Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.
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PMID:Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. 0 4

We sought to define the current standard of care for children undergoing sedation for painless diagnostic procedures by sending questionnaires to 284 pediatric residency program directors in North America. From the 89 responses, we determined that departments of pediatrics set sedation policies for children in most institutions, often with formal written guidelines for these procedures. Most require that children have some form of cardiorespiratory monitoring while under sedation and that they are attended by individuals trained in cardiorespiratory resuscitation until the child is fully recovered. The use of parents to transport and monitor the sedated child is uncommon, and total lack of monitoring is rare. Chloral hydrate in dosages of 25 mg/kg to 100 mg/kg is the most common drug used for sedation; DPT, a combination of parenteral Demerol (meperidine), Phenergan (promethazine), and Thorazine (chlorpromazine), at a maximum dose of 2 mg/1 mg/1 mg/kg is the second; and pentobarbital in a dosage of 5 mg/kg to 7 mg/kg is the third. These sedation regimens were associated with few serious side effects, except that two deaths were reported in infants with congenital heart disease who were sedated with DPT. We believe this survey may reflect the current standard of practice for sedation in North American infants and children undergoing diagnostic procedures.
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PMID:Sedation of children for technical procedures: current standard of practice. 154 84

Oxipurinol [alloxanthine, Oxyprim, oxypurinol] is the active metabolite of the only commercially available xanthine oxidase inhibitor, allopurinol. Oxipurinol is also a xanthine oxidase inhibitor. Oxipurinol is currently being developed by Cardiome Pharma. It is waiting for approval in the US for the treatment of allopurinol-intolerant hyperuricaemia (gout) and is in phase III trials for the treatment of congestive heart failure. Allopurinol is indicated for the treatment of symptomatic hyperuricaemia, or gout. Approximately 3-5% of patients receiving allopurinol develop intolerance to the drug. Oxipurinol was originally developed by Burroughs Wellcome (later GlaxoSmithKline), and has been available on a compassionate-use basis since 1967 for use in allopurinol-intolerant patients. The licensee company ILEX Oncology has stated that oxipurinol does not have patent protection. Oxipurinol's potential for treatment of congestive heart failure is based on the possibility that xanthine oxidase inhibitors may improve myocardial work efficiency by sensitising cardiac muscle cells to calcium ions, which are a key determinant of cardiac muscle function. This results in more efficient contraction of cardiac muscle cells, without the same increase in oxygen demand. At the second annual BioPartnering North America conference (BPN-2004) [February 2004, Vancouver, Canada], Cardiome Pharma stated that it was seeking a commercialisation partner to market and distribute oxipurinol in the US for the treatment of allopurinol-intolerant hyperuricaemia. In 1995, ILEX Oncology obtained an exclusive licence to oxipurinol from Burroughs Wellcome. Burroughs Wellcome later became part of Glaxo Wellcome, which merged with SmithKline Beecham in December 2000 to form GlaxoSmithKline. ILEX's licence agreement is now with GlaxoSmithKline and The Wellcome Foundation. In December 2001, ILEX granted Paralex, a privately held New York-based company, an exclusive sublicence to all of ILEX's rights to oxipurinol for the treatment of hyperuricaemia in allopurinol-intolerant patients. Paralex additionally gained the right to develop and commercialise oxipurinol in all fields, under data and technology owned by ILEX. Furthermore, Paralex had licensed certain intellectual property rights from The John Hopkins University relating to cardiovascular applications of xanthine oxidase inhibitors. Paralex was acquired by Cardiome Pharma in March 2002. Cardiome Pharma announced early in May 2002 that it had exercised its option to acquire from ILEX Oncology Inc. rights to clinical trial data for oxypurinol for the treatment of gout in allopurinol-intolerant patients. ILEX completed its open-label phase II clinical study of Oxyprim in allopurinol-intolerant gout patients, and the trial data were transferred to Cardiome. Cardiome stated in May 2002 that it intended to commence a further phase II trial of oxypurinol in gout. Phase III trials were in progress in 2003 in this indication. In 1995, ILEX Oncology continued the compassionate use distribution of oxipurinol while establishing a US FDA-approved registration plan for the agent. In November 1998, ILEX received Orphan Drug status for the use of oxipurinol in patients with symptomatic hyperuricaemia. ILEX Oncology's Development Pipeline for 1998 stated that oxipurinol had entered phase II clinical trials for the treatment of hyperuricaemia. In 2001, the clinical trials listing service CenterWatch stated that oxipurinol was in a phase II clinical trial with ILEX Oncology for the treatment of symptomatic hyperuricaemia in patients who are intolerant to allopurinol. The trial appeared to be taking place in the US, and was a multicentre, open-label, 14-week study in 90 patients. In February 2003, Cardiome confirmed beginning patient enrollment in three smaller phase II studies, with the first trial (EXOTIC) now completed. These three smaller proof-of-concept studies will observe surrogate endpoints such as cardiac output and exercise tolerance. The second proof-of-concept study in patients with CHF of ischemic aetiology (IV), known as EXOTIC-EF (Evaluation of XanThine Oxidase Inhibition on Cardiac Ejection Fraction), will assess the effects of oxypurinol on left ventricular performance. The EXOTIC-EF trial will start in the first quarter of 2004 and be completed by the second quarter of 2004. The third, LA PLATA, proof-of-concept study will explore the effects of 1 month of oral oxypurinol therapy on exercise capacity and left ventricular performance. It is projected that the LA PLATA study will start in the first quarter of 2004 and be completed by the third quarter of 2004. During the Heart Failure Society of America's meeting on 21 September 2003, Cardiome presented clinical data from its first proof-of-concept EXOTIC (European Xanthine Oxidase Inhibitors Trial In Cardiac Disease) study. Cardiome intends to conduct a second trial, at the Eppendorf Clinic at the University of Hamburg, to determine the effect of oxypurinol on left ventricular performance in patients with CHF of ischaemic aetiology. This study will be an extension of the original proof-of-concept study. According to the 1st Annual BioPartnering conference held in Vancouver, Canada, in February 2003, Cardiome is seeking co-development partners for oxipurinol in the treatment of congestive heart failure. In July 2003, the US Patent and Trademark Office issued a new patent providing additional protection to Cardiome's programme focused on treatment of congestive heart failure with oxypurinol. The patent, No. 6,569,862, was the second issued to the Johns Hopkins University (JHU) in this field. The key claims in the new patent cover use of the entire family of drugs known as xanthine oxidase inhibitors applied to contractile disorders of the heart, including congestive heart failure. An earlier patent issued to JHU contained provisions relating to a specific mechanism of action and to specific forms of heart disease. Both patents and related intellectual property are licensed exclusively to Cardiome.
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PMID:Oxipurinol: alloxanthine, Oxyprim, oxypurinol. 1513 81

