Fibrates And Hyperlipidemia

  • Shazia AsimMPhil Pharmacology University of Health Sciences Lahore, Pakistan

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What is hyperlipidemia?

Lipids in our body include cholesterol, cholesterol esters, Phospholipids, and triglycerides. Hyperlipidemia is a condition in which there is an increased level of one or more lipids in the system. The abnormalities in the lipoprotein are a major cause of hyperlipidemia.1 The different types of lipoprotein include:

Types of Lipoprotein

  • Chylomicrons are the biggest particles, both in size and density, and their concentration is directly proportional to dietary triglyceride levels.
  • Very low-density lipoproteins are smaller particles that include more chylomicrons than triglycerides and are released by the liver. Very low-density lipoprotein transports sterol from the liver to many organs and tissues in the body. 
  • They are generated by a combination of cholesterol and triglycerides
  • After being lysed by the lipase enzyme in adipose tissue and muscle capillaries, VLDL particles form intermediate-density lipoproteins.
  • Low-density lipoproteins are produced partially in the intestinal chyle and partially through lipolysis of extremely low-density lipoproteins.
  • High-density lipoprotein is also known as good cholesterol. The liver synthesises high-density lipoproteins. It transports cholesterol and lipids from tissues to the liver for breakdown.1 

Classification of Hyperlipidemia

  • The primary cause is also known as familial and can be caused by a genetic abnormality. It can also be monogenic, a single gene defect, or polygenic (many gene errors).  
  • Secondary causes include diabetes, nephritic syndromes, persistent drinking, hypothyroidism, and drug use, such as corticosteroids, beta blockers, and oral contraceptives, which can all lead to the development of this condition.2

Symptoms of Hyperlipidemia

Typically, hyperlipidemia doesn't show any symptoms at first; instead, they are often detected by routine testing or when the condition gets dangerous enough to cause a heart attack or stroke. Patients who have familial variations of the condition or high blood cholesterol levels may develop xanthomas, or cholesterol deposits under the skin, particularly under the eyes. Patients with high triglyceride levels may also experience pimple-like lesions at various body sites.2

Complications of Hyperlipidemia

Increased level of cholesterol and triglycerides is a risk factor for various cardiovascular diseases including:

  • Atherosclerosis
  • Coronary Artery Disease (CAD)
  • Myocardial Infarction (MI)
  • Ischemic stroke. It is important to have routine analysis of cholesterol and triglycerides to prevent hyperlipidemia and its complications

Antihyperlipidemic drugs

  • Statins, 
  • Fibric acid derivatives, 
  • Bile acid binding resins, 
  • Nicotinic acid derivatives and 
  • Drugs that inhibit cholesterol absorption. These are general classifications of antihyperlipidemic drugs.2 Let’s have a discussion about Fibrates and hyperlipidemia in brief.

Fibrates and Hyperlipidemia

Fibrates are a commonly used class of antihyperlipidemic medications that provide a slight reduction in LDL cholesterol and a considerable reduction in plasma triglycerides. The level of HDL cholesterol also rises to some extent. Examples of these agents are:

  • Bezafibrate
  • Gemfibrozil
  • Clofibrate
  • Fenofibrate.2

Mechanism of action

Stimulation of peroxisome proliferator-activated receptor α (PPARα) regulates a wide range of genes related to inflammation, plasma lipoprotein modulation, and cellular lipid balance. 

By controlling the expression of genes involved in several metabolic pathways, fibrates' activation of PPARα lowers serum triglyceride levels and increases HDL cholesterol. Fibrates inhibit the liver's ability to synthesise triglycerides and produce very low-density lipoproteins (VLDL). They control genes related to the absorption and transport of fatty acids as well. The reduction of apolipoprotein (apo) CIII expression by the liver and the stimulation of intravascular lipolysis through PPARα, enhances the production of lipoprotein lipase which constitutes a major mechanism for the triglyceride-lowering actions of fibrates. Lipoprotein lipase is the enzyme that breaks down triglycerides in VLDL and chylomicrons. This process produces leftover lipoproteins, which the liver eliminates. Reduced production of apo CIII encourages the active hydrolysis of triglycerides since it is a natural lipoprotein lipase inhibitor.3

Specific Indication of Fibrates:

  • Primary Hypertriglyceridemia
  • Primary Hypercholesterolemia
  • Combined Hyperlipidemia
  • Type III Dysbetalipoproteinemia
  • Non–Insulin-Dependent Diabetes Mellitus.4

Side effects and contraindications

Usually, fibrates are well tolerated. Urticaria, anaemia, headaches, fatigue, and hair loss are some of the side effects. Gallstones can be brought on by all of the fibrates, which also raise biliary cholesterol concentrations. There have been reports of minor reductions in alkaline phosphatase and minor elevations in liver transaminase enzymes. Patients on fibrates may need to decrease their warfarin dosage by 30% because fibrates remove warfarin from albumin-binding sites. 60% to 90% of an oral dosage of fibrates is eliminated in the urine, primarily as glucuronide conjugates. Fibrate usage is contraindicated in cases of renal insufficiency and Liver dysfunction.2,3

FAQs

What is the difference between fibrates and statins?

