Patho of Dyslipidemia Flashcards
Patho of Atherosclerosis
1) endothelial injury
2) ___ response
3) ___ infiltration
4) platelet adhesion
5) smooth muscle cell ___
6) extracellular ___ accumulation
- inflammatory
- macrophage
- proliferation
- matrix
T or F: dyslipidemia is largely asymptomatic
T
but depending on severity and duration of disease, the following can occur:
- chest pain
- palpitations
- sweating
- anxiety
- SOB
- Loss of consciousness
- difficulty with speech or movement
- abdominal pain
Signs
- we worry about ___ when TGs are over ___ - ___
- eruptive ___
- peripheral ___
- increase BP
- waist size greater than ___ in men and ___ in women
- BMI greater than ___
- pancreatitis, 400-500
- xanthomas
- polyneuropathy
- BP
- 40, 35
- 30
Lab Parameters
- LDL- ___ - amount of cholesterol in LDL
- LDL- ___ - number of LDL particles
- Non-HDL-C: amount of cholesterol in atherogenic particles. non HDL-C = TC - HDL
- Apo - ___ - number of atherogenic particles
C, P, B
Lab Parameters
ApoB, LDL-P, and non-HDL-C
- all valid in ___ sample and with elevated ___ levels
- all more predictive of future CVD risk than ___ alone
not routinely ordered
- non-fasting
- LDL-C
What is included in a FLP (4)
- TC
- TG
- HDL-C
- LDL-C
Friedewald Equaton
used to estimate ___ from FLP
- not valid when TG > ___ mg/dL
LDL = ___
LDL
- 400
- TC - HDL - TG/5
non-fastin sample: ___ and ___
TC:HDL goal ratio: less than or equal to ___ : ___
- optimal (___ - ___ :1)
TC, HDL
5:1
3-3.5
LSM
- ___ diet, USDA food pattern, AHA diet
- reduce percent of calories for ___ and ___ fats (5-6% of calories from sat fats)
- lower ___ intake ( < 1,000 mg/day)
- moderate to vigorous aerobic physical activity
- DASH
- trans, saturated
- sodium
____ kcal/1 gram of saturated fat
9
Therapeutic Lifestyle Changes
- soluble fiber to decrease ___
- oat bran
- pectins or gums
- ___ products (binds cholesterol in gut and reduces hepatic production and clearance, 10-15 grams daily may decrease ___ and ___ by 20%)
LDL
psyllium
LDL, TC
Therapeutic Lifestyle Changes
- Plant stanols and sterols (2-3 grams daily decreases ___ 6-15%) Example: ___
- weight reduction
- increased physical activity
- smoking cessation
LDL
Benecol
Omega-3 Fatty Acids
Fish oil/Omega-3 fatty acids
- EPA/DHA
- reduces ___, may increase ___ by 4-49%
___ : 2-4 gms daily or divided BID
___ : 2 gms po BID with food
- IPE: only TG
IPE - icosapent ethyl
TG, LDL
Lovaza
Vascepa
HMG-CoA Reductase inhibitors
- Altoprev, Mevacor
- Pravachol
- Livalo
- Zocor
- Lescol
- Lipitor
- Crestor
- lovastatin
- pravastatin
- pitavastatin
- simvastatin
- fluvastatin
- atorvastatin
- rosuvastatin
High dose (mg) statin efficacy rank (most to least)
1) rosuvastatin (40 mg)
2) atorvastatin (80 mg)
3) simvastatin (40 mg or 80 mg)
4) pravastatin (80 mg) = lovastatin (80 mg) = pitavastatin (4 mg) = fluvastatin (80 mg)
Statin Intestity - Low
- simvastatin ___ mg
- pravastatin ___ - ___ mg
- lovastatin ___ mg
- fluvastatin ___ - ___ mg
- 10 mg
- 10-20 mg
- 20 mg
- 20-40 mg
Statin Intestity - Mod
- atorvastatin ___ - ___ mg
- rosuvastatin ___ - ___ mg
- simvastatin ___ - ___ mg
- pravastatin ___ - ___ mg
- lovastatin ___ - ___
- fluvastatin ___ mg BID
- fluvastatin XL ___ mg
- pitavastatin ___ - ___ mg
- 10-20 mg
- 5-10 mg
- 20-40 mg
- 40-80 mg
