E3: FishOils/BileAcids/LesserUsed

Question 1

Lovaza:
Vascepa:
Omea-3 Fatty Acids:

Which one is OTC, Omega-3 Acid ethyl esters, icosapent ethyl

Advantages/Disadvantages

Answer 1

Lovaza: Omega-3 ethyl esters
+: ↓TG, ultra refined product
-: can ↑LDL

Vascepa: Icosapent ethyl
+: fishy aftertaste
-: none

Omea-3 Fatty Acids: OTC
+: lack purification, quality concern, fishy aftertaste
-: EPA/DHA content questionable

Question 2

What are the active components in omega-3 FA

Answer 2

EPA and DHA

Question 3

Omega-3 FA
MOA (2)
DI
ADR

Answer 3

MOA:
1. Inhibit diacylglycerol acyltransferase (DGAT)
↓ TG
2. ↑ lipoprotein lipase activity
can ↑ LDL when taken alone

DI: antithrombotic agents (warfarin-Coumadin®, clopidogrel-Plavix®, ↑ bleeding risks)

ADR:
1. A fib
2. Bleeding
3. GI (diarrhea, nausea, eructation
4: Fish/seafood allergy

Question 4

Bile acid resins/sequestrants (2)
General Info (2)
MOA of bile acids
How to they exhibit their LDL lowering effects
ADR
DI
CI

Answer 4

1. colesevelam-Welchol
2. cholestyramine: Questran

Info
1. Patient instructions
A. powder mix with pulpy fruit or applesauce in advance, diet soft drinks
B. taken before or with meals
Tablets: drink with plenty of fluids
2. colesevelam is FDA approved for improving glycemic control in patients with Type 2 DM, (↓ A1c)

MOA:
1. Cholesterol found in bile acids
2. Bile acid Resins
large non-absorbable anion-exchange resins that binds bile acids
Form insoluble complex in gut
NOTE: normally bile acids are recycled back into liver
3. Resin/bile acid complex gets excreted
—Physically too large to be absorbed
back

LDL lowering specifically:
1. Bile acid resins bind bile acids in the GI tract and promote their excretion
2. This enhances diversion of hepatic cholesterol to new bile acid synthesis
3. results in ↑ LDL receptor #’s on hepatic cell membranes
4. causes more plasma LDL binding to hepatic LDL receptors

ADR: GI >10%; (cholestyramine, colesevelam): constipation, bloating
GI (1-10%): nausea, heartburn, diarrhea, indigestion

DI:
-cholestyramine only: binds anionic&raquo_space; cationic, neutral drugs and ↓ intestinal absorption: furosemide, digoxin, thiazides, statins, NSAID’s, vitamins
patient instructions: take other drugs 1 - 4 hours before or 4-6 hours after cholestyramine
-↓ absorption of fat soluble vitamins (A,D,E,K)

CI: Patients with TG > 500 causes further elevations in TG

Question 5

Compare the two bile acid resins

Answer 5

Cholestyramine-Questran: Limited ionic and hydrophobic binding to resin

colesevelam-Welchol®
Both ↑ Ionic and ↑ hydrophobic binding to bile acids
↑ primary amines (+)
↑ efficacy
Leads to ↓ reabsorption of bile acid from GI tract
Eventual ↓ reabsorption of cholesterol back to the liver

Question 6

Bempedoic Acid
Indication
MOA***

Answer 6

Indication:
1. heterozygous familial hypercholesterolemia (HeFH)
2. establishedatherosclerotic cardiovascular disease(ASCVD)
–Results in ↓ synthesis of VLDL and LDL
–Efficacious in addition to maximally tolerated statins:  LDL 17-19%

MOA***
1. Activated inside liver by ACSLV1
2. Inhibits ACL (cystolic enzyme 2 steps upstream of HMG-CoA reductase which inhibits production of Acetyl-CoA –> Inhibits cholesterol synthesis)