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Therapeutics II > Anti-hyperlipidemics > Flashcards

Anti-hyperlipidemics Flashcards

1
Q

Dyslipidemia risks

A

-coronary, cerebrovasc, peripheral arterial disease
-major risk for CHD
-coronary artherosclerosis contributes to ischemic heart disease

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2
Q

Lipids

A

-cholesterol
-cholesterol esters
-TGs
-phospholipids

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3
Q

Lipoproteins

A

-LDL
-HDL
-VLDL

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4
Q

Apolipoproteins

A

-Apo-B
-Apo-A1
-Apo-CIII

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5
Q

Artherosclerosis pathogenesis

A
  1. endothelial injury
  2. inflammatory response
  3. Macrophage infiltration
  4. Platelet adhesion
  5. Smooth muscle cell proliferation
  6. Extracellular matrix accumulation
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6
Q

Dyslipidemia sx

A

-MOST ASYMPTOMATIC
-depends on severity and duration of disease
-chest pain
-palpitations
-sweating
-anxiety
-SOB
-loss of consciousness
-difficulty w speech or movement
-ab paain
-sudden death

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7
Q

Signs of dyslipidemia

A

-pancreatitis
-eruptive xanthomas
-peripheral polyneuropathy
-inc BO
-waist size (>40 inches men >35 women)
-BMI >30kg/m

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8
Q

Dyslipidemia lab values

A

-inc Non HDL-C, TC, LDL-C
-inc TGs, APO-B, CRP, LDL-P
-DEC HDL

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9
Q

LDL-C

A

-amount of cholesterol in LDL particles

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10
Q

LDL-P

A

-number of LDL particles
-not routinely ordered

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11
Q

Non HDL-C

A

-amount of cholesterol in atherogenic particles
-not routine
-non-HDL-C = TC- HDL

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12
Q

Apo-B

A

-number of artherogenic particles
-not routine

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13
Q

ApoB, LDL-P, non HDL-C

A

-all valid in non-fasting sample w elevated TGs
-all mosre predictive of future CVD risk than LDL-C alone

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14
Q

Non-fasting lipid profile appropriate if:

A

-assessing initial risk
-pt not on lipid therapy
-no family hx of genetic hyperlipidemia
-pt TGs low

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15
Q

Fasting Lipid Panel (FLP)

A

-TC
-TG
-HDL-C
-LDL-C (friedewald equation)

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16
Q

Friedewald equation

A

-estimate LDL from FLP
-LDL calculation not valid when TG >400
-LDL = TC - HDL - TG/5

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17
Q

What else is important w a FLP

A

-Non-fasting sample (TC, HDL)
-TC/HDL (goal <5:1, optimal 3-3.5:1)

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18
Q

pracice FLP

A

practice FLP

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19
Q

Nonpharma tx

A

-DASH diet (veggiess, fruit, grain, fish, legumes, oils, nuts)
-reduce calories from saturated and trans fats (5-6% of calories)
-lower sodium intake to at least 1000mg/day
-exercise 90-150min/week

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20
Q

Saturated Fat intake calculation

A

-9 cal per gram of fat
-19g fat *9 = 171 cal
-171/2000 = 8.6%
-double quarter pounder w cheese
-goal 5-6%

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21
Q

Olestra to Reduce intake of saturated fats and cholesterol

A

-nondigestable, nonabsorbable, noncaloric fat substitute

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22
Q

Soluble fiber

A

-oat bran
-pectins or gums
-psyllium products
-binds cholesterol in gut and reduces hepatic production and clearance
-psyllium seed 10-15g daily may dec TC and LDL by 20%

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23
Q

Psyllium products

A

-binds cholesterol in gut and reduces hepatic production and clearnace
-psyllium seed 10-15g daily may dec TC and LDL by 20%

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24
Q

Lifestyle change

A

-Olestra
-soluble fiber
-plant stanols and sterols
-weight reduction (10% loss if overweight)
-inc physical activity 40 min daily 3-4 days a week
-smoking cessations

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25
Q

Omega-3 Fatty Acids

A

-eating fish once weekly can reduce CV risk
-EPA/DHA
-reduces TG
-may increase LDL 4-49%
-most products OTC
-Lovaza
-Vascepa

-harder to stop bleeding (SSRIs too)
-NOT GOOD FOR AFIB

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26
Q

Lovaza

A

-2-4g qd or divided BID
-omega-3

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27
Q

Vascepa

A

-2g BID wf
-omega-3
-icosapent ethyl (IPE): the only triglyceride
-risk-based nonstatin therapy FDA-approved for ASCVD risk reduction