- 40-80 mg
- 40 mg
- 80 mg
- 1-4 mg
Statin Intestity - High
- atorvastatin ___ - ___ mg
- rosuvastatin ___ - ___ mg
- 40-80 mg
- 20-40 mg
which statins are hydrophylic and will not cross BBB (2)
- pravastatin
- rosuvastatin
which statins are metabolized by CYP3A4 (3)
- lovastatin
- simvastatin
- atorvastatin
Statin Clinical Trials
1) IMPROVE-IT
2) SEARCH
1) zetia + statin = good. reduced CV events and lowered LDL
2) simvastatin 80 mg shouldnt be started in new patients bc of myopathy. Can only be used if patient has been on it for awhile and are fine
Statins: Important Considerations
- obtain LFTs at baseline, repeat when clinically indicated, DC if LFTs are ___ x upper limit normal
- myopathy/rhabdomyolysis
- muscle pain and ___ urine
- avoid grapefruit juice (> 1 ___ )
- contraindicated in pregnant women
3
dark
quart
characteristric predisposing to statin side effects
- impaired renal or hepatic function
- prior statin intolerance or ___ disorders
- unexplained ALT elevations greater than ___ x upper limit normal
- other drugs that affect statin metabolism
- > ___ years of age
- hepatic, renal
- muscle
- 3
- 75
Muscle pain on statins
- ___ statin and evaluate for rhabdomyolysis
- evaluate for exacerbating conditions
- restart same for lower dose once symptoms resolve
DC
Statin Contraindications
- acute ___ disease
- unexplained, persistent elevations of serum ___
- ____ and ____
- liver
- transaminases
- pregnancy, breastfeeding
Statins and Muscle Injury
- muscle injury is ___ with statin monotherapy
- may experience myalgias without elevated ___ ___ . (> 10x upper limit of normal: ___ statin)
- risk of muscle injury is increased when taking statins extensively metabolized by ___ and drugs that interfere with ____
- uncommon
- creatine kinase, DC
- CYP3A4, CYP3A4
T or F: if patient experiences muscle pain, switch to lipophilic statin
FALSE, hydrophylic
cannot cross BBB
Statin Alternative dosing
- to improve utilization or tolerability and decrease cost: every ___ day and once ___ dosing
- intitial data for ___, ___, and ___ suggest that ___ the daily dose if necessary for every ___ day to achieve similar LDL lowering
- other, weekly
- fluvastatin, atorvastatin, rosuvastatin, double, other
Simvastatin Considerations
Contraindicated drugs (11)
- itraconazole
- ketoconazole
- posaconazole
- erythromycin
- clarithromycin
- telithromycin
- HIV protease inhibitors
- nefazodone
- gemfibrozil
- cyclosporine
- danazol
Simvastatin Considerations
do not exceed 10 mg simvastatin daily with (2)
- verapamil
- diltiazem
Simvastatin Considerations
do not exceed 20 mg simvastatin daily with (3)
- amiodarone
- amlodipine
- ranolazine
Statins and hyperglycemia
JUPITER - 27% increase in reported ___ (rosuvastatin vs placebo)
PROVE-IT TIMI 22 - ___ leading to worse glycemic control
Takeaways: benefits still outweigh risks
diabetes
atorvastatin
Statin Monitoring
FLP
- baseline
- ___ - ___ weeks following statin initiation
- every ___ - ___ months, as clinically indicated (insurance typically only allows ___ )
Consider
- baseline ___ in individuals with increased risk of adverse muscle effects
- ___ while on statin therapy in individuals with ___ symptoms
- ___ function in individuals with symptoms of ___
- 4-12
- 3-12, yearly
- CK
- CK
- hepatic, hepatotoxicity
