Statin Medications Case File

https://medical-phd.blogspot.com/2021/03/statin-medications-case-file.html

Eugene C.Toy, MD, William E. Seifert, Jr., PHD, Henry W. Strobel, PHD, Konrad P. Harms, MD

❖ CASE 34
A 49-year-old female presents to your clinic for follow-up after initiating a new medication (lovastatin) for her
elevated cholesterol. She is currently without complaints and is feeling well. On repeat serum cholesterol
screening, there is noted to be a decrease in the cholesterol level. The patient asks if she needs to continue the
medication and what the potential side effects and benefits might be. Her physician explains that this
medication inhibits the ratelimiting step and key enzyme in cholesterol biosynthesis.

◆ What is the mechanism of action of this medication?

ANSWER TO CASE 34: STATIN MEDICATIONS

Summary: A 49-year-old female with history of elevated cholesterol on lovastatin, which appears to be
improving serum cholesterol levels.

◆ Mechanism action of lovastatin: β-Hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA) reductase

inhibitor.

CLINICAL CORRELATION
Hyperlipidemia is one of the most treatable risk factors of coronary heart disease. Initially, when the fasting
low-density lipoprotein (LDL) cholesterol is measured and found to be elevated, life style modification is
recommended such as dietary adjustments, exercise, and weight loss. The lipids are measured again after a 3- to
6-month interval. If the LDL cholesterol level is again found to be above threshold, then pharmacologic therapy
is entertained. One of the most common medications is a statin agent, acting to inhibit HMG-CoA reductase.
The potential side effects include elevated liver function tests, increased muscle creatine phosphokinase (CPK)
secondary to myopathy and rarely rhabdomyolysis. Other agents that may be considered include bile acid
sequestrants, nicotinic acid, fibric acid, and fish oils.

APPROACH TO CHOLESTEROL SYNTHESIS

Objectives

1. Know about the role of HMG-CoA reductase in cholesterol synthesis.

2. Know the mechanism of action of statin medications.
3. Understand the role of cholesterol on steroid synthesis.
4. Be aware that niacin decreases lipolysis in adipose tissue and verylow-density lipoprotein (VLDL) synthesis
in liver.

Definitions

Cytochrome P450 enzyme system: The cytochromes P450 are mixedfunction oxidases that require both
NADPH and O2. They are involved in a number of reactions in the conversion of lanosterol to cholesterol, as
well as important steps in the synthesis of steroid hormones. Cytochromes P450 are very important in the
detoxification of xenobiotics and in the metabolism of drugs.

HMG-CoA reductase: β-Hydroxy-β-methylglutaryl-CoA reductase; the enzyme that catalyzes the rate-limiting

and committed step in the synthesis of cholesterol. It converts β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) to
mevalonate.

Isoprenoid: Any of a number of hydrophobic compounds derived from the polymerization of isopentenyl

pyrophosphate and its isomer, dimethylallyl pyrophosphate. The isoprene unit is a five-carbon branched
hydrocarbon (2-methyl-1,3-butadiene).

Statin: Any of a number of drugs that competitively inhibit the ratelimiting enzyme in cholesterol biosynthesis,
HMG-CoA reductase.