Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none?

Mezincescu, Alice; Karthikeyan, Vellore J; Nadar, Sunil

doi:10.18295/squmj.2018.18.01.003

Cited by 8 publications

(5 citation statements)

References 73 publications

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“…4 Ranolazine affects cardiac late phase sodium channels as well as β-adrenoceptors and L-type calcium channels at higher concentrations. 5 The elimination half-life of ranolazine ER is ~7 hours, and steady state is obtained within 3 days of twice-daily dosing. 2 Cobicistat is a strong CYP3A4 inhibitor, whereas darunavir moderately inhibits CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

Unrecognized Drug Interaction: Ranolazine Adverse Effects Intensified by Darunavir-Cobicistat

Dougherty¹,

Wynn²,

Maarsingh³

2019

Ann Pharmacother

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Antiretroviral drug interactions and subsequent safety problems are not always identified. This case report describes a patient who suffered from severe adverse drug effects from the interaction between ranolazine ER and darunavir-cobicistat (Prezcobix ®), a drug combination that is contraindicated. 1 After adding ranolazine to darunavircobicistat, the patient exhibited increased and persistent episodes of nausea, vomiting, dyspepsia, anorexia, and dizziness. These ranolazine adverse effects are described at therapeutic doses, but were enhanced from the drug interaction. 2 The interaction was not identified during ranolazine's initial prescribing and outpatient dispensing. The patient was admitted 3 times at another hospital for similar symptomatology, but ranolazine was continued. In early January 2019, a 64-year-old man was admitted to the hospital with left-sided chest pain, dizziness, and near syncope. The patient had persistent and more severe episodes of nausea, vomiting, dyspepsia, and anorexia for over 2 months, which led to a 9-kg weight loss. Electrocardiography revealed first-degree atrioventricular (AV) block (PR interval 0.232 s) but was negative for ischemia. A computed tomography scan of the head was negative, and an echocardiogram showed a left ejection fraction of 55% to 60%. Laboratory data, including troponin-T levels, were within normal limits, except for a slight decrease in some complete

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Section: Discussionmentioning

confidence: 99%

Unrecognized Drug Interaction: Ranolazine Adverse Effects Intensified by Darunavir-Cobicistat

Dougherty¹,

Wynn²,

Maarsingh³

2019

Ann Pharmacother

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“…As a consequence, ranolazine improves Ca 2+ handling and ameliorates impaired myocardial relaxation and diastolic dysfunction [ 223 ]. Ranolazine also inhibits fatty acid oxidation and improves the efficiency of glucose oxidation [ 224 ]. Experimental studies have demonstrated that ranolazine improved cardiac remodeling as well as systolic and diastolic function by restoring Ca 2+ handling in HF animal models [ 225 ].…”

Section: Emerging Treatment Targeting Specific Mechanisms Of Diabetic...mentioning

confidence: 99%

Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice

et al. 2023

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Diabetic cardiomyopathy is characterized by abnormal myocardial structure or performance in the absence of coronary artery disease or significant valvular heart disease in patients with diabetes mellitus. The spectrum of diabetic cardiomyopathy ranges from subtle myocardial changes to myocardial fibrosis and diastolic function and finally to symptomatic heart failure. Except for sodium–glucose transport protein 2 inhibitors and possibly bariatric and metabolic surgery, there is currently no specific treatment for this distinct disease entity in patients with diabetes. The molecular mechanism of diabetic cardiomyopathy includes impaired nutrient-sensing signaling, dysregulated autophagy, impaired mitochondrial energetics, altered fuel utilization, oxidative stress and lipid peroxidation, advanced glycation end-products, inflammation, impaired calcium homeostasis, abnormal endothelial function and nitric oxide production, aberrant epidermal growth factor receptor signaling, the activation of the renin–angiotensin–aldosterone system and sympathetic hyperactivity, and extracellular matrix accumulation and fibrosis. Here, we summarize several important emerging treatments for diabetic cardiomyopathy targeting specific molecular mechanisms, with evidence from preclinical studies and clinical trials.

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“…The presence of a large number of metabolites (more than 40) makes an additional contribution to the multitargeting of the drug. [244,245]…”

Section: Ranolazinementioning

confidence: 99%

Multitargeting in cardioprotection: An example of biaromatic compounds

Mokrov

2023

Archiv der Pharmazie

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A multitarget drug design approach is actively developing in modern medicinal chemistry and pharmacology, especially with regard to multifactorial diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. A detailed study of many well‐known drugs developed within the single‐target approach also often reveals additional mechanisms of their real pharmacological action. One of the multitarget drug design approaches can be the identification of the basic pharmacophore models corresponding to a wide range of the required target ligands. Among such models in the group of cardioprotectors is the linked biaromatic system. This review develops the concept of a “basic pharmacophore” using the biaromatic pharmacophore of cardioprotectors as an example. It presents an analysis of possible biological targets for compounds corresponding to the biaromatic pharmacophore and an analysis of the spectrum of biological targets for the five most known and most studied cardioprotective drugs corresponding to this model, and their involvement in the biological effects of these drugs.

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Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none?

Cited by 8 publications

References 73 publications

Unrecognized Drug Interaction: Ranolazine Adverse Effects Intensified by Darunavir-Cobicistat

Unrecognized Drug Interaction: Ranolazine Adverse Effects Intensified by Darunavir-Cobicistat

Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice

Multitargeting in cardioprotection: An example of biaromatic compounds

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