Pleural disease induced by drugs
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Only mild adverse events, including rash and diarrhoea, have been reported with vitamin B5. There is an isolated report of a 76-year-old woman who was hospitalized with chest pain and dyspnoea.55 She had no history of atopic disease. She had been taking trimetazidine for 6 years, vitamin H (10 mg daily) and vitamin B5 (300 mg daily) for 2 months for the treatment of alopecia. Chest radiograph showed cardiac enlargement and a pleural effusion. Clinical examination and echocardiogram revealed cardiac tamponade. The absolute pleural fluid eosinophil count ranged from 1200 to 1500/μL. At pericardiectomy the fluid was a sterile exudate with protein 6.7 g/dL with 1500 eosinophils/μL. Histology showed an eosinophilic infiltrate. The pleural fluid also confirmed eosinophilia. Despite multiple thoracenteses the pleural effusion recurred, leading to thoracotomy. All studies for rheumatological disorders, infection and occult malignancy were negative. Vitamins B5 and H were discontinued, and 1 week later the patient improved dramatically with resolution of blood eosinophilia. Trimetazidine was also discontinued but readministered a few months later without symptoms or an increase in eosinophilia. The patient was symptom-free without relapse at a 2-year follow-up visit.
Pathophysiology of Heart Failure with Reduced Ejection Fraction
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
Trimetazidine is a partial inhibitor of 3-ketoacyl CoA thiolase, a key enzyme involved in fatty acid oxidation. Numerous small-scale trials have been conducted, showing variable changes in cardiac function. A meta-analysis of nearly one thousand patients demonstrated improvements in ventricular hemodynamic and clinical outcomes, including exercise capacity, all-cause mortality, and combined cardiovascular events and hospitalization. Although most studies have been limited to ischemic cardiomyopathy, a more recent trial noted improvements in hemodynamic and functional status in non-ischemic cardiomyopathy patients.28
Angina pectoris in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Trimetazidine is an antianginal drug which improves myocardial glucose utilization through inhibition of fatty acid metabolism. A meta-analysis of 13 randomized clinical trials showed that trimetazidine was efficacious in the treatment of patients with stable angina pectoris and reduced the number of weekly anginal episodes, reduced the weekly nitroglycerin use, caused a longer time to 1 mm of ischemic ST-segment depression, increased total work, and caused a longer exercise duration at peak exercise (129).
Hypertrophic cardiomyopathy: an up-to-date snapshot of the clinical drug development pipeline
Published in Expert Opinion on Investigational Drugs, 2022
Juan Tamargo, María Tamargo, Ricardo Caballero
These alterations led to the development of mitotropic drugs that shift cardiac metabolism from fatty acids to glucose that generates more ATP per unit of oxygen consumed, increase myocardial efficiency, and may improve cardiac function in patients with HCM [93,94]. Two antianginal drugs were evaluated: perhexiline, a carnitine palmitoyltransferase-1 inhibitor, and trimetazidine, a long-chain 3-ketoacyl-coenzyme A thiolase inhibitor. But despite the favorable results observed with perhexiline in preclinical [38] and in a phase 2 trial [99], a larger trial (NCT02862600) was prematurely terminated due to lack of efficacy and presence of adverse events. Similarly, trimetazidine was ineffective in improving exercise capacity in symptomatic patients with no-HCM [61]. But despite these negative results, two ongoing trials examine the effects of perhexiline and trimetazidine in HCM (Table 3) [88,89].
5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations
Published in Acta Cardiologica, 2022
Eleftherios Teperikidis, Aristi Boulmpou, Panagiotis Charalampidis, Chalil Tsavousoglou, George Giannakoulas, Christodoulos E. Papadopoulos, Vassilios Vassilikos
Further available options for treating vasospastic angina include nicorandil and fasudil (Class IIa) [63]. Nicorandil is a dual nitrate and ATP-sensitive K channel agonist [66]. We ran a PubMed search using ‘fluorouracil and nicorandil’ which yielded 3 results, 2 of which were case reports where nicorandil was successfully used as part of a multi-drug regimen, including nitrates, in the treatment of 5-FU cardiotoxicities [67,68]. However, nicorandil is not widely available and therefore clinical experience is minor, whilst its use in routine clinical treatment is limited. Fasudil is an intracellular calcium antagonist and a Rho Kinase inhibitor that is approved in Japan and China for the treatment of cerebral vasospasm. Rho kinase is an important mediator of vasoconstriction [69]. Several other potential mechanisms for this molecule have been proposed. While its use in the treatment of vasospasm is classified as Class IIa, we ran a PubMed search using ‘fluorouracil and fasudil’ which yielded no results. Finally, ranolazine and trimetazidine, two broadly used regimens in the treatment of chronic stable angina, may be considered as therapeutic options in 5-FU vasospastic angina. While our search for ‘fluorouracil and ranolazine’ did not produce any results, we were able to locate 1 case report for ‘fluorouracil and trimetazidine’ [70]. In this report, trimetazidine was successfully administered along with CCB and nitrates in a capecitabine re-challenge attempt.
Antinociceptive effect of ranolazine and trimetazidine
Published in Expert Review of Cardiovascular Therapy, 2021
Trimetazidine can be preferred with its low side effect profile in the treatment of patients with persistent angina who are not suitable for percutaneous and surgical revascularization. Trimetazidine (1-2,3,4-trimethoxybenzyl piperazine dihydrochloride), a member of the 3-ketoacyl coenzyme A class of thiolase inhibitors, is a metabolic modulator. It inhibits the β-oxidation of fatty acids; increases myocardial glucose utilization, prevents a decrease in ATP and phosphocreatine levels in response to hypoxia or ischemia; It minimizes free radical production and protects against intracellular calcium overload and acidosis. The most common side effects of trimetazidine are nausea, vomiting, tiredness, dizziness and muscle pain. The drug may increase extrapyramidal stiffness, bradykinesia, and tremor by inducing Parkinson’s symptoms. Although the mechanism responsible for these reactions is unknown, it is thought that trimetazidine is a piperazine derivative and causes such side effects because it causes blockage of central D2 dopamine receptors [16].
Related Knowledge Centers
- Angina
- Blood Pressure
- Coronary Flow Reserve
- Cytoprotection
- Fatty Acid Metabolism
- Heart Rate
- Tinnitus
- Cardiac Muscle
- Iupac Nomenclature of Organic Chemistry
- Fatty Acid Oxidation Inhibitors