Exam 1: Lecture 12, Hyperlipidemia Flashcards
what is leading cause of death for most racial/ethic groups in US?
Heart disease
Key heart disease risk factors
High BP, High LDL cholesterol, and smoking
Lipoproteins
complexes of lipids and proteins that transport lipids through the plasma
Hyperlipoproteinemias/hyperlipidemias
metabolic disorders that involve elevations in any lipoprotein species
Apolipoproteins
The protein constituents of lipoprotein particles that play a key role in transporting cholesterol, triglycerides, phospholipids, and fat-soluble vitamins between the intestine, liver and peripheral tissues
“Good” cholesterol
HDL
Statin prototype:
Lovastatin
Statin MOA:
Competitive inhibitors of HMG-CoA reductase, which catalyzes an early, rate-limitng step in cholesterol biosynthesis
Statins Applications:
Hyperlipidemia
Statins Notables:
First pass effect
Drug-Drug interactions related to CYP3A4
Liver toxicity, muscle breakdown (myopathy)
Not for pregnant people, baby needs cholesterol
No grapefruit * 6+/day *
Drugs in Statin class?
Lovastatin Pravastatin Simvastatin Rosuvastatin Atorvastatin
High intensity statins?
Lower LDL-C by 50% or more
Atorvastatin 40-80mg
Rosuvastatin 20-40 mg
Moderate-intensity statins?
Lower LDL-C by 30% - <50%
A bunch
Low-intensity statins?
Lower LDL-C, on average by < 30%
A bunch, lower dose than moderate-intensity
MOA Statins detailed
- Inhibit HMG-CoA reductase, leading to decreased conc of cholesterol within cell
- Low intracellular cholesterol stimulates the synthesis of LDL receptors
- Increase number of LDL receptors promotes uptake of LDL from blood
- Low intracellular cholesterol decreases secretion of VLDL.
Clinical Application statins
Intensive statin treatment leads to no change in lumen size but decrease in lipid core.
Will also cause increase in fibrous and calcified tissues
Bile acid-binding resins: Prototype
Cholestyramine
Bile acid-binding resins: MOA
bind bile acids in GI tract and promote excretion
Bile acid-binding resins: Applications
Primary hypercholesterolemia
Bile acid-binding resins: Notables
in patients who also have hypertriglyceridemia, VLDL levels may be increased during treatment
Bloating, and effect drug absorption (don’t use if on many other drugs)
Drugs in Bile acid-binding resins class?
Cholestyramine
Colestipol
Bile acid-binding resins MOA detailed:
Bile acid binding resin will bind to the cholesterol along with bile and cause it to be excreted.
can have GI complications, not 1st line
Nicotinic acid: prototype
Niacin (Vitamin B3)
Nicotinic acid: MOA
Inhibits VLDL secretion, decreasing production of LDL
Nicotinic acid: Applications
Combo with resin or reductase inhibitor will normalize LDL in most patients with heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia
Nicotinic acid: Notables
Hepatotoxicity, platelet deficiency, birth defects w/ high dose, tachycardia, flushing, diarrhea, itchiness, dry skin
Fibrates: Prototype
Gemfibrozil
Fibrates: MOA
Function primarily as ligands for nuclear transcription receptor PPAR-a
up regulate LPL, apo A-I, and apo A-II
down regulate apo C-III (inhibitor of lipolysis)
Fibrates: Applications
Hypertriglyceridemias in which VLDL predominate
Fibrates: Notables
Stomach aches, gas
** Rare **: rashes, GI symptoms, myopathy, arrhythmias
Ezetimibe prototype
Its own prototype
Ezetimibe MOA
Inhibits NPC1L1 mediated cholesterol reabsorption
Ezetimibe Applications:
Hypercholesterolemia, synergistic with reductase inhibitors
Ezetimibe Notables:
Reversible impaired hepatic function, myositis (inflamed muscle)
PCSK9 inhibitors
Alirocumab
Evolocumab
PCSK9 inhibitors MOA
Bind to PCSK9, inhibiting it from binding to LDL receptor.
This increases the number of LDL receptors available to clear LDL, thereby lowering LDL-c levels.
Normally PCSK9 promotes degradation of receptors
Dietary Management of Hyperlipoproteinemia
total calories from fat should be <25%
Saturated fat <7%
Cholesterol <200mg/day
What increase VLDL?
Sucrose and fructose
Principal factors increasing LDL?
Cholesterol, saturated and trans fats
What do Omega 3 fatty acids do?
Activate PPARa = reduce tyiglycerides
Lomitapide MOA:
prevents apoB and Triglycerides from coming together and prevents VLDL loading.
Inhibits MTTP
Mipomersen MOA:
Mipomersen is an antisense strand that binds to ApoB mRNA
Prevents the translation and synthesis of ApoB-100, causing decrease VLDL, leading to decrease LDL-C
Exogenous pathway
internalization of lipids
chlymicron formed, goes into capillaries
LPL releases Free Fatty Acids and returns to liver by engaging with LDLR
Endogenous
VLDL with ApoB-100 on it released by liver and goes into capillary
LPL releases FFA and IDL returns to liver or forms LDL which can bind on peripheral tissues
value of HDL?
being able to scavenge a lot and in peripheral tissues
