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PHRM 844 > Lecture 13 > Flashcards

Lecture 13 Flashcards

1
Q

Non-Insulin Treatments

  • none of these products are as effective as ___ in terms of glucose lowering effect
  • ideal treatments would ___ beta cell function, prevent weight ___ , prevent ____ , and improve/not worsen concomitant disease states
A
  • insulin
  • preserve, gain, hypoglycemia
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2
Q

Metformin

MOA:
- decrease ___ glucose production
- increase ___ glucose utilization and decrease glucose uptake into ___
- increase ___ secretion
- modest effect on increasing ___ uptake and utilization of glucose by the ___

Glucophage, Fortamet, or Glumetza

A
  • hepatic
  • intestinal, circulation
  • GLP-1
  • tissue, muscle
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3
Q

Metformin

Clinical applications
- adjunct to diet in uncontrolled type ___ pts
- in combination with insulin and non-insulin agents
- reduce __ death
- minimal ___
- ___ neutral

Off label:
- overweight type ___ with low risk of ___
- PCOS (lowers ___ and increase ___ )

A
  • type 2
  • CV
  • hypoglycemia
  • weight
  • type I, ketoacidosis
  • androgen, ovulation
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4
Q

metformin PK

T or F: metformin is excreted, changed in the urine

A

F: unchanged

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5
Q

metformin

Efficacy
- decrease A1C by ___ %
- decrease FBG by ___ mg/dL
- no weight gain and often weight loss ( ___ kg )

A

1.5-2%
60-80 mg/dL
2-3 kg

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6
Q

Metfomrin

Advantages
- less risk for ___ due to no insulin release
- deceased lipids ( ___ and ___ ) by ___ %
- ___ loss/neutral
- cost effective
- increased ___ = CV protection
- decrease ___ complications and total mortality
- decrease risk of ___ compared to insulin and SUs
- decrease diabetes related death and ___

A
  • hypoglycemia
  • TG, LDL, 8-15%
  • weight
  • fibrinolysis
  • macrovascular
  • stroke
  • MI
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7
Q

Metformin

Disadvantages
- may cause ___ (rare, weak causal relationship)
- ___ side effects
- ___ deficiency
- ___ risk (controversial)

A
  • lactic acidosis
  • GI
  • Vit B12
  • dementia
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8
Q

Metformin

Contraindications
- renal dysfunction (look at ___ , not SCr)
- unstable ___
- alcoholics
- pts at risk for ___ acidosis (post ___ , ___ failure, COPD, shock, and contrast ___ )

A
  • eGFR
  • HF
  • lactic, MI, hepatic, dye
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9
Q

T or F: metformin has shown some benefit in stable HF patients

A

T; decreased mortality, decrease HF, may be from effect on decreasing insulin resistance

contraindicated in pts with unstable HF

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10
Q

Metformin Dosing - initial and max dose

initial - ___ mg po BID or ___ daily, with meals
- titrate dose ___ or bi-monthly by ___ - ___ mg/day

Max: ___ gm/day
- package insert says ___ gm/day

A

500, 850
- weekly, 250-500

2
- 2.55

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11
Q

Metformin Dosing - renal insufficiency

eGFR , 60-45
- safe to start therapy
- continue to use is already taking
- monitor SCr every ___ months

A

3-6 months

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12
Q

Metformin Dosing - renal insufficiency

eGFR 44-30
- starting metformin is ___ recommeded
- reduce dose by ____ % if already taking
- monitor SCr every ___ months

A
  • NOT
  • 50%
  • 3 months
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13
Q

Metformin Dosing - renal insufficiency

eGFR < 30
- ___ start metformin
- ___ metformin if currently takig

A
  • DO NOT
  • STOP
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14
Q

SGLT2 - MOA

  • SGLT2 is the major renal transporter for ___ reabsorption
  • inhibition of SGLT2 leads to renal glucose ____ (up to ___ gm/day)
A
  • glucose
  • excretion, 60-90

pee out extra sugar

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15
Q

SGLT2

clinical application
- adjunct to diet and exercise in type ___ pts
- recommended with or without ___ as apropriate ____ therapy for individuals with type ___ diabetes at high risk for ACVD, ___ , and/or ___

A
  • 2
  • metformin, initial, 2
  • HF, CKD
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16
Q

SGLT2 - Efficacy

A1C: decrease ___ - ___ %
FBG: decrease ___ - ___ mg/dL
PPG: decrease ___ - ___ mg/dL
weight: decrease ___ - ___ kg
BP: decrease SBP ___ - ___ mmHg and DBP: ___ - ___ mmHg

A
  • 0.5-1.0%
  • 25-35 mg/dL
  • 40-60 mg/dL
  • 1-5 kg
  • 3-6, 2-3
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17
Q

