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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
Omega-3 Fatty Acids
-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
26
Lovaza
-2-4g qd or divided BID -omega-3
27
Vascepa
-2g BID wf -omega-3 -icosapent ethyl (IPE): the only triglyceride -risk-based nonstatin therapy FDA-approved for ASCVD risk reduction
28
Effects of non-pharma therapy
-reducing saturated fat and adding 2g plant sterols great
29
Pharmacologic treatment options
-HMG-CoA reductase inhibitors (statins) -Bile acid resins/sequestrants -Niacin -Cholesterol absorption inhibitor -fibrates -PCSK9 inhibitors/monoclonal antibodies -Inclisiran -Bempedoic acid
30
Pharma agents that have more effect on TGs
-fibrates -omega-3
31
HMG-CoA reductase inhibitors
-lovastatin (altoprev, mevacor) -pravastatin (pracachol) -pitavastatin (livalo) -simvastatin (Zocor) -fluvastatin (lescol -atorvastatin (lipitor) -Rosuvastatin (crestor)
32
Low intensity statins + doses
-simvastatin 10mg -pravastatin 10-20mg -lovastatin 20mg -fluvastatin 20-40mg
33
Moderate intensity statins
-atorvastatin 10-20mg -rosuvastatin 5-10mg -simvastatin 20-40mg -pravastatin 40-80mg -lovastatin 40-80mg -fluvastatin 40mg BID -fluvastatin XL 80mg -pitavastatin 1-4mg
34
High intensity statins**
-atorvastatin 40-80mg -rosuvastatin 20-40mg
35
Fluvastatin (lescol) properties
-CYP2C9 -lipophillic -minimal effect on food absorption -admin IR in evening, XR whenever
36
Pitavastatin properties
-CYP2C9,2C8 -lipohillic -dec food absorption -admin whenever
37
Pravastatin properties
-hydrophillic -dec food absorption -admin whenever
38
Lovastatin properties
-CYP3A4 -lipophillic -inc food absorption -IR evening, XR any time
39
Simvastatin properties
-CYP3A4,3A5 -lipophillic -no effect on food -take whenever
40
-Atorvastatin properties
-CYP3A4 -lipophillic -no effect on food -take anytime
41
Rosuvastatin properties
-CYP2C9 -hydrophillic -no effect on food -take anytime
42
Lipophillic statins
-fluvastatin -pitavastatin -lovastatin -simvastatin -atorvastatin -more likely for muscle pain
43
hydrophillic statins
-pravastatin -rosuvastatin -inc risk of liver toxicity
44
statins w CYP3A4 interactions
-lovastatin -simvastatin -atorvastatin
45
When to take simvastatin
-evening
46
simvastatin 80mg
-lets not use that in practice -inc adverse effects
47
Statin considerations
-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
48
Statin LFT monitoring
-obtain LFT at baseline -repeat if clinically indicated -dc if LFTs 3x upper limit of normal -LFT in the 1000s
49
Statin adverse effects
-impaired renal/hepatic function -prior statin intolerance -muscle disorders -unexplained ALT elevations >3 x normal (1000s) -other drugs -over 75 years old
50
What to do when pt experiences muscle symtpom/fatigue
-dc statin and evaluate for rhabdomylosis -evaluate exacerbating conditions -restart or lower dose once sx resolve -most times go from lipophilic to hydrophillic
51
statin contraindications
-liver disease -elevated transaminases -preg/breastfeeding
52
statin and muscle injury incidence
-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
statin muscle injury management
-assess if exercise related -dc and see if resolves -switch to hydrophillic statin -change dose -consider other agents
54
Statin alt dosing strategy
-every other day or once weekly can help and dec cost -double daily dose if every other day
55
Simvastatin contraindications*
-itraconazole -ketoconazole -posaconazole -erythromycin -clarithromycin -telithromycin -HIV protease inhibitors -nefazodone -gemfibrozil -cyclosporine -danazol ->10mg: verapamil and diltiazem ->20mg: amiodarone, amlodipine, ranolazine
56
statins and hyperglycemia
-start statin anyway -be aware of hyperglycemia risks
57
statin monitoring
-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
Bile Acid Resins (BARs) drugs
-cholestyramine (questran, prevalite) -Colestipol (colestid) -Colesevelam (welchol)
59
Bile Acid Resin mech
-cation exchange resins -traps bile and excretes it -no bile = body makes more bile using cholesterol
60
BAR disadvantages
-may inc TGs -take other meds 1 hour before or 4 hours after
61
BAR adverse effects
-GI (Nausea, constipation, flatuelence, bloating) -impaired absorption of fat soluble vitamins (ADEK) -hypernatremia -hyperchoresmia -GI obstruction
62
BAR might dec activity of
-acetaminophen -TZDs -warfarin* -digoxin* -contraceptives -steroids -ezetimibe -fibrates -thiazide diuretics
63
BAR contraindications
-cholestyramine: bilary obstruction -colesevelam: hx bowel obstruction, TGs >500 or hx of hyperTG-induced pancreatitis
64
Niacin
-OTC -CV benefits -not regulated well -hepatotoxicity risk
65
Niacin flushing
-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
Niacin contraindications
-hepatic disease -transaminase elevations -peptic ulcer -arterial hemorrhage
67
Ezetimibe (Zetia) mech
-cholesterol absorption inhibitor -combo w simvastatin = Vytorin -can dec LDL 12-20% more as combo
68
Exetimibe adverse effects
-fatigue -diarrhea -GI upset -well tolerated
69
Ezetimibe contraindications