Bile Acid Resins
- ___ (Questran, Prevalite)
- ___ (Colestid)
- Colesevelam ( ___ )
- cholestyramine
- colestipol
- WelChol
Bile Acid Resins
decrease ___ and ___
disadvantages:
- may increase ___
- take other medications ___ hr before or ___ hr after BAR
GI side Effects: constipation, bloating, nausea, flatulence
Adverse Effects:
- impaired adsorption of ___ soluble vitamins ___ , ___ , ___ , and ___
- ___ natremia
- ___ chloremia
- ___ obstruction
can also be used as a stool softener
- LDL, Cholesterol
- TG
- 1, 4
- fat, A, D, E, K
- hypernatremia
- hyperchloremia
- GI
BAR Contraindicatoins
Cholestyramine
- complete ___ obstruction
Colesevelam
- Hx of ___ obstruction
- serum TG > ___ mg/dL
- Hx of ___ induced pancreatitis
- biliary
- bowel
- 500
- hypertriglyceridemia
BAR Interactions
may decrease effect of (9)
- acetaminophen
- TzDs
- OC
- corticosteroids
- ezetimide
- fibrated
- thiazide diuretics
- warfarin
- digoxin
Niacin (Niacor, Niaspan, Slo-Niacin)
OTC
- not federally regulated
- some marked no flush, do not have free ___ and are ineffective in treating dyslipidemia
- ___ release assocaited with increased risk of hepatotoxicity
Prostaglandin mediated flushing and itching
- administer ___ 325 mg 30 min before taking
- take close to ___ times
- avoid alcohol and hot drinks (worsen flushing)
- increase ___
- hyper ___ and hyper ___
- may increase levels of ___
- nicotinic acid
- sustained
- ASA
- meal
- LFT
- hyperglycemia, hyperuricemia
- statins
Niacin Contraindications
- active ___ disease
- significant/unexplained persistent liver ___ elevations
- active ___
- arterial ___
- hepatic
- transaminase
- peptic ulcer
- hemorrhage
Niacin Clinical Trials
- Coronary Drug Project (CDP)
- ARBITER 6-HALTS
- AIM-HIGH
- HPS2-THRIVE
takeaways: is there a benefit to adding niacin? ___
NO
Chlesterol Absorption inhibitor
Ezetimibe (Zetia)
- combination product with ___ (Vytorin)
- can further decrease ___ by 12-20% when combined with statins
simvastatin
LDL
Chlesterol Absorption inhibitor
Ezetimibe
AE (3)
Contraindications
- concomitant use with a __ and active ___ disease or ___ elevations
- pregnancy and breast feeding when used concomitantly with ___
- fatigue, diarrhea, GI upset
- statin, hepatic, transaminase
- statin
Exetimibe Clinical trials
- ENHANCE
- SHARP
- IMPROVE-IT
- EWTOPIA 75
Takeaways: ezetimbibe will reduce ___ events when combined with ___
CV, statins
Fibrates
SE:
- GI disturbances
- Rash
- myalgia
- dizziness
Contraindications
- Hx of ___ disease
- ___ or dialysis
- persistnet ___ disease
- gallbladder
- ESRD
- liver
Fibrates increase levels of these 4 drugs…
- statins
- ezetimibe
- SUs
- warfarin
Fibrate Clinical Trials
- ACCORD Lipid: no increased benfit
- FIELD: reduced nonfatal MI only in T2DM
- VA-HIT: CHD events reduced by 11% with gemfibrozil for very 5 mg/d: increase in HDL
eh
PSCK9 Monoclonal Antibodies
Alirocumab ( ___ ) and ___ (Repatha)
- Indications: reduce LDL in familial ___ hypecholesterolemia or ASCVD
- MOA: inhibits binding of PSCK9 to ___ recptors and upregulates the recycling of ___ , resulting in a drastic decrease in ___
- AE: GI upset, increase ___ , injection site rxn, myalgia, flu like symptoms
Praluent, evolocumab
- heterozygous
- LDL, LDL-R, LDL
- LFTs
PCSK9 mAbs should be considered for…