SGLT2 - PK

  • undergoes ___ by UGT1A9 and UGT2B4 to ___ metabolites
  • ___ metabolism is minimal
  • excreted mostly in ____ , but 1/3 in urine
A
  • glucuronidation
  • inactive
  • CYP3A4
  • feces
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18
Q

SGLT2

Adverse effects
- UTIs
- ___ infections
- increased ___
- ___ due to volume loss
- hyper___
- ___ cholesterol

A
  • fungal (yeast)
  • urination
  • hypotension
  • kalemia
  • increased
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19
Q

SGLT2

FDA warning: DKA
- most pts were type ___ with mildly elevated ___
- factors: illness, dehydration, decreased insulin dose
- hold SGLT2 ___ days before surgery, resume when oral intake is back to normal baseline
- hold 4 days before surgery for ___

A
  • 2, BG
  • 3
  • ertugliflozin
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20
Q

SGLT2

FDA warning: bone fractures and decreased BMD with ___

A

canagliflozin

21
Q

SGLT2

FDA warning: AKI with ___ and ___
- 50% of cases started within one month of treatment initiation and improved after treatment discontinuation
- likely due to volume ___and ___
- caution in pts with potential for ___ or if they are on ____ , NSAIDs, or ___ / ___

A

canagliflozin, dapagliflozin
- depletion, hypotension
- dehydration, diuretics, ACE-Is/ARBs

22
Q

SGLT2

FDA warning: increased leg and foot amputations with ___
- mostly affecting the ___
- use caution with pts with prior amputation, PVD, ___, and foot __

warning removed in 2020

A

canagliflozin
- toes
- neuropathy, ulcers

23
Q

SGLT2

FDA warning: serious genital infections
- necrotizing fascitis of perineum ( ___ gangrene)
- urologic emergency, requires ___ antibiotics and immediate ___ intervention
- pts should seek medical attention if there is amy tenderness, redness, swelling, fever, fatigue, and malaise

A
  • Fournier’s
  • broad-spectrum, surgical
24
Q

T or F: we can use SGLT2s on dialysis pts to improve kidney function

A

FALSE

they cannot pee bro

25
Q

SGLT2 renal dosing - canagliflozin

eGFR > 60
- ___ mg daily, MAX: ___ mg daily

eGFR 30-60
- MAX: ___ mg daily if no ___

eGFR < 30
- do not start
- if already taking, may use ___ mg daily if albuminurial > ___ mg/dL

A
  • 100, 300
  • 100, albuminuria
  • 100, 300
26
Q

SGLT2 renal dosing - dapagliflozin

eGFR > 45
- ___ mg daily, MAX: ___ daily

eGFR < 25
- do not start
- if on therapy, ___ and monitor

A
  • 5, 10
  • continue
27
Q

SGLT2 renal dosing - empagliflozin

eGFR > 30
- ___ mg daily, MAX: ___ daily

eGFR < 30
- do not start
- if on therapy, ___ and monitor

A
  • 10, 25
  • continue
28
Q

SGLT2 renal dosing - ertugliflozin

eGFR > 60
- ___ mg daily, MAX: ___ mg daily

eGFR < 45
- do not start
- if on therapy, monitor
- if eGFR persistently low, ___

A

5, 15
discontinue

29
Q

SGLT2 CV Benefits

CV benefits may be from a combination of decreased ___ , decreased ___ , and osmotic diuresis leading to a reduction in ___ volume

A

weight
BP
plasma

30
Q

SGLT2 Renal Benefits

reduce worsening renal function, end stage renal disease or renal death by ___ %
- benefits seen in pts with/without ___
- benefits independent of improvement in ___ control

A
  • 45%
  • atherosclerosis
  • glycemic
31
Q

GLP-1 Agonists

MOA:
GLP-1 potentiates glucose-___ insulin secretion by stimulating ___ growth and differentiation and insulin gene expression
- inhibit ___ death
- inhibits ___ secretion, delays ___ emptying, and decreases ___
- resistant to ___
- increases ___ and ___ phase insulin secretion after ___ occur
- leads to insulin release only in presence of elevated ___

A

dependent, B-cell
- B-cell
- glucagon, gastric, appetite
- DPP-V
- 1st, 2nd, meals
- BG

32
Q

GLP-1 Agonists

clinical applications:
- recommended with or without ___ as appropriate ___ therapy for individuals with type II with high ACVD, HF, and/or CKD
- for type II preferred over ___ if possible
- if ___ is used, combo therapy with GLP-1 is recommended for greater efficacy and durability of.
- choose insulin first when A1C is > ___ %

A
  • metformin, initial
  • insulin
  • insulin
  • 10%
33
Q

GLP-1 Agonists - Efficacy

A1C: decrease ___ - ___ %
Weight: decrease ___ - ___ kg, may be up to ___ kg depending on dosing

