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Therapeutics II > Noninsulin agents > Flashcards

Noninsulin agents Flashcards

1
Q

Oral agents

A

-metformin
-SGLT-2
-GLP-1
-DPP-4
-Sulfonylureas
-TZDs

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2
Q

Injectable agents

A

-GLP-1
-GIP and GLP-1

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3
Q

Person centered approach

A

-glycemic goals
-weight goals
-hypoglycemic risk (older peep)
-history of CVD/KD
-med cost

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4
Q

Metformin (Glucophage) MOA

A

-dec hepatic glucose production
-inc intestinal glucose utilization
-can inc GLP-1 secretion
-modest effect on inc tissue uptake and use by muscle

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5
Q

Metformin clinical applications

A

-adjunct to diet in t2dm
-combo
-consider for use in all t2dm

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6
Q

Why metformin recommended in t2dm

A

-reduce CVD rrisk
-extensive experience
-efficacious w minimal hypoglycemia
-positive/weight neutral effects
-cost effective

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7
Q

Off label indications metformin

A

-t1dm who are overweight w low ketoacidosis risk
-PCOS to lower androgen/inc ovulation

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8
Q

Overall efficacy metformin

A

-A1c 1.5-2%
-FBG: 60-80mg dec

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9
Q

Metformin excretion

A

-urine
-kidney function

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10
Q

Metformin advantages

A

-low hypoglycemia risk
-low lipids (LDL, TG)
-inc fibrinolysis = CV protection
-dec macrovasc probs
-dec stroke risk
-dec diabetic deaths

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11
Q

metformin disadvantages

A

-risk factor for fatal lactic acidosis (rare)
-GI side effects
-Vit B13 deficiency
-dementia risk

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12
Q

Risk factors of lactic acidosis in metformin use

A

-renal dysfunction (use eGFR not SCr)
-HF
-alcoholics
-shock
-COPD
-hepatic failure
-surgery/contrast dye

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13
Q

metformin and surgery

A

-hold metformin 1-2 days before and then around 2 days after depending upon pt status

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14
Q

Metformin GI effects

A

-30-50% pt
-diarrhea/flatulence
-N/V
-take w largest meal of the day
-titrate dosage

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15
Q

Vit B12 deficiency + metformin

A

-can worsen neuropathy
-monitor/provide supplementation
-check annually esp in pt w anemias and/or neuropathy

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16
Q

Risk of dementia w metformin

A

-controversial
-some say it does some say it doesn’t

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17
Q

Metformin dosing

A

-initial 500mg BID or 850mg qd wf
-titrate weekly and inc dose by 250-500mg

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18
Q

max dose of metformin

A

-2g/day actual
-2.5g/day according to package inserts

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19
Q

Metformin dosage forms

A

-500mg, 850mg, 1000mg

-SustainedActing formulation back (less GI effects) (recalled in 2020 bc NDMA levels that inc cancer and liver damage)

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20
Q

metformin and eGFR > 60

A

-no contraindication
-monitor SCr annually

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21
Q

metformin and 45 < eGFR < 60

A

-dafe
-continue use
-monitor SCr 3-6 month

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22
Q

metfromin and 30 < eGFR < 45

A

-not recommended
-recude dose by 50% if already taking
-monitor SCr q3months

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23
Q

metformin and eGFR < 3o

A

-do NOT start
-STOP if taking

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24
Q

SGLT2

A

-major transporter of renal glucose
-inhibition allows renal glucose excretion
-pissing sugar

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25
Q

SGLT-2 uses

A

-adjuct to diet/exercise t2dm
-recommended +/- metformin as initial therapy

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26
Q

SGLT-2 also good for pt w

A

-ASCVD or high risk
-HF
-CKD

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27
Q

SGLT efficacy

A

-A1c: 0.5-1%
-FBG: 25-35mg
-PPG: 40-60
-weight: 1-5kg
-x: dec

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28
Q

SGLT adverse effects

A

-UTI
-genital micotic infections
-inc urination

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29
Q

UTI from SGLT

A

-53% inc risk of UTI in t2dm in general
-not contraindicated in asx bacteruria
-pt w lots of UTIs should be seen for risk factors
-consider SLGT if pt UTI free for year

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30
Q

Genital mycotic infections (SGLT)

A

-already 81% inc risk in t2dm
-counsel on s/s and hygiene
-d/c in life threatening infections

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31
Q

FDA warning for serious genital infections

A

-necrotizinf faciitis of perimeum (Fournier’s gangrene)
-need abx and surgery
-seek med attention (tenderness, swelling, fever)

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32
Q

SLGT2 and urination

A

-pt w bladder probs not gonna want it
-AM dosing

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33
Q

other adverse effects SGLT2

A

-hypotension due to osmotic diuresis (worse on diuretics)
-hyperkalemia (rare)
-inc cholesterol
-DKA FDA warning

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34
Q

DKA risk and SGLT

A

-t2dm w mild elevated BG
-euglycemic
-illness, dec food/water intake, dec insulin dose, alcohol
-dont give to t1dm

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35
Q

DKA recommendations w SGLT

A

-hold 3 days before surgery (4 if ertugliflozin)
-restart once oral intake back to baseline
-wait until risk factors resolve
-discuss sick day rules

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36
Q

SGLT FDA warning

A

-DKA
-bone fracures + dec BMD
-AKI
-amputation risk

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37
Q

SGLT and bone fractures (canagliflozin)

A

-canagliflozin
-loss of BMD at spine and hip
-other flozins fine
-caution hypotension as fall risk

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38
Q

SGLT and AKI (canagliflozin and dapagliflozin)

A

-50% cases start within one month of starting tx
-pt improve after d/c
-volume depletion and hypotension likely causes

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39
Q

SGLT cautions

A

-dehydration or hypotension risk (diuretics, NSAIDs, ACEI/ARBs)

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40
Q

SGLT and amputation

A

-canagliflozin
-toes
-weigh risk v benefits
-monitor pain sores
-risk factors: amputations, PVD, neuropathy, foot ulcers

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41
Q

SGLT drugs

A

-Canagliflozin
-Dapagliflozin
-Empagliflozin
-Ertugliflozin

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42
Q

Canagliflozin dosing

A

-100mg qd
-max 300mg
-max 100mg if eGFR 30-60 and no signs of albuminuria
-or <30 may use if albuminuria >300 but don’t start

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43
Q

SGLT2 contraindication

A

-end stage renal failure on HD
-not gonna d/c until they are on dialysis tho
-use in pt w eGFR>20

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44
Q

Dapagliflozin dosing

A

-5mg
-10 max

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45
Q

Empagliflozin dosing

A

-10mg
-max25

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46
Q

Ertugliflozin dosing

A

-5mg qd
-max 15

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47
Q

SGLT2 counseling

A

-stay hydrated
-monitor renal function
-suspend use during acute illlness or planned surgery (3days (4 on ertugliglozin))

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48
Q

SGLT2 CV benefits

A

-better on outcome, hospitilizations
-good for renal protection
-starting to be used outside of diabetes (HF and CKD)

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49
Q

GLP-1 drugs

A

-Liraglutide
-Dulaglutide
-Semaglutide
-Exenatide
-Lixisenatide

50
Q

GLP1s

A

-stimulate B-cell growth
-inhibit B-cell death
-short acting
-inhibit glucagon
-delays emptying (slow absorption)
-dec appetite
-highly resistant to DPP-IV
-inc first and second-phase insulin secretion
-GLUCOSE DEPENDENT (insulin only released w BG) less risk of hypoglycemia

51
Q

Clinical applications of GLP-1

A

-intial therapy +/- metformin
-preferred to insulin in t2dm
-if insulin used, combo w GLP1 for better efficacy

52
Q

GLP1 efficacy

A

-A1c more effective than SGLT2
-short-acting = PPG control
-long-acting = FBG control
-weight loss UP

53
Q

GLP1 excretion

A

-short acting GLP-1 eliminated by kidneyss

54
Q

GLP-1 contraindication

A

-severe renal disease
-pancreatitis (TG>300)
-thyroid cancer

55
Q

GLP1 adverse effects

A

-dose dependent nausea
-V/D
-dose titration dec sx and will improve over couple weeks
-acute pancreatitis
-inc risk of thyroid tumors
-gall bladder disease
-Gastroparesis (avoid)
-Retinopathy

56
Q

gall bladder disease from GLP-1

A

-esp high dose and long term use
-inc risk of gallstones, inflammation, biliary sludge
-use caution/avoid in preexisting gallbladder disease
-consider d/c if gallbladder probs
-prevent w low fat diet, hydration, activity

57
Q

Gallstones (cholelithiasis)

A

-cholestero or bilirubin stones
-can block flow of bile = pain, infection, inflammation
-may alter bile composition
-rapid weight loss = rapid mobilization of cholesterol from adipose tissue during weight loss into bile

58
Q

gallbladder disease

A

-ab pain (right upper quadrant)
-N/V
-fever
-use GLP w ca

59
Q

Retinopathy in GLP-1

A

-caused by rapid drop in A1c
-CAUTION pt w nonproliferative retinopathy
-AVOID in proliferative diabetic retinopathy

60
Q

Dulaglutide (trulicity) dosing

A

-0.75-4.5mg
-qweek
-do NOT use in ESRD
-needles included

61
Q

Semaglutide (Ozempic) dosing

A

-0.25 x 4 weeks then 0.5mg-2mg
-qweek
-needles included

62
Q

Liraglutide (victoza) dosing

A

-0.6mg x 7 days the 1.2-1.8mg
-qd

63
Q

Exenatide (Byetta) dosing

A

-5mcg x month then 10 mcg
-BID
-avoid if CrCl<30

64
Q

Lixisenatide (Adylyxin) dosing

A

-10mcg x 14 fays then 20mcg
-avoid eGFR< 15
-qd

65
Q

Dulaglutide (trulicity) counseling

A

-admin in thigh, ab, arm
-single dose pens
-remove cap, press pen aginst skin and press button
-good for needlephobes

66
Q

Semaglutide (ozempic) counseling

A

-admin thigh, ab, arm
-store pens in fridge
-can store 56 days at room temp
-check flow every pen

67
Q

Liraglutide (victoza) counseling

A

-give any time of day independent of meals
-admin in thigh, ab, arm
-pre-filled pens

68
Q

Oral semaglutide (rybelsus)

A

-3mg PO x 30 days then inc 7mg qd
-inc 14mg if needed
-can change to 7mg if on 0.5mg SQ
-take 30 min before first food or other oral meds with no more than 4 oz water (vomiting)

69
Q

GLP1 benefits

A

-CVD and renal

70
Q

dual GIP/GLP1

A

-Tirzepatide (Mounjaro)

71
Q

Tirzapatide (mounjaro)

A

-enhance both phase insulin secretion
-reduce glucagon levels in glucose-dependent manner
-delay gastric emptying
-inc satiety

72
Q

Tirzepatide (Mounjaro) efficacy

A

-A1c: 1.5-2.3 close to metformin
-FBG: 40-60
-weight loss 6-11kg

73
Q

tirzepatide adverse effects

A

-similar to GLPs
-N/V/D
-pancreatitis, thyroid tumors, gallbladder disease
-tachycardia

74
Q

Tirzepatide dosing

A

-2.5mg SQ weekly
-adjust qmonth by 2.5mg/week
-up to 15mg weekly

75
Q

DPP-4 inhibitors

A

-Sitagliptin (Januvia)
-Saxagliptin (Onglyza)
-Linagliptin (Tradjenta)
-Alogliptin (Nesina)

-not as strong efficacy
-weight neutral
-renal dosing

76
Q

DPP-4 adverse effects

A

-nasopharygitis
-upper RTI
-headaches
-pancreatitis
-joint pain
-HF risk (sitagliptin fine tho)

77
Q

which DPP-4 for HF

A

-sitagliptin

78
Q

Whidh DPP-4 not renally eliminated

A

-linagliptin
-no dose adjustment required

79
Q

Sitagliptin dosing

A

-100mg CrCl >50
-50 mg CrCl 30-50
-25mg for CrCl <30 or HD

80
Q

Saxagliptin dosing

A

-2.5-5mg qd
-2.5mg for CrCl <50

81
Q

Linagliptin

A

-5 mg qd
-no renal dose adjustment

82
Q

Alogliptin

A

-25mg qd CrCl > 50
-12.5mg CrCl 30-50
-6.25mg CrCl < 30 or HD

83
Q

Sulfonylureas moa

A

-stimulate insulin release from B cells
-may inc binding between insulin and receptors or inc amt of receptors
-glucose independent tho (hypoglycemia)

84
Q

Sulfonylurea clinical application

A

-adjuct diet/exercise t2dm
-combo w insulin and non insulin
-CHEAP

85
Q

Sulfonylurea efficacy

A

-A1c: dec 1-2%
-FBG dec 60-70

86
Q

2nd gen sulfonylureas

A

-Glipizide*
-Glyburide
-Glimepiride

-we dont use 1st gen

87
Q

Sulfoynlurea kinetics

A

-glyburide and glipizide more effective when taken 30 min BEFORE meal
-metabolized by liver
-excreted in urine
-glipizide metabolized w/o formation of active metabolites = better in renal disease

88
Q

sulfonylurea preferred in renal disease

A

-glipizide
-no formation of active metabolites
-good for elderly too

89
Q

Sulfonylureas adverse effects

A

-hypoglycemia
-weight gain
-hematologic
-allergy (steven johnsons)(sulfa)

90
Q

hypoglycemia + sulfonylurea risk

A

-renal/hepatic probs
-elderly or malnourished
-other hypoglycemic drugs

91
Q

sulfonylurea hematologic adverse effects

A

-leukopenia
-thrombocytopenia
-aplastic anemia

-sulfa component

92
Q

sulfonylurea dosing

A

-start low and slow esp in old ppl
-inc dose every 1-2 weeks until max
-max dose inc side effects w no benefit

93
Q

sulfonylurea max dosing

A

-about 60-75% of current max dose listed
-glipizide might actually be 20mg

94
Q

Glipizide dose

A

-start 2.5-5mg qd
-max 40mg (20mg for XL)

95
Q

Glyburide dose

A

-start 1.25-5mg qd
-max 20mg

96
Q

Glyburide micronized dose

A

-start 1.5-3mg qd
-max 12mg

97
Q

Sulfonylurea population cautions

A

-elderly
-renal/hepatic disease
-irregular dietary intake
-alcoholics
-with hypoglycemic agents

-all inc risk of hypoglycemia

98
Q

Sulfonylurea best candidates

A

-type 2 only
-short duration of diabetes (newly diagnosed)
-FBS < 250mg/dL
-high fasting C-peptide levels

99
Q

Sulfonylurea treatment failure

A

-25% primary failure
-after 5 years, 50-75% secondary failure
-common failure after 612 months

100
Q

Thiazolidinediones (TZDs) MOA

A

-bind to peroxisome proliferator activator receptor y on fat cells and vascular cells (PPAR-y)
-improve cell response to insulin w/o inc secretion
-dec insulin resistance
-dec hepatic glucose production

101
Q

other benefits of TZDs

A

-Pioglitazone can dec TG by 10-20%
-LDL unchanged w Pioglitazone but maybe inc w rosiglitazone (converts LDL to large fluffy ones?)
-inc HDL 3-9 mg/dL
-inc endothelial function
-slight dec in BP

102
Q

TZD efficacy

A

-dec A1c 0.5-1.5%
-FBG dec 60-70
-dependent on insulinemia

103
Q

TZD adverse effects

A

-Hepatotoxicity
-resume ovulation (good in PCOS tho)
-exacerbations of HF
-macular edema
-inc fracture risk 25%

104
Q

TZD hepatotxicity

A

-check baseline LFTs
-do NOT start is LFTs > 2.5x nl
-check LFTs periodically
-d/c if LFTs > 3x normal
-monitor N/v, ab pain, fatigue, anorexia, urine

105
Q

TZD monitoring

A

-LFTs > 3x = d/c
-N/V
-ab pain
-fatigue
-anorexia
-dark urine

106
Q

TZD and HF

A

-caution in pt w NYHA class 3-4 HF
-inc edema
-inc weight

107
Q

which TZD we using

A

-pioglitazone

108
Q

Pioglitazone (TZD) dosing

A

-start 15-30mg qd
-max 30-45mg
-inc dose every 12 WEEKS

109
Q

Tx principles for T2DM

A

-treat aggressively to achieve goals
-start diet/exercise
-consider metformin and combo therapy
-consider weight

110
Q

considerations for T2DM tx

A

-disease states
-BG and A1c
-HYPOglycemia risk
-SE
-impact on weight
-cost and other pt factors

111
Q

T2DM tx in ASCVD, HF, CKD

A

-SGLT2is and GLP1s

112
Q

When to start dual therapy T2DM

A

-A1c > 1.5-2% above goal
-or A1c > 7.5-9%

-at least 8.5% get them on 2

113
Q

Insulin tx for T2DM

A

-prefer GLP1 when possible
-use insulin if:
-weight loss
-hyperglycemia signs
-A1c > 10%
-BG> 300mg/dL

-recommend BASAL insulin combo therapy w GLP1
-go to basal-bolus insulin for tighter control if no GLP1

-be aware of overbasalization

-additional therapy if goals not reached after 3 months

114
Q

Overbasalization

A

-if basal dose is 0.5units/kg/day or high variability in BG readings
-evaluate basal level and consider basal-bolus

115
Q

1st line for T2DM w ASCVD

A

-GLP1 or SGLT2

116
Q

1st line in pt w HF

A

-SGLT2

117
Q

1st line in pt w CKD

A

-SGLT2
-GLP1 if not

118
Q

Efficacy considerations

A

-Metformin
-consider combo
-avoid risk of HYPOglycemia when necessary

119
Q

Tx for pt that need to minimize weight gain

A

-GLP1 or SGLT2

120
Q

Rx to avoid in pt that need to minimize weight gain

A

-sulfonylureas
-meglitinides
-TZDs

121
Q

Cost considerations

A

-cheaper: sulfonylureas and TZDs

122
Q

drug chart

A

drug chart

Therapeutics II (55 decks)

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