CHAPTER 22: Drugs for Lipid Disorders

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TYPES OF LIPIDS
Triglycerides: 90% lipids in body
o Major storage form of fat
o Only lipid that serves impt E source
Phospholipids: build plasma membranes
o Lecithins: egg yolk, soy beans
Steroids: sterol nucleus/ring structure
o Cholesterol: hi level = atherosclerosis
Fxn: building block for biochem Vitamin D, bile acids, cortisol,
estrogen, testosterone
Body makes 75%; diet provides 25%
AHA: limit dietary chol to 300mg/day

LIPOPROTEINS: cholesterol + triglyceride + phospholipids + apoprotein

Packaged for blood transport b/c lipids are not soluble in plasma
HDL: highest amnt apoprotein (50%) [GOOD]
o Prod in liver, small intestine
o Fxn: reverse cholesterol transport - transport chol from body tissues liver
Chol broken down, unite w bile and excreted via feces
EXCRETION VIA BILE only route body uses to remove chol!!
LDL: highest amnt cholesterol [BAD]
o Fxn: transport chol from liver tissues, organs for synthesis of plasma
membranes, other steroids
o Atherosclerosis excess storage in lining of blood vessels, contributes to plaque
deposits, CAD
VLDL: primary carrier triglycerides in blood
o Reduced to LDL later

**Ratio: LDL:HDL = 5:1 (males); 4.5:1 (females)

LIPID DISORDERS: many people unaware, asymptomatic of condition

Dyslipidemia: abnormal (excess, deficient) level of lipoproteins
Hyperlipidemia: hi [blood lipids]; major risk factor for CV dx
Hypercholesterolemia: elevated [blood cholesterol] (specific type of hyperlipidemia)

LIFESTYLE CHANGES: goal should be maintain normal lipid values w/o pharmacotx
Diet:
o Fat <30% total caloric intake
o Chol reduced, <300mg/day
Liver reacts to lo-chol by making more chol, inhibt excretion when saturated fats
present
o SO pt must reduce BOTH saturdated and chol to reduce [chol blood]
Eating plant sterols leads to chol excretion
o Less chol delivered to liver, LDL uptake increases, decrease LDL serum level
o Ex) nuts, wheat, corn, rye, oats, rice, olive oil
CHAPTER 22: Drugs for Lipid Disorders
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HMG-CoA REDUCTASE INHIBITORS / STATINS
First line antihyperlipidemics
Effectiveness
o Reduce LDL levels 20-40%; raise HDL
o Reduce CV-related events 25-30%
Mechanism:
o Chol made in liver
o HMG-CoA reductase is primary regulatory site for chol biosyn
Normal cond: enzyme controlled via neg feedback
i.e. hi LDL shuts down HMG-CoA reductase & stops prod of chol
o Statins: inhibit HMG-CoA reductase less chol biosyn
Less chol prod, more LDL receptors made on surface of liver cells
So increase removal LDL from blood
o NOT permanent pt must remain on drugs until hyperlipidemia controlled by
diet, lifestyle changes
AEs: oral, mostly well-tolerated
o Minor: headache, fatigue, muscle/joint pain, heartburn
o Rare SAE: myopathy (musc weakness), rhabdomyolysis (breakdown of musc
fibers into systemic circulation acute renal failure)
Admin:
o Statins w/ short half lives should be given @ night because chol biosyn higher @
night
o Combine with bile acid sequestrants, niacin to boost effectiveness
o Admin with food to decrease GI discomfort
o Most preg category X!!!
Prototype: Atorvastatin (Lipitor)
Note: takes 2 wk for therapeutic effects

BILE ACID SEQUESTRANTS / Resins

No longer first line, but can be combined w statins if insufficient response
Effectiveness:
o Reduce LDL 20%
Mech:
o Bind bile acids (contain hi conc cholesterol)
o Then excreted because cant be reabsorbed d/t large size
o More LDL receptors made and more chol removed fro blood
AEs: more frequent than statins
o BUT not absorbed into systemic circ so AEs limited to GI tract
o Bloating, constipation
o Interfere w absorption of vitamins, minerals can have nutritional deficiencies
w/ extended use
Admin: 60-180mL water, non carbonated beverages, pulpy fruits to avoid GI irritation
Prototype: Cholestetyramine
CHAPTER 22: Drugs for Lipid Disorders
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NIACIN
B-complex vitamin; need 2-3g/day to reduce chol (as vitamin = 25mg/day)
Effectiveness:
o Reduce LDL 20%
Mech:
o Decrease VLDL decrease LDL
o Red triglycerides, increase HDL
AEs: more frequent than statins
o Flushing, hot flashes expected
o GI: nausea, flatulence, diarrhea
o SAE: gout, hepatotox
Contraindications: NO diabetes mellitus
Often combined w statins
Note: take 1+ mo achieve effects

FIBRIC ACID AGENT

First line for extremely hi tryglyeride levels
Effectiveness:
o Gemfibrozil 50% red VLDL; increase HDL
Mech:
o Activate lipoprotein lipase incr breakdown and elimination of triglycerides
from plasma
Admin: with meals FATTY FOODS decreases efficacy!
AEs:
o GI: diarrhea, nausea, cramping, GERD
o Gallstones, hepatotix
o Taking w statins incr risk myopathy, rhabdomyolysis
Prototype: gemfibrozil

CHOL ABSORPTION INHIBITORS

Ezetimbe
Mech: blocks absorption of chol in jejunum (sm intestine)
o BUT body responds by syn more chol
o SO must be taken w statin to be effective red LDL by addnl 15-20%
Do NOT take w/: bile acid sequestrants b/c it inhibits absorption of ezetimibe
AEs:
o Nasopharyngitis, myalgia, URI, arthralgia, diarrhea
Preg C

Also fish oil

 CHAPTER 22: Drugs for Lipid Disorders
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Class/Drug Mech AE Black box Contraindications Preg

HMG-CoA reductase Inhibit HMG-CoA enzyme Headaches, GI complaints, Serious Preg category X!! X
inhibitor less chol synthesis, incr musc/joint pain, fatigue liver dx
LDL receptors NO grapefruit juice, red yeast rice.
Atorvastatin Rhabdomyolysis, myopathy,
Take w food! hepatic damage Take w/ CoQ10 to prevent deficiency

Can combine w niacin, bile acid

sequestrants
Bile acid seqeuestrants Bind bile acids not GI only: constipation, bloating, N/A Preg category C C
reabsorbed, excreted d/t nausea
Cholestyramine lg size Taking w food can cause vit
Vitamin deficiencies deficiencies
Take w water, noncarb
bev, soup, pulpy fruits! Total biliary obstruction
Niacin B-vitamin; hi doses Flushing, hot flashes Diabetes mellitus
reduces VLDL = reduce LDL GI: nausea, flatulence, diarrhea Used in combo w statins
Hepatotox
Fibric acid agent Activate lipoprotein lipase Gallstones, hepatotox B Renal, hepatic dx, gallbladder dx
breakdown, remove GI: diarrhea, nausea, cramp
Gemfibrozil triglyerides Use w statins INCR risk myopathy,
rhabdomyolysis
Eat w food BUT fatty
food decreases efficacy
Chol absorption Inhibit chol absorption in URI, nasopharyngitis, myalgia, C Dont take w bile acid sequestrants
inhibitor sm intestine diarrhea

Ezetimibe BUT must be taken w Rhabdomyolysis

statin to be effective

Abnormal values for:

LDL, HDL, total chol, triglycerides