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28
Q

Effects of non-pharma therapy

A

-reducing saturated fat and adding 2g plant sterols great

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29
Q

Pharmacologic treatment options

A

-HMG-CoA reductase inhibitors (statins)
-Bile acid resins/sequestrants
-Niacin
-Cholesterol absorption inhibitor
-fibrates
-PCSK9 inhibitors/monoclonal antibodies
-Inclisiran
-Bempedoic acid

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30
Q

Pharma agents that have more effect on TGs

A

-fibrates
-omega-3

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31
Q

HMG-CoA reductase inhibitors

A

-lovastatin (altoprev, mevacor)
-pravastatin (pracachol)
-pitavastatin (livalo)
-simvastatin (Zocor)
-fluvastatin (lescol
-atorvastatin (lipitor)
-Rosuvastatin (crestor)

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32
Q

Low intensity statins + doses

A

-simvastatin 10mg
-pravastatin 10-20mg
-lovastatin 20mg
-fluvastatin 20-40mg

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33
Q

Moderate intensity statins

A

-atorvastatin 10-20mg
-rosuvastatin 5-10mg
-simvastatin 20-40mg
-pravastatin 40-80mg
-lovastatin 40-80mg
-fluvastatin 40mg BID
-fluvastatin XL 80mg
-pitavastatin 1-4mg

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34
Q

High intensity statins**

A

-atorvastatin 40-80mg
-rosuvastatin 20-40mg

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35
Q

Fluvastatin (lescol) properties

A

-CYP2C9
-lipophillic
-minimal effect on food absorption
-admin IR in evening, XR whenever

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36
Q

Pitavastatin properties

A

-CYP2C9,2C8
-lipohillic
-dec food absorption
-admin whenever

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37
Q

Pravastatin properties

A

-hydrophillic
-dec food absorption
-admin whenever

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38
Q

Lovastatin properties

A

-CYP3A4
-lipophillic
-inc food absorption
-IR evening, XR any time

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39
Q

Simvastatin properties

A

-CYP3A4,3A5
-lipophillic
-no effect on food
-take whenever

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40
Q

-Atorvastatin properties

A

-CYP3A4
-lipophillic
-no effect on food
-take anytime

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41
Q

Rosuvastatin properties

A

-CYP2C9
-hydrophillic
-no effect on food
-take anytime

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42
Q

Lipophillic statins

A

-fluvastatin
-pitavastatin
-lovastatin
-simvastatin
-atorvastatin

-more likely for muscle pain

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43
Q

hydrophillic statins

A

-pravastatin
-rosuvastatin

-inc risk of liver toxicity

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44
Q

statins w CYP3A4 interactions

A

-lovastatin
-simvastatin
-atorvastatin

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45
Q

When to take simvastatin

A

-evening

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46
Q

simvastatin 80mg

A

-lets not use that in practice
-inc adverse effects

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47
Q

Statin considerations

A

-well tolerated
-LFT
-muscle toxicity (myopathy/rhabdomyolysis)
-muscle pain
-dark urine
-avoid lots of grapefruit juice
-AVOID in pregnancy and ppl that might get pregnant

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48
Q

Statin LFT monitoring

A

-obtain LFT at baseline
-repeat if clinically indicated
-dc if LFTs 3x upper limit of normal
-LFT in the 1000s

49
Q

Statin adverse effects

A

-impaired renal/hepatic function
-prior statin intolerance
-muscle disorders
-unexplained ALT elevations >3 x normal (1000s)
-other drugs
-over 75 years old

50
Q

What to do when pt experiences muscle symtpom/fatigue

A

-dc statin and evaluate for rhabdomylosis
-evaluate exacerbating conditions
-restart or lower dose once sx resolve

-most times go from lipophilic to hydrophillic

51
Q

statin contraindications

A

-liver disease
-elevated transaminases
-preg/breastfeeding

52
Q

statin and muscle injury incidence

A

-not that high tbh
-check CK >10x upper limit, dc statin
-might need to switch to non CYP3A4
-one glass of grapefruit juice prob not gonna effect anything tho
-consider CoQ10 150-200mg qd prior to statin rechallenge and during therapy

53
Q

statin muscle injury management

A

-assess if exercise related
-dc and see if resolves
-switch to hydrophillic statin
-change dose
-consider other agents

54
Q

Statin alt dosing strategy

A

-every other day or once weekly can help and dec cost
-double daily dose if every other day

55
Q

Simvastatin contraindications*

A

-itraconazole
-ketoconazole
-posaconazole
-erythromycin
-clarithromycin
-telithromycin
-HIV protease inhibitors
-nefazodone
-gemfibrozil
-cyclosporine
-danazol

->10mg: verapamil and diltiazem
->20mg: amiodarone, amlodipine, ranolazine

56
Q

statins and hyperglycemia

A

-start statin anyway
-be aware of hyperglycemia risks

57
Q

statin monitoring

A

-FLP at baseline
-FLP 4-12 wekks after initiation
-FLP 3-12 months as indicated

-consider CK if risk of muscle probs
-CK if muscle sx
-hepatic function in s/sx hepatotoxicity