A
  • 0.7-1.6%
  • 1.5-3 kg, 6 kg
34
Q

GLP-1 Agonists

SE:
- nausea, vomiting, diarrhea
- acute ___
- black box warning for ___ cancer
- ___ disease
- avoid in pts with ___
- retinopathy

A
  • pancreatitis
  • thyroid
  • gall bladder
  • gastroparesis
35
Q

GLP-1 Agonists

  • short acting GLP-1s ( ___ and ___ ) have more effect on ___
  • long acting have more effect on ___
A
  • exenatide, lixisenatide, PPG
  • FBG
36
Q

GLP-1 Agonists

T or F: long acting GLP-1s are eliminated by the kindeys and are contraindicated with severe renal disease

A

F; short acting

37
Q

dulaglutide (Trulicity)

  • frequency: once ___
  • dosing: ___ mg up to ___ mg
  • use in caution in ___
  • needles included? ___
  • available in ___ pens
  • at ___ click, medication has been administered, you can remove pen
A
  • weekly
  • 0.75, 4.5
  • ESRD
  • yes, attached
  • single
  • 2nd
38
Q

semaglutide (Ozempic)

  • frequency: once ___
  • dosing: ___ mg x ___ weeks, then ___ mg up to ___ mg
  • needles included? ___
  • after 1st use, pen can be stored at ___ days at room temp/fridge
  • check ___ with each new pen
  • during injection, push button until dose counter goes back to ___ and count to ___ seconds before removing the pen
A
  • weekly
  • 0.25mg , 4 weeks, 0.5 mg, 2 mg
  • yes, in carton
  • 56
  • flow
  • 0, 6
39
Q

liraglutide (Victoza)

  • frequency: once ___
  • dosing: ___ mg x ___ days, then ___ mg up to ___ mg
  • needles included? ___
  • available in prefilled pens with ___ mg per pen
  • discard unused medication after ___ days
  • only prime prior to ___ injection
  • limited experience in ___
A
  • daily
  • 0.6 mg, 7 days, 1.2 mg, 1.8 mg
  • no
  • 18
  • 30 days
  • 1st
  • ESRD
40
Q

exenatide (Byetta)

  • frequency: ___
  • dosing: ___ mcg x 1 ___, then ___ mcg
  • avoid if CrCl < ___
  • needles included? ___
A
  • BID
  • 5 mcg, month, 10 mcg
  • 30
  • no
41
Q

exenatide (Bydureon Bcise)

  • frequency: once ___
  • dosing: ___ mg
  • avoid if CrCl < ___
  • needles included? ___
A
  • once weekly
  • 2 mg
  • 30
  • yes
42
Q

lixisenatide (Adylyxin)

  • frequency: once ___
  • dosing: ___ mcg x ___ days, then ___ mcg
  • avoid if eGFR < ___
  • needles included?
A
  • daily
  • 10 mcg, 14 days, 20 mcg
  • 15
  • no
43
Q

semaglutide (Rybelsus)

  • ___ mg po daily x ___ days, then increase to __ mg daily
  • can increase to ___ mg daily if needed
  • take ___ min before first food/beverage/other oral medications with no more than ___ oz plain water
A
  • 3 mg, 30 days, 7 mg
  • 14 mg
  • 30 min, 4 oz
44
Q

T or F: GLP-1s have CV and renal benefit

A

True

REWIND, SUSTAIN-6, LEADER

45
Q

Dual GLP-1 and GIP - tirzepatide (Mounjaro)

MOA:
- enhances ___ and ___ phase insulin sectrion
- reduces ___ levels, in a glucose - ___ manner
- delays ___ emptying
- decreases ___
- ___ outcomes expected 2025
- marketed especially for ___

A
  • 1st, 2nd
  • glucagon, dependent
  • gastric
  • appetite
  • CV
  • weight loss
46
Q

Dual GLP-1 and GIP - tirzepatide (Mounjaro)

Efficacy
A1C: decrease ___ - ___ %
FBG: decrease ___ - ___ mg/dL
PPG: decrease ___ - ___ mg/dL
Weight: decrease ___ - ___ kg

A
  • 1.5-2.3 %
  • 40-60 mg/dL
  • 20-40 mg/dL
  • 6-11 kg
47
Q

Dual GLP-1 and GIP - tirzepatide (Mounjaro)

Adverse Effects
- N, V, D
- acute ___
- ___ tumors
- ___ disease
- ___ cardia (10-20% of pts)

A
  • pancreatitis
  • thyroid
  • gall bladder
  • tachycardia
48
Q

Dual GLP-1 and GIP - tirzepatide (Mounjaro)

Dosing
- ___ mg once ___
- adjust once a month by ___ mg per ___ increments, up to ___ mg

A
  • 2.5 mg, weekly
  • 2.5 mg, week
  • 15 mg

PHRM 844 (52 decks)

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