Hyperlipidemia is a diagnostic syndrome that is characterized by abnormally high levels of lipids or lipoproteins in the blood. The syndrome itself is a rather common phenomenon and is mostly asymptomatic. Though, hyperlipidemia is a risk factor for the development of numerous diseases, causing systemic atherosclerotic impairment in the body. The latter plays a key role in the development of myocardial infarction, coronary heart disease, chronic cerebrovascular disease, stenosis of the renal arteries and gangrenous lesions of the limbs; it is also the leading cause of death and disability in individuals of older age. Statins or HMG CoA reductase inhibitors are widely prescribed drugs for the treatment of hypercholesterolemia. Statins inhibit HMG-CoA reductase- key rate-limiting enzyme of the cholesterol biosynthetic pathway in the liver. When liver production of cholesterol falls, the levels of cholesterol in the blood also decrease. However, the use of statins as a treatment of hyperlipidemia is accompanied by various side effects. Firstly, due to the suppression of cholesterol synthesis in the liver, the cytoplasmic membranes of hepatocytes are damaged, as they lack cholesterol in their liquid crystal matrix. Some studies have shown the negative effect of statins on the systems in the body with intensively dividing cells, such as the skin, GI mucosa, vascular walls, articular surfaces and muscles. This adverse effect is the cause behind symptoms like flatulence, dyspepsia and abdominal pain due to microerosive lesions of the GI tract mucosa, and constipation often experienced by individuals taking statins. The most dangerous side effect of statins is a specific myopathy, the most severe form of which is rhabdomyolysis. Besides that, statins reduce the levels of ubiquinone (coenzyme Q10), which is a key element playing a unique role in the electron transport chain in mitochondria – it serves as a mobile messenger link between the various enzymes of the chain. Decreased levels of ubiquinone leads to the inhibition of oxidative phosphorylation, required for normal functioning of skeletal muscles and myocardium. In addition, ubiquinone is a powerful and versatile antioxidant that boosts the body’s own supply of antioxidants and prevents free radical damage. Statins’ adverse effects contribute to poor adherence to medication among patients leading to increased morbidity and death (1).
PCSK9 (proprotein convertase subtilisin-like/kexin type 9) is a newly-identified circulating protein in cholesterol metabolism in mammals. It was found that the PCSK9 gene provides instructions for making a protein helping in regulation of the amount of cholesterol in the bloodstream. Loss-of-function PCSK9 mutations result in lower LDL-C levels. Specific pharmacological inhibitors of PCSK9 have demonstrated a significant impact on plasma LDL-C concentrations. Their hypocholesterolemic mechanism of action is based on blocking the activity of PCSK9 with monoclonal antibodies that allows to reduce the degradation of LDL receptors and, therefore, lowers the levels of LDL cholesterol (2).
Resins or bile acid sequestrants (BASs) are a group of drugs used to reduce cholesterol in combination with other hyperlipidemic therapy. Questran or cholestyramine is an example of bile acid sequestrants. It binds bile in the gastrointestinal tract to prevent its reabsorption. This is a strong anion exchange resin, meaning that it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. With normal tolerability, Questran can be used for long-term therapy in combination with statins (3).
As a result of the circulation of bile acids in the digestive system, BASs are excreted into the duodenum, the process of their reabsorption (not absorption) takes place in the intestine, leaving all valuable substances in the body. Because BASs are not absorbed into the blood they have minimal side effects and for that reason can be used by pregnant or lactating women, as well as children and adolescents to treat familial hypercholesterolemia – an inherited disorder with causing high cholesterol levels and leading to aggressive and premature cardiovascular disease