-use w statin and active hepatic disease or transaminase elevations -preg/breastfeeding
70
Fibrate drugs
-fib -more for TG instead of LDL
71
fibrate side effects
-GI -rash -myalgia -dizziness
72
fibrate contraindications
-hx gallbladder -ERSD or dialysis -persistent liver disease
73
fibrates inc levels of
-statins (dont give both) -ezetimibe -sulfonylureas -warfarin
74
PCSK9 monoclonal antibody drugs
-Alirocumab (praluent) -Evolocumab (repatha)
75
PCSK9 mech
-inhibits PSCK9 binding to LDL receptors and upregulate recycling of LDL receptors -43-64% reduction in LDL
76
PSCK9 indication
-adj to diet and statin -HeFH or ASCVD
77
PSCK9 adverse effects
-GI upset -inc LFTs -inj site reaction -myalgia -influenza
78
PCSK9 consider for:
-stable and progressive ASCVD -high risk/statin intolerant -smth else
79
Inclisiran (Leqvio)
-dec LDL and cholesterol -inj -approved for adults only (unlike PCSK9)
80
Inclisiran indication
-adj to diet -HeFH or ASCVD
81
Inclisiran mech
-siRNA -inhibits translocation of PCSK9 inhibiting PCSK9 production -prolongs activity of LDL receptors
82
Inclisiran adverse effects
-inj site rx -arthralgia -UTI -diarrhea -bronchitis -pain in extremities -dyspnea
83
Inclisiran dosing
-initial dose + one at 3 months -then twice a year
84
Bempedoic Acid (nexletol) use
-not seen -adj to diet and statin -reduce LDL in HeFH or ASCVD
85
Bempedoic acid adverse reaction
-URTI -muscle spasms -hyperuricemia -back/ab pain -bronchitis -anemia -elevated liver enzymes
86
Bempedoic acid cautions
-may inc blood uric acid levels and lead to gout -risk tendon rupture -avoid use w simvastatin > 20mg and pravastatin >40mg (myopathy)
87
Bempedoic trials
-reduce risk of MI
88
Red yeast rice
-lovastatin ingredient -shown to lower TC LDL TG -maybe inc HDL -same effects/interaction as statins -no regulation or guidelines for use
89
Lomitapide (Juxtapid)
-HoFH -only available through REMS -boxed warning for hepatotoxicity
90
Evinacumab (Evkeeza)
-mab for HoFH -IV infusion q4weeks
91
Guideline risk groups
-clinical ASCVD (cardiovasc event) -diabetes 45-75y/o -LDL>190 -over 75y/o -ASCVD risk >20%
92
Primary prevention groups
-pt w no ASCVD event -hypercholesterolemia -DM -over 75
93
primary prevention if LDL-C >190mg
-no risk assessment -high intensity statin (class I) -moderate if over 75
94
primary prevention in DM age 40-75
-moderate intensity statin -risk assessment to consider high-intensity
95
age >75 primary prevention
-clinical assessment -discuss risks -moderate dont really go high
96
primary prevention in ASCVD >20% under 75 y/o
-always high intensity
97
guideline slide
98
risk enhancing factors for primary prevention
-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
Secondary prevention eligibility
-past ASCVD event -MI -angina (stable or unstable) -revascularization -stroke (TIA) -Peripheral Artery Disease (incl aortic aneurysm)
100
Secondary prevention
-always high intensity statin -mod if over 75 -add zetia if too high -then go PSCK9 inhibitor
101
Patients benefiting from statin
-clinical ASCVD at any age -LDLC>190 -40-75 w DM or ASCVD risk -fam hx -risk discussion everyone else
102
Statin monitoring
-initiate statin -follow up 4-12 weeks until dose stable -follow up every 3-12 months
103
Coronary Artery Calcium test (CAC)
-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
patient groups considered for non-statin therapy
-under 75 on statin for seconday prevention -over 21 on statin for primary prevention -40-75 w DM for primary prevention
105
when to treat non-statin for secondary prevention under 75
-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
when to treat non-statin over 21 for primary prevention
-baseline LDL>190 no underlying causes -add ezetimibe if reduction <50% or LDL > 100
107
when to treat non-statin age 40-75 w DM for primary prevention
-risk assessment -ezetimibe if ASCVD risk >20% on max statin
108
non-statin recommendations after max statin
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
Treatment goals
-treat to target -primary: LDL < 100 -secondary: LDL<70 -or max tolerated for ease
110
should tx be expanded?
-meds dont reverse damage -may be beneficial to use in younger adults -still being looked at for long-term efficacy
111
Hypertriglyceridemia categories
-persistent -moderate (150-499) -severe (>500) -pt w DM have hyperTGs w high A1c (turns extra sugar into TGs)
112
persistent hyper TG
-fasting TG >150 after 4-12 weeks lifestyle intervention, stable dose of max statin, and secondary cause evaluation
113
moderate hyper TG
-excess TGs carried in VLDL -150-499
114
Severe hyperTG
>500 -excess TGs in VLDLs -elevated chylomicrons inc pancreatitis risk -high pancreatitis risk
115
HyperTG treatment
-give statin
116
Secondary TG factors
-obesity -metabolic syndrom -alc use -DM -HYPOthyroidism -liver/kidney disease -meds (slide102)
117
lifestyle mods to tx hyperTGs
-5-10% weight loss = 20% dec in TG -low fat diet -restrict alc, sugar, refined carbs -physical activity
118
Pharma tx of hyperTGs
-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
patient cases

Therapeutics II (55 decks)

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