- ASCVD risk reduction on max tolerated statin therapy with or without ezetimibe, and LDL-C greater than ___ or non-HDL-C greater than ___
- very high risk/ statin intolerance
- Further reduction of LDL-C if pretreatment LDL-C is greater than ___ (on max statin and ezetimibe)
- 70, 100
- 190
Odyssey Outcomes Trial
Intervention: Alirocumab lowered major adverse ___ events, lowered ___
cardiac, LDL
Inclisiran ( ___ )
- Lowers ___ and ___
- indicated for ___ hypercholesterolemia or ___
- MOA: long acting synthetic ___ that inhibits translocation of ___ protein thus inhibits its production. Prolongs activity of ___ receptors
- initial dose, 2nd dose ___ months later, then ___ months later
AE:
- inj site reactions
- arthralgia
- UTI
- diarrhea
- bronchitis
- pain in extremities
- dyspnea
Leqvio
- LDL, cholesterol
- heterozygous, ASCVD
- siRNA, PCSK9, LDL
- 3, 6
ORION Trials
- ORION 9, 10 and 11: lowers LDL really well (39.7%, 52.3% and 49.9% compared to placebo)
- ORION 5 - evaluating efficacy in ___ familial hypercholesterolemia
- ORION 4 - evaluating efficacy in ___
- homozygous
- ASCVD
Bempedoic Acid
Brand: ___ , ___
- indication: adjunt to diet and statin to reduce ___ in familial ___ hypercholesterolmia or ___
- MOA: inhibits ___
- AE: URTI, muscle spasms, hyperuricemia, back pain, abdominal pain, bronchitis, pain in extremity, anemia, and elevated liver enzymes
- Warnings and Precautions: may increase blood uric acid levels and lead to the development of ___
- risk of ___ rupture
- avoid concomitant use with ___ > 20 mg and ____ > 40 mg (myopathy)
Nexletol, Nexlizet
- LDL, heterozygous, ASCVD
- ACLY
- gout
- tendon
- simvastatin, pravastatin
Bempedoic acid Clinical trials
CLEAR TRANQUILITY
CLEAR HARMONY CLEAR SERENITY
CLEAR WISDOM
CLEAR OUTCOMES
Works well
addition medications
red yeast rice
- active ingredient: ___
- shown to lower ___ , ___ , and ___ as well as __- events, and possible increase ___
- same AE and interactions as statins
- no standardization
lovastatin
- TC, LDL-C, TG, CV, HDL
Additional Medications
lomitapide ( ___ )
- microsomal ___ transfer protein inhibitor ( ___ )
- indicated as adjunct to low fat diet and other lipid lowering treatments to reduce ___ , ___ , ___ , and ___ in patients with ___ familial hypercholesterolemia
- boxed warning for ___
- only available through ___ program
Juxtapid
- triglyceride (MTTP-I)
- LDL, TG, ApoB, non-HDL-C, homozygous
- hepatotoxicity
- REMS
Lomitapide Mechanism
1) directly binds and inhibits ___ ___ ___ ___ (MTP), therby preventing the assembly of ___ containing lipoproteins in enterocytes and hepatocytes
2) inhibits the synthesis of ___ and ___
3) leads to reduced levels of plasma LDL-C
- microsomal triglyceride transfer protein, ApoB
- chylomicrons, VLDL
evinacumab MOA
binds to and inhibits ___ (angiopoietin-like protein 3) and rescues/allows ___ and ___ to promote ___ processing and clearance from ___ formation
- ANGPTL3
- LPL, EL, VLDL, LDL
Additional Medications
evinacumab ( ___ )
- recombinant human monoclonal antibody indicated as an adjunct therapy to other lipid lowering therapies to reduce ___ in adults AND ___ patients greater than ___ yo with ___ familial hypercholesterolemia
- ___ infusion once ___
Evkeeza
LDL-C, pediatric, 12
homozygous
- IV, monthly