Both of these groups are cholesterol-lowering drugs. Statins (eg, atorvastatin, simvastatin)  are used to lower LDL cholesterol levels by inhibiting an enzyme called HMG-CoA reductase. Statins reduce the risk of cardiovascular events like heart attacks and stroke. Fibrates on the other hand primarily target triglyceride levels in the blood and can also increase HDL cholesterol levels. These drugs function by activating a receptor called PPAR-alpha, which regulates the expression of genes involved in lipid metabolism.5

Can we take fibrates and statins together?

The treatment with a fibrate and statin combination offers clinical benefits that are superior to treatment with fibrate alone, but this combination increases the risk of side effects, particularly renal side effects. Therapy should thus be carefully monitored.6

Which group of cholesterol-lowering drugs is considered the most favorite amongst clinicians?

Statins are generally favored by clinicians for lowering cholesterol due to their effectiveness in reducing LDL "bad" cholesterol levels and their documented ability to reduce the risk of cardiovascular events like heart attacks and strokes.7

 Summary

  • Hyperlipidemia is a condition when you have increased levels of plasma cholesterol or triglycerides in your body.
  • It does not show any symptoms hence it is important that you take routine blood analysis to find the disorder.
  • Fibrates are a class of drugs which are used to treat hyperlipidemia.
  • Take these medications only on the advice of your physician.
  • Follow the instructions from your pharmacist and if you find any discomfort or undesirable effects report to your healthcare provider immediately.
  • Try to maintain good lifestyle habits of exercise, diet, and take care of your health!

References

  1. P Mumthaj, P Natarajan, A.M Janani, J Vijay, V Gokul. A global review article on hyperlipidemia. IJPSRR [Internet]. 2021 May 15 [cited 2024 Feb 12];68(1). Available from: https://globalresearchonline.net/journalcontents/v68-1/18.pdf
  2. Shattat GF. A review article on hyperlipidemia: types, treatments and new drug targets. Biomed Pharmacol J [Internet]. 2014 Dec 30 [cited 2024 Feb 12];7(2):399–409. Available from: http://www.biomedpharmajournal.org/absdoic.php?snoid=504
  3. Fazio S, Linton MF. The role of fibrates in managing hyperlipidemia: Mechanisms of action and clinical efficacy. Curr Atheroscler Rep [Internet]. 2004 Mar [cited 2024 Feb 12];6(2):148–57. Available from: http://link.springer.com/10.1007/s11883-004-0104-8
  4. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation [Internet]. 1998 Nov 10 [cited 2024 Feb 12];98(19):2088–93. Available from: https://www.ahajournals.org/doi/10.1161/01.CIR.98.19.2088
  5. Sahebkar A, Serban MC, Mikhailidis DP, Toth PP, Muntner P, Ursoniu S, et al. Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentrations: A systematic review and meta-analysis. Pharmacological Research [Internet]. 2016 Jan 1 [cited 2024 May 20];103:236–52. Available from: https://www.sciencedirect.com/science/article/pii/S1043661815302085
  6. Choi, Hye Duck, et al. “Safety and Efficacy of Fibrate–Statin Combination Therapy Compared to Fibrate Monotherapy in Patients with Dyslipidemia: A Meta-Analysis.” Vascular Pharmacology, vol. 65–66, Feb. 2015, pp. 23–30. ScienceDirect, Available from: https://doi.org/10.1016/j.vph.2014.11.002.
  7. “High Cholesterol Numbers Got You Down?” Cleveland Clinic, Accessed 20 May 2024. Available from: https://my.clevelandclinic.org/health/treatments/antihyperlipidemic.

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Koushika M

Master's degree, Medicinal and Pharmaceutical Chemistry, SRMIST, Kattankulathur, Chennai, Tamil Nadu

Koushika is a freelance writer with strong background in the field of Pharmaceutical Sciences. She has an expertise of combining her medical knowledge with writing and provide reliable health content.

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