Volume : 11, Issue : 03, March – 2024

Title:

A SHORT REVIEW ON HMG CoA REDUCTASE INHIBITORS

Authors :

Riyas Mon O.P, Basim Abdul Bari Palliparambil, Muhammad Jameel K.A, Sabah Abdul Nazir, Mohammed Shifan, Muhammed Fayas B

Abstract :

HMG CoA reductase inhibitors are the first line and more effective treatment for the patients with elevated LDL cholesterol level and to prevent high cholesterol associated disease conditions such as coronary artery disease. The purpose of this article is to clarify the mechanism of action, benefits, pharmacokinetics, dose, adverse reaction and indications of statins. They can inhibit the enzyme HMG CoA an enzyme responsible for conversion of HMG CoA (3-hydroxy-3-methylglutaryl-CoA) into mevalonic acid in the pathway of cholesterol biosynthesis. The action of statins results in a reduction in intracellular levels of cholesterol, an increase in expression of hepatic LDL receptor, and enhanced receptor- medicated catabolism and clearance of LDL-Cholesterol from serum. The overall effect is a reduction in triglycerides, low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and total protein with an increase in high density lipoprotein (HDL) level in the body. An overwhelming amount of data that confirm the morbidity and mortality benefit of statin therapy in high-risk CVD conditions have been reported, both in the primary and secondary prevention settings. Within the statin class, atorvastatin is a stronger medication. At 10 mg/day, 40 mg/day, 45 mg/day, and 80 mg/day, atorvastatin reduces LDL cholesterol by 33%, 40%, 45%, and 50–55%, respectively. Among the medications in the statin class, atorvastatin is the most effective. When compared to other statins, this more recent and well-liked one has the strongest LDL-lowering activity. Moreover, its plasma half-life is longer. Muscle aches, changes in liver function tests, and digestive issues are the most frequent side effects of statin medication. Hepatitis, sleeplessness, nightmares, rashes, and concentration problems are less frequent. These statins showed the best tolerability and hazard profile when it comes to discontinuations because of adverse events, myalgia, transaminase elevations, and CK elevations. The only significant reaction is myopathy, which is uncommon. When compared to other conditions, headaches and digestive problems are typically minor. Clinicians have long utilized statin medicines to treat hypercholesterolemia, hyperlipoproteinemia, and hypertriglyceridemia in addition to diet and exercise.
Keywords: HMG CoA reductase inhibitors, statins, anti-hyperlipidemic agent, Cholesterol lowering agents, Lipid lowering agents.

Cite This Article:

Please cite this article in press Riyas Mon O.P et al., A Short Review on HMG CoA Reductase Inhibitors., Indo Am. J. P. Sci, 2024; 11 (03).

Number of Downloads : 10

References:

[1]. Josan K, Majumdar SR, McAlister FA. The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. Canadian Medical Association Journal. 2008 Feb 26;178(5):576–84.
[2]. Tonelli M, Lloyd A, Clement F, Conly J, Husereau D, Hemmelgarn B, et al. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. CMAJ : Canadian Medical Association Journal [Internet]. 2011 Nov 8 [cited 2021 Nov 7];183(16):e1189–202. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216447/
[3]. Ridker PM, Danielson E, Fonseca FA, et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
[4]. 1.Sidhu G, Sapra A. Pravastatin [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551621/#:~:text=Pravastatin%20is%20a%20medication%20used
[5]. Deedwania P, Lardizabal. Benefits of statin therapy and compliance in high-risk cardiovascular patients. Vascular Health and Risk Management. 2010 Sep;843.
[6]. Lippincott’s Illustrated Reviews, Pharmacology 5th edition, chapter 21: Hyperlipidemias, page no.269
[7]. Essentials of medical pharmacology by KD Tripathi, seventh edition, page no. 637.
[8]. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization.
[9]. Anssi J. H. Mykkänen, Suvi Taskinen, Mikko Neuvonen, Paile‐Hyvärinen M, E. Katriina Tarkiainen, Tuomas Lilius, et al. Genomewide Association Study of Simvastatin Pharmacokinetics. Clinical Pharmacology & Therapeutics. 2022 Jun 24;112(3):676–86.
[10]. 1.McIver LA, Siddique MS. Atorvastatin [Internet]. Nih.gov. StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430779/
[11]. Kanukula R, Salam A, Rodgers A, Kamel B. Pharmacokinetics of Rosuvastatin: A Systematic Review of Randomised Controlled Trials in Healthy Adults. Clinical Pharmacokinetics. 2021 Jan 11;
[12]. 1.Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: A Review of the Pharmacology and Clinical Effectiveness in Cardiovascular Disease. Clinical Medicine Insights: Cardiology [Internet]. 2012 Jan;6(17-33):CMC.S4324. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303484/
[13]. 1.Hui CK, Cheung Y, Lau K. Pharmacokinetics of pitavastatin in subjects with Child‐Pugh A and B cirrhosis. British journal of clinical pharmacology (Print) [Internet]. 2005 Jan 20 [cited 2024 Apr 8];59(3):291–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884781/
‌[14]. Clinical pharmacy and therapeutics by Roger Walker and Cate Whittlesea, 5th edition, page No. 404
[15]. 1.Naci H, Brugts J, Ades T. Comparative Tolerability and Harms of Individual Statins. Circulation: Cardiovascular Quality and Outcomes. 2013 Jul;6(4):390–9.
‌[16]. 1.Ezad S, Cheema H, Collins N. Statin-induced rhabdomyolysis: a complication of a commonly overlooked drug interaction. Oxford Medical Case Reports. 2018 Mar 1;2018(3).
[17]. Strilchuk L, Tocci G, Fogacci F, Cicero AFG. An overview of rosuvastatin/ezetimibe association for the treatment of hypercholesterolemia and mixed dyslipidemia. Expert Opin Pharmacother. 2020 Apr;21(5):531-539. [PubMed]
[18]. Koopal C, Marais AD, Visseren FL. Familial dysbetalipoproteinemia: an underdiagnosed lipid disorder. Curr Opin Endocrinol Diabetes Obes. 2017 Apr;24(2):133-139. [PubMed]
[19]. van Rosendael AR, van den Hoogen IJ, Gianni U, Ma X, Tantawy SW, Bax AM, Lu Y, Andreini D, Al-Mallah MH, Budoff MJ, Cademartiri F, Chinnaiyan K, Choi JH, Conte E, Marques H, de Araújo Gonçalves P, Gottlieb I, Hadamitzky M, Leipsic JA, Maffei E, Pontone G, Shin S, Kim YJ, Lee BK, Chun EJ, Sung JM, Lee SE, Virmani R, Samady H, Sato Y, Stone PH, Berman DS, Narula J, Blankstein R, Min JK, Lin FY, Shaw LJ, Bax JJ, Chang HJ. Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition. JAMA Cardiol. 2021 Nov 01;6(11):1257-1266. [PMC free article] [PubMed]
[20]. Rygiel K. Hypertriglyceridemia – Common Causes, Prevention and Treatment Strategies. Curr Cardiol Rev. 2018 Mar 14;14(1):67-76. [PMC free article] [PubMed]
[21]. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143. [PMC free article] [PubMed]
[22]. Amarenco P, Tonkin AM. Statins for stroke prevention: disappointment and hope. Circulation. 2004 Jun 15;109(23 Suppl 1):III44-9. [PubMed]
[23]. Luirink IK, Wiegman A, Kusters DM, Hof MH, Groothoff JW, de Groot E, Kastelein JJP, Hutten BA. 20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia. N Engl J Med. 2019 Oct 17;381(16):1547-1556. [PubMed]
[24]. McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB. Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia. J Am Heart Assoc. 2019 Dec 17;8(24):e013225. [PMC free article] [PubMed]
[25]. O’Malley PG, Arnold MJ, Kelley C, Spacek L, Buelt A, Natarajan S, Donahue MP, Vagichev E, Ballard-Hernandez J, Logan A, Thomas L, Ritter J, Neubauer BE, Downs JR. Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Ann Intern Med. 2020 Nov 17;173(10):822-829. [PubMed]
[26]. Research C for DE and. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. FDA [Internet]. 2019 Jun 18; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-restrictions-contraindications-and-dose-limitations-zocor.
[27]. 1.UpToDate [Internet]. Uptodate.com. 2020. Available from: https://www.uptodate.com/contents/statins-actions-side-effects-and-administration
[28]. 1.Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology [Internet]. 2007 Aug 28 [cited 2021 Nov 5];69(9):904–10. Available from: https://pubmed.ncbi.nlm.nih.gov/17724294/