Dyslipidemia

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Enterohepatic recycling

The bile acids travel from the liver through the bile ducts (with free cholesterol and
waste products) and into the small intestine. Bile acids in the small intestine are
needed to absorb fat. The acidic environment in the intestine converts the bile acids
into bile salts, in order to be able for recycled from the intestine and returned to the
liver.

Cholesterol carring by lipoproteins

There are two types of lipoproteins carrier which serve as a carrier for triglycerides
(TG) :
HDL and Non-HDL.

High-density lipoproteins (HDL): it's calld Good Cholesterol : Responsible for

transporting cholesterol from the blood to the liver.

Non-HDL (Bad Cholesterol) : Responsible for transporting cholesterol from the

liver to the blood. Inclode Non-HDL are : low-density lipoproteins LDL and
very-low density lipoproteins VLDL

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 Classification of dyslipidemia

Primary is hereditary.

Secondary (or Acquired):

Severe elevations due to diet, drug and other conditions

(including LDL > 190 mg/dL and TG > 500 mg/dL) must be evaluated and treated
appropriately.

Classification of cholesterol and TG levels (mg/dl)

Non-HDL

< 130 Desirable

130 - 159 Above desirable

160 - 189 Borderline high

190 - 219 High

≥ 220 Very high

LDL

< 100 Desirable

100 - 129 Above desirable

130 - 159 Borderline high

160 - 189 High

≥ 190 Very high

HDL

< 40 men Low

< 50 Women Low

Triglycerides

< 150 Desirable

150 - 199 Borderline high

200 - 499 High

≥ 500 Very high

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 Non-drug treatment
The following recommendations should apply :

Maintain a healthy weight

Diet should be rich in vegetables, fruits, whole grains, and high-fiber foods.

Consume fish, especially fish with a high-fat content (rich in omega-3 fatty
acids).

Limit intake of saturated fat, trans fat (partially hydrogenated).

Limit intake of added sugars and salt.

Engage in aerobic physical activity 3 - 4 times per week lasting 40

minutes/session.

Avoid tobacco products and limit alcohol consumption.

Natural products

Fibrous foods (found in psyllium, barley, oat bran)

Artichoke extract.

Calculating ASCVD risk

The global risk assessment tool is used to provide an estimate of an individual's risk
of having a first cardiovascular event (e.g., MI, stroke, or death) during the next 10
years. This is called the 10-year ASCVD risk.

A 10- year ASCVD risk of > 7.5% is an indication to start statin therapy for primary
prevention in individuals age 40 - 75 years.
ASCVD risk repeated every 4 - 6 years if the risk is (< 7.5%).
Statin Treatment Intensity Based on Patient Risk

Treatment principles
American College of Cardiology and the American Heart Association guidelines
Many of the cholesterol-lowering drugs can cause liver damage (niacin, fibrates,
ezetimibe and potentially statins). Liver enzymes should be monitored and the drug
stopped if the AST (10 - 40 units/L) or ALT (10 - 40 units/L) is > 3 times the upper
limit of normal.

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 Statins are the drugs of choice in treating elevated non-HDL and LDL. If a patient is
completely statin intolerant or needs an additional LDL lowering drug. Guidelines
focus on the use of ezetimibe and PCSK9 inhibitors over other non-statin drugs.

mayoclinicproceedings, High-Intensity Statins Benefit High-Risk Patients: Why and How to Do

Better, Copyright Notice.

1- Statins

💡 Pitavastatin, Rosuvastatin, Atorvastatin, Simvastatin, Lovastatin,

Pravastatin and Fluvastatin.

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 💡 intrnisity of Statins:

https://ehhapp.org/StatinIntensity , Copyright Notice.

💡 MOA: Inhibit the enzyme 3- hydroxy-3- methylglutaryl coenzyme A (HMG-

CoA) reductase, which prevents the conversion of HMG-CoA to
mevalonate. This is the rate-limiting step in cholesterol synthesis.

💡 CI: Active liver disease, pregnancy and breastfeeding.

Use with colchicine or cyclosporine and strong CYP3A4 inhibitors.

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 💡 SE: Myalgias, arthralgias, myopathy, diarrhea, cognitive impairment

💡 Monitoring: Liver function tests (LFTs) and lipid panel and (PT/INR for
patients on warfarin)

💡 Note: (simvastatin and lovastatin) are taken with evening meal.

Adverse effects of statin drugs is muscle damage and some patients may
attempt to self-treat with natural products (e.g., Coenzyme Q10 and
vitamin D supplements), but evidence of benefit is limited.

2- Ezetimibe

💡 MOA: Inhibits absorption of cholesterol in the small intestine

💡 CI: Active liver disease, pregnancy, breastfeeding, may increase risk of

myopathy, rhabdomyolysis when combined with a statin.