58
Q

Bile Acid Resins (BARs) drugs

A

-cholestyramine (questran, prevalite)
-Colestipol (colestid)
-Colesevelam (welchol)

59
Q

Bile Acid Resin mech

A

-cation exchange resins
-traps bile and excretes it
-no bile = body makes more bile using cholesterol

60
Q

BAR disadvantages

A

-may inc TGs
-take other meds 1 hour before or 4 hours after

61
Q

BAR adverse effects

A

-GI (Nausea, constipation, flatuelence, bloating)
-impaired absorption of fat soluble vitamins (ADEK)
-hypernatremia
-hyperchoresmia
-GI obstruction

62
Q

BAR might dec activity of

A

-acetaminophen
-TZDs
-warfarin*
-digoxin*
-contraceptives
-steroids
-ezetimibe
-fibrates
-thiazide diuretics

63
Q

BAR contraindications

A

-cholestyramine: bilary obstruction

-colesevelam: hx bowel obstruction, TGs >500 or hx of hyperTG-induced pancreatitis

64
Q

Niacin

A

-OTC
-CV benefits
-not regulated well
-hepatotoxicity risk

65
Q

Niacin flushing

A

-prostaglandin
-admin ASA 325mg 30 min before niacin
-take closer to meals
-avoid alc
-start lower doses
-inc LFTs
-hyperuricemia and hyperglycemia
-may inc levels of statins

66
Q

Niacin contraindications

A

-hepatic disease
-transaminase elevations
-peptic ulcer
-arterial hemorrhage

67
Q

Ezetimibe (Zetia) mech

A

-cholesterol absorption inhibitor
-combo w simvastatin = Vytorin
-can dec LDL 12-20% more as combo

68
Q

Exetimibe adverse effects

A

-fatigue
-diarrhea
-GI upset

-well tolerated

69
Q

Ezetimibe contraindications

A

-use w statin and active hepatic disease or transaminase elevations
-preg/breastfeeding

70
Q

Fibrate drugs

A

-fib

-more for TG instead of LDL

71
Q

fibrate side effects

A

-GI
-rash
-myalgia
-dizziness

72
Q

fibrate contraindications

A

-hx gallbladder
-ERSD or dialysis
-persistent liver disease

73
Q

fibrates inc levels of

A

-statins (dont give both)
-ezetimibe
-sulfonylureas
-warfarin

74
Q

PCSK9 monoclonal antibody drugs

A

-Alirocumab (praluent)
-Evolocumab (repatha)

75
Q

PCSK9 mech

A

-inhibits PSCK9 binding to LDL receptors and upregulate recycling of LDL receptors
-43-64% reduction in LDL

76
Q

PSCK9 indication

A

-adj to diet and statin
-HeFH or ASCVD

77
Q

PSCK9 adverse effects

A

-GI upset
-inc LFTs
-inj site reaction
-myalgia
-influenza

78
Q

PCSK9 consider for:

A

-stable and progressive ASCVD
-high risk/statin intolerant
-smth else

79
Q

Inclisiran (Leqvio)

A

-dec LDL and cholesterol
-inj
-approved for adults only (unlike PCSK9)

80
Q

Inclisiran indication

A

-adj to diet
-HeFH or ASCVD

81
Q

Inclisiran mech

A

-siRNA
-inhibits translocation of PCSK9 inhibiting PCSK9 production
-prolongs activity of LDL receptors

82
Q

Inclisiran adverse effects

A

-inj site rx
-arthralgia
-UTI
-diarrhea
-bronchitis
-pain in extremities
-dyspnea

83
Q

Inclisiran dosing

A

-initial dose + one at 3 months
-then twice a year

84
Q

Bempedoic Acid (nexletol) use

A

-not seen
-adj to diet and statin
-reduce LDL in HeFH or ASCVD

85
Q

Bempedoic acid adverse reaction

A

-URTI
-muscle spasms
-hyperuricemia
-back/ab pain
-bronchitis
-anemia
-elevated liver enzymes

86
Q

Bempedoic acid cautions

A

-may inc blood uric acid levels and lead to gout
-risk tendon rupture
-avoid use w simvastatin > 20mg and pravastatin >40mg (myopathy)

87
Q

Bempedoic trials

A

-reduce risk of MI

88
Q

Red yeast rice

A

-lovastatin ingredient
-shown to lower TC LDL TG
-maybe inc HDL
-same effects/interaction as statins
-no regulation or guidelines for use

89
Q

Lomitapide (Juxtapid)

A

-HoFH
-only available through REMS
-boxed warning for hepatotoxicity

90
Q

Evinacumab (Evkeeza)

