The relationship between cholesterol and cardiac complications has rendered the metabolism of the steroid compound important among medical practitioners. Despite the common myth that cholesterol is wrong, the body requires the compound in the synthesis of hormones and also the active form of vitamin D (Rosenson, 2012). Excess cholesterol in the blood combines with other substances to form insoluble masses that clog arteries leading to coronary artery disease.
However, cholesterol is categorized into three main groups depending on the function. Low-density lipoprotein is commonly referred to as bad cholesterol as it has a high affinity to binding to blood substances leading to plaques which lead to coronary disorders. Goldstein and Brown (1973) conducted a study on the homeostasis of cholesterol paving the way for the development of several cholesterol-lowering therapies that are still in use today. The paper will discuss and contrast statin and resin therapies in the reduction of cholesterol.
Delegate your assignment to our experts and they will do the rest.
Statins are compounds that inhibit the action of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Statins are considered to be the most efficient drugs in the control of plasma cholesterol. Mevalonate, the compound that results due to the action of HMG-CoA reductase action, is a precursor to cholesterol; hence its inhibition leads to decreased cholesterol synthesis.
According to Stancu and Sima (2001), statins act in two primary mechanisms, i.e., mechanisms involving lipids and mechanisms involving intracellular signaling pathways. Looking into the first mechanism, statins target hepatocytes and inhibit the action of HMG-CoA reductase; the enzyme used to convert HMG-CoA into mevalonic acid. As initially stated, mevalonic acid, also called mevalonate, is the precursor of cholesterol formation. Statins inhibit the HMG-CoA reductase enzyme by not only binding to the enzyme’s active sites but also alter the formation of the enzyme preventing it from attaining a functional structure.
The change in the structure makes the drug very effective and specific. The reduction in mevalonic acid in the liver increases the gene expression for LDL receptors which reduce the cholesterol in the blood by binding the LDL-cholesterol flowing in the blood. Stance and Sima (2001) further report that all statins reduce LDL cholesterol dose-dependently after the administration of a single daily dose. Resin is a drug in the group of bile acid sequestrants. These types of drugs work in conjunction with dietary modifications hence are not as effective when compared to the statins.
The bile acid sequestrants mode of action occurs in the GIT. The drugs bind the bile acids in the intestines and increase the excretion of the bile acids in the stool. This reduces the amount of bile acids being reabsorbed back to the liver, thus forcing the liver to produce more bile to replace the one lost. Bile acids are a product of cholesterol; thus, the liver converts more cholesterol into bile acids which in turn reduces the level of LDL-cholesterol in the blood. Einarsson et al. (1991) report that bile acid sequestrants are most useful in combination with other cholesterol-lowering therapies. This combination nature renders bile acid sequestrants less effective and efficient in reducing blood cholesterol when compared to statin’s mode of action.
Despite the positive effects of the drugs, several unique side effects to each therapy have been reported. Stancu and Sima (2001) report that despite the commendable tolerance of statins, they can lead to liver and muscle toxicity. This mainly occurs when statins are administered with other drugs that inhibit their action, leading to increased concentration of statins in the blood. These elevated levels have been known to cause myopathy. Other risk factors include hepatic dysfunction, renal insufficiency, and hypothyroidism. Bile acid sequestrants have side effects that occur in the gastrointestinal tract due to their mode of action. Common reported effects of bile acid sequestrants include constipation, abdominal pain, bloating, flatulence, diarrhea, heartburn, weight loss and I severe cases, gallstones.
References
Einarsson, K., Ericsson, S., Ewerth, S., Reihner, E., Rudling, M., Ståhlberg, D., & Angelin, B. (1991). Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism. European journal of clinical pharmacology , 40 (1), S53-S58.
Goldstein, J. L., & Brown, M. S. (1973). Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proceedings of the National Academy of Sciences , 70 (10), 2804-2808.
Rosenson, R. S. (2012). Statins: actions, side effects, and administration. UpToDate® Online , 19 .
Stancu, C., & Sima, A. (2001). Statins: mechanism of action and effects. Journal of cellular and molecular medicine , 5 (4), 378-387.
