DDInter1570 DDInter1675
Chronic angina is a common cardiovascular condition affecting millions worldwide and causes significant disability while interfering with daily activities. Ranolazine is a well-tolerated piperazine derivative used for the management of this condition, offering relief from uncomfortable and debilitating symptoms. With a mechanism of action different from drugs used to treat the same condition, ranolazine is a promising anti-anginal therapy. It was originally approved by the FDA in 2006.
Simvastatin, also known as the brand name product Zocor, is a lipid-lowering drug derived synthetically from a fermentation product of _Aspergillus terreus_. It belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.[A181087, A181406] Simvastatin and other drugs from the statin class of medications including [atorvastatin], [pravastatin], [rosuvastatin], [fluvastatin], and [lovastatin] are considered first-line options for the treatment of dyslipidemia.[A181087, A181406] Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.[A181087,A181553] Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.[A181090,A181093,A181096,A181427,A181475,A181538] Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.[A181087, A181406] Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.[A181397, A181403] While all statin medications are considered equally effective from a clinical standpoint, [rosuvastatin] is considered the most potent; doses of 10 to 40mg [rosuvastatin] per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while simvastatin has been found to have an average decrease in LDL-C of ~35%.[A181409,A181535,A181538,A1793] Potency is thought to correlate to tissue permeability as the more lipophilic statins such as simvastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as [pravastatin] and [rosuvastatin] which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport.[A181424,A181460] Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.
Ranolazine {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) upregulates {v} (Gene) NR1H2
NR1H2 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) downregulates {v} (Gene) MRPS16
MRPS16 {u} (Gene) is downregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) causes {v} (Side Effect) Gastrointestinal pain
Gastrointestinal pain {u} (Side Effect) is caused by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) interacts with {v} (Gene) UGT2B7
UGT2B7 {u} (Gene) is bound by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) binds {v} (Gene) CYP2D6
CYP2D6 {u} (Gene) covaries with {v} (Gene) YRDC
YRDC {u} (Gene) is downregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) upregulates {v} (Gene) NR1H2
NR1H2 {u} (Gene) regulates {v} (Gene) FOXO4
FOXO4 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) upregulates {v} (Gene) DENND2D
DENND2D {u} (Gene) is regulated by {v} (Gene) CDK19
CDK19 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) downregulates {v} (Gene) MRPS16
MRPS16 {u} (Gene) regulates {v} (Gene) ARHGAP1
ARHGAP1 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Ranolazine {u} (Compound) downregulates {v} (Gene) SDHB
SDHB {u} (Gene) is regulated by {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Simvastatin
Ranolazine (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Simvastatin (Compound)
Ranolazine (Compound) upregulates NR1H2 (Gene) and NR1H2 (Gene) is upregulated by Simvastatin (Compound)
Ranolazine (Compound) downregulates MRPS16 (Gene) and MRPS16 (Gene) is downregulated by Simvastatin (Compound)
Ranolazine (Compound) causes Gastrointestinal pain (Side Effect) and Gastrointestinal pain (Side Effect) is caused by Simvastatin (Compound)
Ranolazine (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) interacts with UGT2B7 (Gene) and UGT2B7 (Gene) is bound by Simvastatin (Compound)
Ranolazine (Compound) binds CYP2D6 (Gene) and CYP2D6 (Gene) covaries with YRDC (Gene) and YRDC (Gene) is downregulated by Simvastatin (Compound)
Ranolazine (Compound) upregulates NR1H2 (Gene) and NR1H2 (Gene) regulates FOXO4 (Gene) and FOXO4 (Gene) is upregulated by Simvastatin (Compound)
Ranolazine (Compound) upregulates DENND2D (Gene) and DENND2D (Gene) is regulated by CDK19 (Gene) and CDK19 (Gene) is upregulated by Simvastatin (Compound)
Ranolazine (Compound) downregulates MRPS16 (Gene) and MRPS16 (Gene) regulates ARHGAP1 (Gene) and ARHGAP1 (Gene) is upregulated by Simvastatin (Compound)
Ranolazine (Compound) downregulates SDHB (Gene) and SDHB (Gene) is regulated by ABCB1 (Gene) and ABCB1 (Gene) is bound by Simvastatin (Compound)