💡 SE: Myalgias, diarrhea, URTIs, arthralgias, pain in extremities, sinusitis

💡 Monitoring: Liver function tests (LFTs)

💡 Note: give ezetimibe two hours before or four hours after bile acid
sequestrants.

3- Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9 I's)

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 💡 Alirocumab and evolocumab

💡 MOA: PCSK9 inhibitors are human monoclonal antibodies that bind to

(PCSK9).
Because PCSK9 binds to the LDL receptors leads to blocking the
degradation process of LDL.

💡 CI: Allergic reactions

💡 SE:Injection site reactions, nasopharyngitis, influenza.URTIs, UTI.back

pain (evolocumab), T LFTs (alirocumab)

💡 Monitoring: LDL-C

💡 Note: Both indicated for heterozygous familial hypercholesterolemia

(HeFH) or ASCVD as an adjunct to diet and maximally tolerated statin
therapy.
Evolocumab: indicated to reduce the risk of cardiovascular disease.
indicated for primary hyperlipidemia and as an adjunct in homozygous
familial hypercholesterolemia (HoFH).

4- Bile acid sequestrants/ bile acid binding resins

💡 Cholestyramine, Colesevelam, Colestipol

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 💡 MOA: Bind bile acids in the intestine, forming a complex that is excreted
in the feces.

💡 CI: Colesevelam: bowel obstruction.TG > 500 mg/dL, history of

hypertriglyceridemia-induced pancreatitis.

💡 SE: Constipation, abdominal pain, cramping, bloating, gas, increase TG.

decreas absorption of fat- soluble vitamins.

💡 Note: Colesevelam can be considered as an option in a pregnant patient

5- Fibrates

💡 Fenofibrate or Fenofibric Acid and Gemfibrozil.

💡 MOA: Peroxisome proliferates receptor alpha (PPARa) activators, which

upregulate the expression of apolipoprotein C2 (apoC-Il) and
apolipoprotein A1 (apoA-l). which leads to increased catabolism of VLDL
particles.

💡 CI: Severe liver disease, Severe renal disease, Gallbladder disease

(fenofibrate derivatives only): breastfeeding
(gemfibrozil) should not be given with ezetimibe or statins.
increas risk of Myopathy when coadministered with a statin.

💡 SE: Dyspepsia, increas LFTs, abdominal pain, increas CPK.URTIs.

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 💡 Monitoring: LFTs, renal function

💡 Note: fibrate therapy can lead to an increase in LDL.

6- Niacin / vitamin B3

💡 MOA: decreases the rate of hepatic synthesis of VLDL (decreases TG)

and LDL; can also increase the rate of chylomicron TG removal from
plasma Can not affecting HDL.

💡 CI: Active liver disease, active PUD, arterial bleeding

💡 SE: Flushing, pruritus (itIching).N/V/D, hyperglycemia, hyperuricemia (or

gout), cough, orthostatic hypotension. hypophosphatemia, decrease
platelets

💡 Monitoring: LFTs, lipid profile, blood glucose (if have diabetes), uric acid (if
have gout), INR (if on warfarin)

💡 Note: Doses for cholesterol reduction are much higher than doses found
in multivitamin products. Take niacin 4 - 6 hours after bile acid
sequestrants.

7- Fish oils / omega-3 fatty acids.

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 💡 MOA: not completely understood; may reduce hepatic synthesis of TG.
These are indicated as an adjunct to diet when TG > 500 mg/dL

💡 CI: hypersensitivity to fish and/or shellfish

💡 SE: Eructation (burping), dyspepsia, taste perversions, arthralgias

,flatulence.

💡 Monitor: INR (if on warfarin).

💡 Note: Stop prior to elective surgeries due to increased risk of bleeding

8-Specialty Drugs

💡 Lomitapide and mipomersen

💡 MOA: Decrease apoB, which is the main component of LDL and VLDL
(the precursor to LDL).
Lomitapide binds to and inhibits microsomal triglyceride transfer protein
(MTP), which prevents the assembly of apoB containing lipoproteins.
Mipomersen is an oligonucleotide inhibitor of apoB synthesis.

💡 CI:Activeliverdisease, Lomitapide: pregnancy

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 💡 SE: N/V/D, dyspepsia, abdominal pain, constipation, flatulence, increase
LFTs, chest pain, back pain, fatigue, weight loss, influenza,
nasopharyngitis.
Mipomersen: Injection site reactions, flu-like symptoms, antibody
formation

💡 Monitoring: LFTs, alkaline phosphatase, lipids.

💡 Note: Both medications are approved for use in patients with homozygous
familial hypercholesterolemia (HoFH).

Questions PDF Page

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