitors?
alogliptin those uncontrolled after metformin and a SU
68
What are the adverse effects of DPP4 inhibitors?
overall, well tolerated (no hypo on their own, weight neutral) more common: headache, nasopharyngitis, URTI less common/rare: -hypersensitivity -bullous pemphigoid -joint pain -pancreatitis
69
What are some drug interactions with DPP4 inhibitors?
combined with insulin or SU-->risk of hypoglycemia saxagliptin: clearance is reduced/enhanced with 3A4 inhibitors and inducers linagliptin: clearance enhanced with strong 3A4 inducers all: avoid with GLP1A (similar MOA and risk of pancreatitis)
70
What are the results of DPP4 inhibitors and CV safety?
safe but not cardioprotective
71
Why are DPP4 inhibitors a good option for the elderly?
weight neutral to modest weight loss low risk of hypo well tolerated OD no titration less A1C lowering than other antihyperglycemics
72
Which GLP1RAs are covered under EDS? What are their EDS criterias?
lixisenatide: tx of T2 combined with a basal insulin when control is not adequate with a SU and metformin semaglutide: tx of T2 when combined with metformin and a SU when control is not adequate with a SU and metformin
73
What is the MOA of GLP1RAs?
stimulate insulin secretion in a glucose-dependent manner -decreased glucagon -slow gastric emptying -increase satiety -decreased hepatic glucose production
74
How should GLP1RAs be stored when not in use? What about when in use?
not in use: fridge in use: room temp or fridge (oral semaglutide: room temp)
75
What do you do if you miss a dose of a short-acting GLP1RA?
exenatide: skip lixisenatide: within the hour prior to the next meal
76
What is the dosing of long-acting GLP1RAs?
liraglutide: 0.6mg OD x 1 week, then 1.2-1.8mg OD exenatide QW: 2mg SC q week dulaglutide: 0.75mg SC weekly; can increase to 1.5mg q week semaglutide: 0.25mg SC weekly; increase to 0.5mg after 4 weeks then 1mg
77
What do you do if you miss a dose of a long-acting GLP1RA?
administer ASAP if at least 3 days until next dose -5 days for semaglutide
78
How is oral semaglutide dosed?
3mg OD for 30 days increase to 7mg OD for at least 30 days may increase 14mg OD *empty stomach after waking up, with sip of water, wait 30 minutes before eating/drinking/other meds*
79
How is oral semaglutide formulated?
to make po bioavailable, it is co-formulated with SNAC this creates a bubble around it and prevents degradation from stomach acid so it can be absorbed -1% makes the journey -keep in original packaging
80
What do you do if you miss a dose of oral semaglutide?
skip and take the next day
81
Describe the efficacy of GLP1RAs.
decreases A1C 1-1.5% -semaglutide SC appears to be more potent than dulaglutide long-acting GLPs more potent than short-acting work on both FPG and PPG, however, short-acting GLPs have more effect on PPG, & long-acting have more effect on FPG modest decrease in bp (within 3 weeks) *benefits on BG are dose-dependent*
82
What are common adverse effects of GLP1RAs?
GI: N/V/D (up to 40%); especially nausea (20-50%) -nausea and vomiting are generally mild and transient and resolve after 4-8 weeks (longer with exenatide BID and lixisenatide)
83
How can you minimize nausea with GLP1RAs?
appreciate the feeling of fullness: stop eating when full eat smaller portions and eat slowly titrate slowly; stay on low dose until nausea improves avoid fatty, spicy, and high-fibre foods consider using on an empty stomach-dont administer close to a large meal consider end of day dosing stay hydrated and drink cold water when nauseous
84
What are the effects of GLP1RAs on weight & hypoglycemia?
weight loss -varies but on average ~3kg -not due to N/V/D -weight loss is dose dependent and will plateau low risk of hypoglycemia -when initiating may either stop or decrease dose of SU and perhaps decrease insulin dose
85
What are drug interactions with GLP1RAs?
these drugs decrease gastric emptying, space out drugs that require rapid GI absorption (>1hr before GLP1RA): -oral contraceptives -antibiotics -narrow TI drugs -increases levothyroxine by 33%
86
What are contraindications of GLR1RAs?
family history of MTC (medullary thyroid cancer) or MEN2 family history of pancreatic cancer
87
How do GLP1RAs exert cardioprotective and renal benefits?
effects on BP, LDL/TG (although modest) effects on weight effects on BG may help modulate vascular inflammation (inhibit atherogenesis) *combination of metabolic, CV, and anti-inflammatory effects*
88
True or false: lixisenatide, semaglutide po, and exenatide have not been shown to be CV protective but are CV safe
true the trials for CV protective were done on liraglutide, semaglutide sc, and dulaglutide
89
What are the CV outcomes with repaglinide?
absence of CV outcome data
90
What are rare adverse effects of GLP1RAs?
acute gallstone disease acute pancreatitis increased cancer risk retinopathy

PHAR152 (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions