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PHAR 152 > Diabetes - Part 4 > Flashcards

Diabetes - Part 4 Flashcards

1
Q

What does core management consist of for T2DM?

A

Self-management
Lifestyle modifications
Pharmacotherapy

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2
Q

What is the MOA of Metformin?

A

Decrease hepatic glucose production
Can also enhance sensitivity to insulin
Increases glucose utilization via action in the gut

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3
Q

What is the dosing for Metformin?

A

Start slow: initiate at 250-500mg OD
Titrate up by 500mg weekly if no GI side effects
Desired usual dose: 850-1000mg BID
Max dose: 850 TID
Adjust in renal failure

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4
Q

What is the efficacy for Metformin?

A

Decrease A1C 1-1.5% (up to 2% with A1C of 9%
Also decreases TG and LDL 8-15%, and slightly increases HDL by 2%

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5
Q

What drug interactions does Metformin have?

A

Cimetidine: increases Metformin levels by 60%
Dolutegravir: can increase Metformin concentration
Alcohol: potentiates Metformin effect on lactate metabolism; enhanced hypoglycemia effect
Contrast media: hold for 48 hours after imaging

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6
Q

What are the adverse effects of Metformin?

A

Common: GI
Less common: metallic taste, vit B12 deficiency with long term use
Very low risk of hypo when used as monotherapy
Weight neutral to modest weight loss

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7
Q

What precautions should be taken for Metformin?

A

Watching for lactic acidosis
If someone has reduced eGFR there will be reduced elimination and therefore a concern for accumulation of lactate

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8
Q

What is the dosing of Metformin for renal impairment?

A

Decrease dose if ClCr <60ml/min
EGFR 45-59: 1500mg/d (divided doses)
EGFR 30-44: 1000mg/d (divided doses)
CI when eGFR < 30ml/min

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9
Q

What are the risk factors for lactic acidosis?

A

History of lactic acidosis
Severe liver disease
Alcohol abuse
Radiologic procedures
Acute illness
Server dehydration

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10
Q

What is the MOA of sulfonylureas(SUs)?

A

They enhance the secretion of insulin by binding to SU receptors on the beta cells of the pancreas
This leads to closing of K+ channels and opening of calcium channels which stimulates insulin secretion
They stimulate both basal and meal-stimulated insulin release

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11
Q

What are the SUs?

A

2nd gen: glyburide, gliclazide, glimepiride

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12
Q

What is the dosing for glyburide?

A

5-20mg/d (OD or BID)
Usual dose is 5mg BID; may increase to 10 BID
CI in eGFR < 60ml/min

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13
Q

What is the dosing for gliclazide?

A

80-160mg (80mg OD or 80mg BID)
Gliclazide MR 30-120mg OD
Caution in eGRF 30-60ml/min
CI in eGFR <30ml/min

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14
Q

Which SUs are on the formulary?

A

Glyburide and gliclazide MR

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15
Q

Directions for SUs:

A

Take with food
Take in am
Start at lower doses and increase pm

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16
Q

What is the efficacy of SUs?

A

Decrease A1C 1-1.5% (up to 2% in elevated A1C)
Effective at 1/2 max dose
May get a better response if initiated early in diagnosis; long-term durability is poor
Must dose adjust in renal impairment

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17
Q

What are the adverse effects of SUs?

A

Hypoglycemia (2-30%)
- higher incidence with glyburide > glimepiride > gliclazide
Weight gain (~2kg)
Less frequent: nausea, skin reaction

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18
Q

What are the precautions for SUs?

A

Pregnancy/breast-feeding (would only use glyburide)
CI in severe hepatic and renal impairment
Hold in acute illness

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19
Q

What are drug interactions do SUs have?

A

Sulfonamides, salicylates, warfarin
Alcohol
Cimetidine, clarithromycin, fluconazole, NSAIDs, beta-blockers, MAOIs
These drugs may increase risk of hypo
~
Phenytoin
Rifampin
Colesevelam
These drugs may lessen effect and increase blood sugar

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20
Q

What is the meglitinide drug?

A

Repaglinide

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21
Q

What is the MOA of repaglinide?

A

Binds to a side adjacent to the SU receptor, resulting in stimulation of the secretion of insulin from the pancreas
Similar to SUs but have faster onset and shorter D of A
Peak levels within 1 hour

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22
Q

What is the efficacy of repaglinide?

A

Decrease A1C 1-1.5%
Works primarily to decrease PPG: is intended to be taken before meals or improve early phase meal-induces insulin secretion

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23
Q

What is the dosing for repaglinide?

A

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 (16mg/d)
Start at a low dose and titrate up every 1-2 weeks until target BG achieved
Needs to be administered right before a meal

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24
Q

What are the adverse effects of repaglinide?

A

Hypoglycemia (more so when combined with other agents)
Weight gain (~0.3-1kg)

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25
What are the precaution for repaglinide?
Metabolized in the liver. Clearance significantly reduced in hepatic impairment. Precaution worn moderate hepatic impairment and CI with severe liver disease. Use caution if eGFR <30ml/min
26
What drug interactions does repaglinide have?
Increased repaglinide with: - 3A4 inhibitors (cyclosporine, clarithromycin, grapefruit, azoles) - 2C8 (gemfibrozil, clopidogrel; these are CI) Decreased repaglinide with 3A4 inducers (carbamazepine, rifampin)
27
What is the alpha-glucosidase inhibitors?
Acarbose
28
What is the MOA of Acarbose?
Alpha-glucosidase enzymes in the small intestine are responsible for the breakdown of polysaccharides into absorbable glucose. Acarbose inhibits these enzymes, hence there is a delay in the rate of digestion of CHOs and glucose absorption NET EFFECT IS REDUCTION OF PPG LEVELS
29
What is the efficacy of Acarbose?
Decrease A1C 0.5-0.8% (less then the others) Does not affect body weight or lipids
30
What is the dosing for Acarbose?
Initial: 25-50mg OD titrate up every couple of weeks to 50mg TID Max dose of 100mg TID Take with the first bite of each main meal
31
What are the adverse effects of Acarbose?
GI: flatulence (40-80%), diarrhea (30%), bloating, abdominal pain May elevate ALT Hypoglycemia Weight neutral
32
What drug interactions does Acarbose have?
Digestive enzyme preparations May decrease digoxin effect
33
What are the precautions for Acarbose?
Those with IBD or GI conditions CI if eGFR < 25ml/min and severe liver disease
34
What are the thiazolidinediones?
Rosiglitazone and pioglitazone
35
What is the MOA of thiazolidinediones?
Bind to PPAR-y 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 TISSUE - decreases insulin resistance Insulin sensitizers
36
What is the efficacy of thiazolidinediones?
Decrease A1C by 1-1.5%
37
What is the dosing for Rosiglitazone?
Initiate at 2-4mg OD; may increase to 4mg BID or 8mg OD (greater effects seen BID) Larger people will generally require larger doses Have delayed onset: wait 4-8 weeks for dose adjustments
38
What is the dosing for pioglitazone?
Initiate at 15mg OD; titrate up to 30-45mg OD Larger people will generally require larger doses Have delayed onset: wait 4-8 weeks for dose adjustments
39
What are the precautions for thiazolidinediones?
Caution in eGFR <60ml/min Mainly metabolized by liver: use with caution or use an alternative in severe liver disease
40
What must you have tried to get a thiazolidinedione in SK?
They are both EDS so must have tried a SU and Metformin first
41
What are the drug interactions for thiazolidinediones?
Metabolized by CYP 2C8: - increased effects with inhibitors (gemfibrizol, TMP) - decreased effects with inducers (rifampicin)
42
What are the adverse effects of thiazolidinediones?
Peripheral edema(~5%); combined with insulin (~15%) New-onset/worsening of HF Weight gain (2.5-8.8kg; dose related) Increase distal fractures in post menopausal women CI in heart failure
43
T or F: TZDs are good fro CV safety
False. They are controversial
44
What are the incretin-based therapies?
GLP-1 receptor agonists DPP-4 inhibitors
45
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
46
What is the MOA of DPP-4 inhibitors?
Block the enzyme DPP-4 which rapidly hydrolysis incretins, thus enhancing the action of endogenous incretins As a result they increase insulin release and decrease glucagon in a dose dependent manner
47
What is the efficacy of DPP-4 inhibitors?
Decrease A1C by ~0.7% (ranges, but typically < 1%) Work quickly - can see effects within a couple weeks
48
How can you get a DPP-4 inhibitor?
Uncontrolled after Metformin and a SU
49
What are the generic DPP-4 inhibitors?
Sitagliptin & saxagliptin
50
What is the dosing for DPP4 inhibitors?
Sitagliptin 100mg OD Saxagliptin 5mg OD Linagliptin 5mg OD Alogliptin 25mg OD
51
How should DPP4 doses be adjusted for renal dosing?
Sitagliptin: eGFR 30-44 50mg OD, eGFR<30 25mg OD Saxagliptin: eFGR 30-44 2.5mg OD, eGFR<30 2.5mg OD with caution(avoid in ESRD, dialysis) Linagliptin: no dose adjustment Alogliptin: eGFR 30-44 12.5mg OD, eGFR<30 6.25mg OD
52
What are the adverse effects of DPP4i?
Overall, well tolerated medications No hypo on their own Weight neutral More common: headache, nasopharyngitis, URTI Less common: hypersensitivity reactions, joint pain, pancreatitis
53
What are the drug interactions of DPP4i?
Increase risk of hypo when combined with SU or insulin Avoid with GLP1RA: similar MOA and increased risk of pancreatitis
54
Are DPP4i cardioprotective?
No but they are CV safe
55
What is the cost for GLP1RAs?
>$200/month
56
What is semaglutide (ozempic)?
A GLP1RA
57
Which GLP1RAs are covered under SK formulary?
Lixisenatide and semaglutide
58
When can someone get semaglutide?
For treatment of T2 when combined with Metformin and a SU when control is not adequate with a SU and Metformin
59
When can someone get lixisenatide?
For treatment of T2 combined with a basal insulin when control is not adequate with a SU and Metformin
60
What is the MOA of GLP1RA?
Stimulate insulin secretion in a glucose-dependent manner; decrease glucagon, slow gastric emptying, increase satiety
61
What is the dosing for exenatide?
Short acting 5ug BID sc x 1 month, then 10ug BID Within 60 minutes prior to am and pm meals (meals must be at least 6 hours apart)
62
What is the dosing for lixisenatide?
Short acting 10ug od sc x 14 days, them 20ug OD - take within 1 hour prior to the first main meal of the day
63
What is the dosing for liraglutide?
Long acting - can take at anytime 0.6mg OD x 1 week, then 1.2mg to 1.8mg daily
64
What is the dosing for exenatide?
2mg sc q week
65
What is the dosing for dulaglutide?
0.75mg sc weekly; can increase to 1.5mg q week
66
What is the dosing for semaglutide?
0.25mg sc weekly; increase to 0.5mg after 4 weeks then 1mg
67
If you miss a weekly dose for a long acting GLP1RA how long do you have to retake it?
Admitted ASAP if at least 3 days until next dose (dulaglutide and exenatide) and if at least 5 days for semaglutide
68
What is the dosing for oral semaglutide?
Start with 3mg OD for 30 days Increase to 7mg OD for at least 30 days May increase to 14mg OD
69
How is oral semaglutide to be taken?
Take on empty stomach after waking up Take with a sip of water (<120ml) Wait at least 30 minutes before eating, drinking, or taking other oral medications
70
What do you do if you miss a dose of oral semaglutide?
Skip and take the next day
71
Which GLP1RA should you take caution with when eGFR < 15?
Dulaglutide Liraglutide Semaglutide SC
72
When should caution be taken with semaglutide po?
When eGFR <30
73
Which GLP1RAs are not recommended for eGFR<30 and caution in 30-50?
Exenatide QW and exenatide Lixisenatide just not recommended for eGFR<30
74
What is the efficacy of GLP1RAs?
Decrease A1C by about 1-1.5% Benefits are dose dependent Long acting GLPs are more potent then short acting Modest decrease in BP(within 3 weeks)
75
Short acting GLPs have more effect on _____ and long acting have more effect on ____.
PPG, FPG
76
What are the common adverse effects of GLP1RAs?
GI: N/V/D(up to 40%); especially nausea (20-50%) Less common: injection site reactions, increased HR Rare: acute gallstone disease, retinopathy, acute pancreatitis??
77
What are the affects on weight for GLP1RAs?
Cause wight loss - on average ~3kg
78
What is the affect on hypoglycemia for GLP1RAs?
Low risk of hypo
79
What drug interactions doo GLP1RAs have?
Since they decrease gastric emptying they need to be spaced out more then an hour from drugs that require rapid GI absorption: - oral contraceptives - antibiotics - narrow TI drugs - increase levothyroxine by 33%

PHAR 152 (10 decks)

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