Background

• Cholesterol is made in the liver and is essential in cell membranes formation, hormone, fat-soluble vitamin production. Excessive cholesterol can lead to atherosclerosis (buildup of plaque) in arteries, resulting in CHD (coronary heart disease). CHD can cause angina due to reduced blood flow to the heart muscle (narrowing of arteries)
• This is a relatively straightforward chapter to a lot of people, please pardon that I may include fewer annotations for the materials. Just don’t get caught up on the specificities of guidelines like age requirement of DM patients to be on lipid therapies, or clinical ASCVD, LDL upper and lower limits, e.g 190 vs 180, however, a 100 or 200 should stand out to you as normal or out of range.

Risk factors (RF)

• Age (men >45, women >55), smoking, HTN, HDL < 40, family history of premature CHD (<55 men, <65 female)
• Negative risk factor: HDL >60

CHD

• History of MI, unstable/stable angina, coronary artery procedure (CABG, angioplasty)
• Think major events.

 CHD equivalent

• DM, atherosclerotic disease (peripheral/carotid artery dx), abdominal aortic aneurysm, clinical CHD (Framingham calculated 10-yr risk >20%)

• Think less prominent events compared to CHD.

Category of risk

• As you move up with higher risks of CHD, the LDL goal becomes more aggressive.

Risk	LDL goal
High risk (CHD or equivalent) 10-yr risk >20%	<100
Moderately high risk 10-yr risk 10-20%	<130
Moderate risk 10-yr risk <10%	<130
Low risk 0-1 risk factor	<160

Very high risk (LDL < 70)

• For every high risk, notice the goal is even more stringent.
• CVD plus one of (DM, severe RF, metabolic syndrome (TG> 200, HDL <40)).

 

Offending drugs

• PI (protease inhibitor), anabolic & corticosteroids, BBs, thiazides, phenytoin, BCs, isotretinoin, cyclosporin/tacrolimus.

 

Healthy levels

 

LDL	<100 optimal, 100-129 near optimal
HDL	> 40
TG	<150 normal
CH	<200 desirable

 

  Statin

• MOA: Reduce HMG-CoA reductase, an enzyme in the liver that catalyzes the cholesterol synthesis
• SE: myalgias, rhabdomyolysis (increased risk w/ higher dose of pitavastatin)/ myopathy, increase LFT (stop if AST/ALT 3 times normal value) & liver damage (brown/dark urine, pale stool, eye whites become yellow).
• Trick: Liver is where fatty acids are primarily metabolized and processed, thus lipid-reducing drugs would affect the liver more. Other drugs (more lipophilic) would also be metabolized by the liver instead of the renal route (more hydrophilic). With this in mind, it can help us make sense of many difficult concepts and understand/solve many exam questions.
• Adjust dose in CrCl <30, except Lescol & Lipitor (Please review the foundation chapter on dose adjustment for the helpful pattern).
• CI: active liver disease, Pregnancy category X, nursing
• Potency conversion

Pitavastatin (Livalo) 1mg
Rosuvastatin (Crestor) 2.5mg	May increase INR, 5mg in cyclosporin, 10mg in lopinavir/ritonavir, avoid gemfibrozil
Atorvastatin 5mg (Lipitor + amlodipine = Caduet) Simvastatin 10mg (Zocor) Lovastatin 20mg (Mevacor, Altoprev ER) : take w/ meal	Increased risk of muscle damage w/ amiodarone and 3A4 inhibitors, limit to 10mg of simvas w/ cyclosporin, danazol, gemfibrozil Limit to 20mg in amiodarone, verapamil (or 40mg lovas) Limit to 40mg in diltiazem Avoid using simvas 80mg (myopathy risk 6X) Avoid grapefruit
Pravastatin20mg (Pravacol)
Fluvastatin 40mg (Lescol)	Minimal CYP metabolism

 

Ezetimibe (Zetia)

• Intestinal cholesterol absorption inhibitor, further lower LDL
• QD dosing.

 

Bile acid-binding resin

• Drugs: cholestyramine (Questran), colesevelam (Welcol), colestipol (Colestid)
• Welcol was also approved for DM2, with less GI than others. (Pregnancy category C). Others ok in pregnancy.
• Questran is also approved for pruritus caused by partial biliary obstruction, low dose can be used to treat hyperthyroidism (increase fecal excretion of T4).
• SE: constipation/ABD pain/nausea (all these are GI effects due to their action site in the gut), may increase TG and decrease absorption of other drugs (binder).
• CI: bowel obstruction, TG>500, hypertriglyceridemia-induced pancreatitis (may further increase TG).
• DDI
  • Phenytoin, levothyroxine, glyburide, OCP, MVIs
  • warfarin, Niaspan, fenofibrate

Fibrates

• Drugs: gemfibrozil (Lopid), fenofibrate (TriCor, Trilipix)
• MOA: Activate PPARa, enhance elimination and decrease the synthesis of LDL, TG, and increase HDL
• SE: myopathy & rhabdomyolysis (less than statin), increased liver enzymes, abdominal pain.
• Gemfibrozil:600mg BID before breakfast and dinner

 

Niacin (Niaspan, Niacor)

• MOA: Convert to nicotinamide which can inhibit LDL production, increase HDL
• SE: flushing, hyperglycemia, hyperuricemia (careful in gout), hepatotoxicity (very rare).
• Tolerability problem due to flushing/itching. Flushing may subside, pre-treat with ASA, avoid spicy food/alcohol/hot beverage, ER forms less problems.
• Caution with liver disease, gout.
• Take with food, at night (Niaspan)

 

 Lovaza (omega-3 fatty acid)

• Reduce TG synthesis and increase degradation.
• Use when TG > 500.
• SE: taste perversion (fish taste), burping, bleeding risk (warfarin, ASA, clopidogrel).

  

Quiz

1. A patient has been taking simvastatin 40 mg PO at bedtime for 3 weeks and is now complaining of muscle pain. Which of the following laboratory tests should be obtained?
   1. Blood glucose
   2. Simvastatin blood level
   3. Complete blood count
   4. Creatine kinase
   5. Thyroid function tests

 

2. Which of the following statements concerning niacin is TRUE?
   1. It is available over the counter.
   2. It can increase a patient’ s risk for developing hypoglycemia.
   3. Patients should be advised to take acetaminophen 30 minutes before each dose.
   4. The dose should be titrated up on a weekly basis until a daily dose of 3,000 mg is achieved.
   5. It is contraindicated in patients with hypertriglyceridemia. 

 

 

Answers (Click to expand)

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