A

-mab for HoFH
-IV infusion q4weeks

91
Q

Guideline risk groups

A

-clinical ASCVD (cardiovasc event)
-diabetes 45-75y/o
-LDL>190
-over 75y/o
-ASCVD risk >20%

92
Q

Primary prevention groups

A

-pt w no ASCVD event
-hypercholesterolemia
-DM
-over 75

93
Q

primary prevention if LDL-C >190mg

A

-no risk assessment
-high intensity statin (class I)
-moderate if over 75

94
Q

primary prevention in DM age 40-75

A

-moderate intensity statin
-risk assessment to consider high-intensity

95
Q

age >75 primary prevention

A

-clinical assessment
-discuss risks
-moderate dont really go high

96
Q

primary prevention in ASCVD >20% under 75 y/o

A

-always high intensity

97
Q

guideline slide

A
98
Q

risk enhancing factors for primary prevention

A

-fam hx of premature ASCVD
-LDL > 160 constitently
-CKD
-TG > 175
-pre-eclampsia
-premature menopause
-inflammatory disease
-ethnicity
-metabolic syndrome
-ApoB,CRP,Lp labs high
-decreased ankle-brachial index

99
Q

Secondary prevention eligibility

A

-past ASCVD event
-MI
-angina (stable or unstable)
-revascularization
-stroke (TIA)
-Peripheral Artery Disease (incl aortic aneurysm)

100
Q

Secondary prevention

A

-always high intensity statin
-mod if over 75

-add zetia if too high
-then go PSCK9 inhibitor

101
Q

Patients benefiting from statin

A

-clinical ASCVD at any age
-LDLC>190
-40-75 w DM or ASCVD risk
-fam hx
-risk discussion everyone else

102
Q

Statin monitoring

A

-initiate statin
-follow up 4-12 weeks until dose stable
-follow up every 3-12 months

103
Q

Coronary Artery Calcium test (CAC)

A

-not used often
-measures calcium buildup
-use if risk decision still unclear to use statin
-CAC=0: assess other risks
-CAC=1-99: FAVORS statin therapy esp over 55y/o
-CAC>100: initiate at least mod statin

104
Q

patient groups considered for non-statin therapy

A

-under 75 on statin for seconday prevention
-over 21 on statin for primary prevention
-40-75 w DM for primary prevention

105
Q

when to treat non-statin for secondary prevention under 75

A

-w or w/o additional risk factors
-LDL-C threshold of 70mg/dl on max statin
-consider PSCK9 if veery high risk and LDL not at goal

106
Q

when to treat non-statin over 21 for primary prevention

A

-baseline LDL>190 no underlying causes
-add ezetimibe if reduction <50% or LDL > 100

107
Q

when to treat non-statin age 40-75 w DM for primary prevention

A

-risk assessment
-ezetimibe if ASCVD risk >20% on max statin

108
Q

non-statin recommendations after max statin

A
  1. ezetimibe if LDL not at goal or pt w DM w ASCVD risk >20%
  2. PSCK9 inhibitors consider if LDL not at goal or if pt cannot tolerate statin/ezetimibe
    other: BAS if <50% reduction in LDL on max statin + ezetimibe and TG>300
109
Q

Treatment goals

A

-treat to target
-primary: LDL < 100
-secondary: LDL<70

-or max tolerated for ease

110
Q

should tx be expanded?

A

-meds dont reverse damage
-may be beneficial to use in younger adults
-still being looked at for long-term efficacy

111
Q

Hypertriglyceridemia categories

A

-persistent
-moderate (150-499)
-severe (>500)

-pt w DM have hyperTGs w high A1c (turns extra sugar into TGs)

112
Q

persistent hyper TG

A

-fasting TG >150 after 4-12 weeks lifestyle intervention, stable dose of max statin, and secondary cause evaluation

113
Q

moderate hyper TG

A

-excess TGs carried in VLDL
-150-499

114
Q

Severe hyperTG

A

> 500
-excess TGs in VLDLs
-elevated chylomicrons inc pancreatitis risk
-high pancreatitis risk

115
Q

HyperTG treatment

A

-give statin

116
Q

Secondary TG factors

A

-obesity
-metabolic syndrom
-alc use
-DM
-HYPOthyroidism
-liver/kidney disease
-meds (slide102)

117
Q

lifestyle mods to tx hyperTGs

A

-5-10% weight loss = 20% dec in TG
-low fat diet
-restrict alc, sugar, refined carbs
-physical activity

118
Q

Pharma tx of hyperTGs

A

-use statin
-adults 40-75 w mod-severe TGs and ASCVD risk >7.5% = statin
-add fibrate OR omega-3 FA in severe esp if TGs>1000 and max out statin (vascepa or lovazza first)

119
Q

patient cases

A

Therapeutics II (55 decks)

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