Aldosterone is a mineralocorticoid primarily produced in the zona glomerulosa of the adrenal gland. For many years, aldosterone (Aldo) was thought to have its sole site of action in the kidney, where it regulated sodium excretion and potassium reabsorption. It is now known that Aldo is produced in cardiovascular tissues, and has been implicated in the development of ventricular hypertrophy and cardiac fibrosis. The precise mechanisms whereby Aldo acts in cardiac tissues are diverse. It was assumed that Aldo production could be limited by angiotensin-converting enzyme (ACE) inhibition, but serial measurements during therapy reveal only a transient decrease in Aldo levels. Moreover, the effects of Aldo on cardiac tissues occur even when angiotensin II (Ang II) has been suppressed or eliminated. Multiple investigators have examined effects of Aldo receptor blockade in human subjects and various animal models using the two Aldo receptor antagonists (ARAs), spironolactone and eplerenone. Major clinical trials involving spironolactone (RALES) and eplerenone (EPHESUS) ARAs have shown significant benefits in the treatment of congestive heart failure (CHF). In RALES, patients with New York Heart Association (NYHA) Class III or IV systolic heart failure treated with spironolactone had a 30% relative risk decrease in mortality. Although spironolactone is an effective competitive inhibitor of the mineralocorticoid receptor (MR), progestational and antiandrogenic side effects limit its use in some patients. Eplerenone, a more selective ARA, lacks these undesirable side effects. Although eplerenone is 20-fold less potent at the MR, it demonstrates efficacy similar to spironolactone, possibly due to decreased protein binding. Eplerenone has fewer side effects than spironolactone, which has been attributed to the low cross-reactivity with androgen and progesterone receptors. In EPHESUS, patients with left ventricular systolic dysfunction [Ejection Fraction (EF) <40%] and CHF following an acute myocardial infarction (AMI), were treated with eplerenone, resulting in a 17% reduction in cardiovascular mortality. However, these studies were limited in that diastolic function was not evaluated, although approximately 1/2 of CHF is due to diastolic dysfunction alone. To date, neither ARA has been studied for the treatment of diastolic dysfunction in a major clinical trial. However, numerous animal studies employing ARAs have shown a decrease in cardiac hypertrophy and fibrosis, indicating the potential benefits of these agents in the treatment of diastolic heart failure. In this review, we discuss possible underlying mechanisms responsible for Aldo effects on cardiovascular function and compare the beneficial effects of spironolactone and eplerenone in the treatment of heart disease.
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PMID:Aldosterone receptor antagonists and cardiovascular disease: do we need a change of the guard? 1661 Oct 48

Pulmonary Hypertension (PH) related to Left Heart Disease (LHD) is the most common form of PH, accounting for more than two third of all PH cases. The hemodynamic abnormalities seen in PHLHD are complex, and there are currently minimal evidence-based recommendations for the management of PH-LHD. While it is accepted that PH in the context of left heart disease is a marker of worse prognosis, it remains unclear whether its primary treatment is beneficial or harmful. In this article, we discuss the prevalence and significance of PH in patients with Heart Failure (HF) with Reduced Ejection Fraction (HFrEF) as well as HF with Preserved Ejection Fraction (HFpEF), and those with valvular heart disease and provide insights into the complex pathophysiology of cardiopulmonary interrelationship in individuals with PH due to left heart disease. Furthermore, we provide a framework for diagnostic testing and an approach to optimal management of these complex patients based on current European Society of Cardiology (ESC) guidelines.
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PMID:Pulmonary Hypertension secondary to Left Heart Disease. 2890 48