DDInter416 DDInter1675
This drug is a broad spectrum antimycotic or antifungal agent. Clotrimazole's antimycotic properties were discovered in the late 1960s. Clotrimazole falls under the _imidazole_ category of _azole_ antifungals, possessing broad-spectrum antimycotic activity. It is available in various preparations, including creams, pessaries, and troche formulations (slowly dissolving tablets). As well as its antifungal activity, clotrimazole has become a drug of interest in treating several other diseases such as sickle cell disease, malaria and some cancers. The minimal side effect profile of this drug and its uncomplicated metabolic profile have led it to gain widespread acceptance for the treatment of mycotic outbreaks such as vaginal yeast infections as well as athlete's foot.
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.
Clotrimazole {u} (Compound) binds {v} (Gene) ABCC2
ABCC2 {u} (Gene) is bound by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) upregulates {v} (Gene) PCK2
PCK2 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) causes {v} (Side Effect) Nausea
Nausea {u} (Side Effect) is caused by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) ABCC2
ABCC2 {u} (Gene) regulates {v} (Gene) FOXO4
FOXO4 {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) interacts with {v} (Gene) UGT2B7
UGT2B7 {u} (Gene) is bound by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Dapagliflozin
Dapagliflozin {u} may cause a minor interaction that can limit clinical effects when taken with {v} Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP2D6
CYP2D6 {u} (Gene) covaries with {v} (Gene) YRDC
YRDC {u} (Gene) is downregulated by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) interacts with {v} (Gene) BLMH
BLMH {u} (Gene) is downregulated by {v} (Compound) Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP3A7-CYP3A51P
CYP3A7-CYP3A51P {u} (Gene) is bound by {v} (Compound) Atorvastatin
Atorvastatin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Simvastatin
Clotrimazole {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is associated with {v} (Disease) coronary artery disease
coronary artery disease {u} (Disease) is treated by {v} (Compound) Simvastatin
Clotrimazole (Compound) binds ABCC2 (Gene) and ABCC2 (Gene) is bound by Simvastatin (Compound)
Clotrimazole (Compound) upregulates PCK2 (Gene) and PCK2 (Gene) is upregulated by Simvastatin (Compound)
Clotrimazole (Compound) causes Nausea (Side Effect) and Nausea (Side Effect) is caused by Simvastatin (Compound)
Clotrimazole (Compound) binds ABCC2 (Gene) and ABCC2 (Gene) regulates FOXO4 (Gene) and FOXO4 (Gene) is upregulated by Simvastatin (Compound)
Clotrimazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) interacts with UGT2B7 (Gene) and UGT2B7 (Gene) is bound by Simvastatin (Compound)
Clotrimazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Dapagliflozin (Compound) and Dapagliflozin may cause a minor interaction that can limit clinical effects when taken with Simvastatin
Clotrimazole (Compound) binds CYP2D6 (Gene) and CYP2D6 (Gene) covaries with YRDC (Gene) and YRDC (Gene) is downregulated by Simvastatin (Compound)
Clotrimazole (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) interacts with BLMH (Gene) and BLMH (Gene) is downregulated by Simvastatin (Compound)
Clotrimazole (Compound) binds CYP3A7-CYP3A51P (Gene) and CYP3A7-CYP3A51P (Gene) is bound by Atorvastatin (Compound) and Atorvastatin may cause a moderate interaction that could exacerbate diseases when taken with Simvastatin
Clotrimazole (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is associated with coronary artery disease (Disease) and coronary artery disease (Disease) is treated by Simvastatin (Compound)