Lipid-lowering medications: Statins

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Lipid-lowering medications: Statins

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USMLE® Step 2 style questions USMLE

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A 45-year-old man presents to the office for a routine follow-up. He has been feeling healthy and has no concerns. Past medical history is significant for type II diabetes mellitus and hypertension. Current medications include metformin and lisinopril. Family history is significant for myocardial infarction in his father. The patient smokes a pack of cigarettes daily but does not consume alcohol or illicit substances. Temperature is 37.0°C (98.6°F), pulse is 90/min, respirations are 17/min, and blood pressure is 125/82 mmHg. Physical examination shows a well-appearing male with no abnormal findings. Laboratory testing is obtained, and the results are shown below. Which of the following is the most appropriate next step in the management of this patient?  

Laboratory Value
Results
Low-density lipoproteins (LDL)
190 mg/dL
High-density lipoprotein (HDL)
35 mg/dL
Triglyceride (TG)
100 mg/dL
Hemoglobin A1c
6.4%
Serum creatinine
1.2 mg/dL

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Statins lower overall lipid levels in the body, and work by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting step of cholesterol metabolism.

They are an incredibly important class of medications because they’ve been shown to decrease complications associated with cardiovascular disease like strokes, heart attacks, and peripheral vascular disease.

Although it’s got a bad reputation, cholesterol is actually a critical component of our cells and is used to build the cell membrane.

It also has other uses like the synthesis of steroid hormones, vitamin D, and bile. Normally, we get our cholesterol from the food we eat, but it can also be synthesized by the liver.

So when we eat a box of chili fries, the fats and cholesterol are absorbed in the small intestine. However, they’re not water soluble, so they can’t travel freely in the blood.

To fix this, our body makes shipping boxes called lipoproteins.

These containers consist of a shell made of phospholipids and protein tags that act as instructions for their destination.

So after absorption, the small intestinal cells package the fats and cholesterol into the largest but least dense lipoproteins, called chylomicrons.

These are released into the lymphatic system and then enter the bloodstream via the subclavian vein. Then they travel through the blood to reach adipose tissue and the liver.

Now, the liver can also synthesize intrinsic cholesterol through the mevalonate pathway, which happens in the smooth endoplasmic reticulum of liver cells.

It begins with 2 acetyl-CoA molecules getting joined together by the enzyme acetyl-CoA acyl-transferase.

The result is a 4-carbon molecule called acetoacetyl-CoA.

Next, the enzyme HMG-CoA synthase combines acetoacetyl-CoA and acetyl-CoA to form a 6-carbon molecule called 3-hydroxy-3-methylglutaryl CoA, or HMG-CoA.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Statin-induced myopathies" Pharmacological Reports (2011)
  5. "Pleiotropic Effects of Statins on the Cardiovascular System" Circulation Research (2017)
  6. "Statins: mechanism of action and effects" Journal of Cellular and Molecular Medicine (2001)
  7. "Diagnosis and Management of Statin Intolerance" Journal of Atherosclerosis and Thrombosis (2019)
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