Dyslipidemias Flashcards
2 Sources of Cholesterol
- from food
- synthesized by the liver
How are lipids transported?
- lipoproteins act as shuttles that transport the lipids to be:
- stored
- used for energy
- steroid hormone production
- bile acid formation
Types of Lipoproteins
- Chylomicrons:
- VERY large
- dietary lipid
- HDL:
- contain lower amounts of cholesterol → can extract cholesterol from the periphery and transport back to the liver
- cholesterol esters; ApoA1
- LDL: “Bad cholesterol”
- mostly cholesterol esters
- ApoB-100
- IDL: intermediate density lipoproteins
- cholesterol esters + triglycerides
- VLDL: From the liver
- endogenous triglycerides >>> Cholesterol
ApoB-100
ligand for the LDL receptor
required for VLDL assembly → without this = VLDL cannot be assembled and cannot exit liver
ApoB-48
required for chylomicron assembly
ApoE
ligand for chylomicron and VLDL remnant receptor
MOA of statins
inhibit HMG-CoA reductase which is needed for cholesterol production → no HMG-CoA reductase = reduce cholesterol production
- targets the endogenous pathway and the VLDL levels
Polygenic familial hypercholesterolemia
common primary dyslipidemia
d/t metabolic and environmental factors
LDL-C = 160-250mg/dL
Efficacy of LDL reduction of Statin Drugs in order:
- Rosie Ate Some Pizza Left For Paul
- Rosuvastatin
- Atorvastatin
- Simvastatin
- Pitavastatin
- Lovastatin
- Fluvastatin
- Pravastatin
Equivalent Dose of Statins
Peeta Rescued A Scared, Lonely, Proper Floozy
Dosed Qday
- Pita 2mg
- Rosu 5mg
- Ator 10mg
- Simva 20 mg
- Lova 40mg
- Prava 40 mg
- Fluva 80 mg
Which statins are not metabolized by CYP450
- pitavastatin
- contraindicated with cyclosporine (causes rhabdomyolysis)
- Rosuvastatin
Side Effects and Notes of Statins
- SEs:
- Elevated LFTS (d/c if 3x wnl)
- myopathy
- Notes:
- most are 3A4 inhibitors → metabolized by cyp450 (except pitavastatin, pravastatin, & rosuvastatin)
- avoid use with gemfibrozil (worsen liver toxicity & myopathy risk)
Bile Acid Sequestrants
COLE drops the BASe
-
cholestyramine
- More GI side effects
-
colesevelam
- less GI side effects
- colestipol
-
MOA:
- loss of bile → reduced cholesterol storage → upregulation of LDL receptor in liver
-
Notes:
- ***increase triglycerides***
- LDL cholesterol: -15% to -30%
- Constipation
- impairs absorption of fat soluble vitamins (A,D,E,K)
- prevents absorption of digoxin, warfarin, thiazides, thyroxine
Ezetimibe
- MOA: Niemann-Pick C1 like 1 transporter blocker → inhibit cholesterol absorption
- well tolerated
- SEs:
- oily diarrhea
- bloating and distention
Indications for Nicotinic Acid
High TG
High LDL
Low HDL
MOA of Nicotinic Acid (Niacin, Vitamin B3)
inhibit fatty acid release from adipose tissue & inhibits fatty acid and triglyceride synthesis from the liver → increases intracellular degradation of Apo-B → reduce VLDL release; reduce uptake of HDL → more HDL present in blood → increase uptake of cholesterol
SEs & Notes of Nicotinic Acid
used to decrease LDL, TGs, and increase HDL
- SEs: flushing, pruritus
- can pre-medicate with ASA or NSAIDs 30 min prior to prevent these SEs
- hepatotoxicity
- increase uric acid levels
- increase blood sugar levels (but still okay to use with DM pts)
- Nicotinamide (no flush) aka “no flush” formulation → has no role in treating hyperlipidemia
Fibrates
- decrease TGs, increase HDLs, decrease or increase LDLs
- MOA: unclear, inhibits TG synthesis and stimulates breakdown of TG-rich lipoproteins; activation of peroxisome proliferator-activated receptor alpha (PPAR-alpha)
- reduce ApoB, C-3, E
- increase ApoA1, 2
-
Fenofibrate
- pro-drug that gets converted to fenofibric acid
- half life = 1 day
- 5 half lives to eliminate from body = 5 days
- Fenofibric Acid
-
Gemfibrozil
- DDI: with statins = rhabdomyolysis
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- DDI: with statins = rhabdomyolysis
Fibrates SEs, Contra-Indications, Max Effect
- decrease TGs, increase HDLs, but can increase or decrease LDLs
- SEs:
- dyspepsia
-
muscle pain (myopathy, rhabdomyolysis)
- occurs in renal dysfunction
-
combo with statins (esp gemfibrozil → AVOID)
- prefer: fenofibrate
-
Contra:
- gallbladder disease; liver dysfxn
- severe kidney dysfxn
-
Max Effect:
- fenofibrate: 2 weeks
- gemfibrozil: 3-4 weeks
- takes a while to start working
Omega-3 fatty acids
- Long chain fatty acid in fish oil
- lowers TGs up to 45%
- modulated PPAR-alpha receptors → reduced ApoB-100 production → less VLDL
- Notes:
- reduces platelet aggregation
- antiarrhythmic (reduction of MI/cardiac death)
- SEs:
- diarrhea
- bleeding → DDI anticoagulant and antiplatelet
- increased risk of hemorrhagic stroke
Icosapent (Vascepa)
indication: high TG > 500mg/dL
- MOA: icosapent ethyl → eicosapentaenoic acid (EPA: active metabolite) → reduces hepatic VLDL-TG synthesis, increases TG clearance
- SEs:
- arthralgias
- Metabolism: liver only (no renal excretion)
- Precaution: allergy to fish/shellfish, prolonged bleeding time
PCSK9 inhibitors
indication: use with statin for familial hypercholesterolemia or clinical ASCVD
-
Drug names:
- Alirocumab
- Evolocumab
- decreases LDL-C 40-60%
- biologix used to prevent endocytosis of LDL receptor in liver
-
SEs:
- injx site rxn
- nasopharyngitis
- influenza
- allergic rxn
- EXPENSIVE
ASCVD Treatment Groups
- pts with clinical ASCVD (secondary prevention)
- pts >21 yrs with LDLD >190mg/dL
- pts with pooled cohort 10 year risk score >7.5%
- pts 40-75 with diabetes
ASCVD risk score and tx
for age 40-75 and LDL-C ≥70- <190mg/dL:
- <5%: low risk
- emphasize lifestyle modification
- 5%-7.5%: borderline risk
- if risk enhancers present → discuss moderate intensity statin
- ≥7.5%-<20%: intermediate risk
- risk estimate + risk enhancers → favors moderate intensity statin to reduce LDL-C by 30-49%
- ≥ 20%: high risk
- high-intensity statin → reduce LDL-C by 50%
“Risk Enhancers” in the ASCVD risk score
- family hx of premature ASCVD
- persistently elevated LDL-C ≥ 160mg/dL or elevated TGs ≥ 175mg/dL
- CKD
- metabolic syndrome
- pre-eclampsia, premature menopause
- inflammatory diseases (HIV, RA, psoriasis)
- Ethnicity (South Asian Ancestry)
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