Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a non-randomized study the efficacy of itraconazole in preventing fungal infections in neutropenic patients was investigated. Forty-seven patients with acute leukemia or advanced lymphoblastic lymphoma were enrolled. Ninety-two episodes of severe neutropenia after chemotherapy were observed. Mean duration of neutropenia was 24 days. Norfloxacin was administered as prophylaxis against gram-negative infections and itraconazole 200 mg b.i.d. as antifungal prophylaxis. Surveillance cultures of throat, urine, feces and vagina or prepuce were performed regularly. Four patients died, two patients due to heart failure, two patients due to staphylococcal pneumonia. Only in one case Candida albicans was cultured from bronchoalveolar lavage fluid. No systemic mycosis or Aspergillus fumigatus pneumonia was documented. In a similar group of patients treated in the preceding 18 months nystatin was used as antifungal prophylaxis. In this group of patients six cases of Aspergillus fumigatus pneumonia, two cases of Candida albicans fungemia and one case of Candida glabrata pneumonia occurred of which six patients died. Itraconazole seems to be effective in preventing fungal infections in neutropenic patients and is well tolerated.
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PMID:Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients. 166 Jan 8

Glycogen storage disease type II (GSD II), Pompe's disease, is caused by the deficiency of acid alpha-D-glucosidase (GAA) in lysosome and is the most common form of GSD in Taiwan. Most cases are the infantile form. The disease is relentless and most patients die of cardiac failure and respiratory tract infection in the first year of life. At present, no treatment has been proved effective for this fatal disease. The applicability of enzyme replacement therapy is under investigation. However, high price and transient efficiency are the major problems to be solved. Accordingly, gene therapy by viral method has been conducted. In this study we constructed a plasmid that contained 5'-shortened BglII-NotI fragment human GAA cDNA, downstream of CMV promoter and bovine growth hormone polyadenylation signal, as well as AAV ITR region. When fibroblasts obtained from GSD II patients were cultured and infected with rAAV-GAA, the GAA activity of the fibroblasts increased four- to five-fold. Using acid maltase deficient (AMD) Japanese quail as the animal model, rcAAV-GAA 0.1 ml per site (1 x 10(9)-10) particles), totally 10 different sites to make 1 ml (1 x 10(1)0-11) particles), was injected into unilateral deep pectoral muscle of AMD quails. Medium (hepes) was only injected in the same way into the contralateral deep pectoral muscle to serve as control. Four days after injection, PAS staining showed disappearance of the glycogenosomes with regeneration of myocytes surrounding the intramuscular injected area as compared with the contralateral muscle of the same birds. Using anti-GAA monoclonal antibody, GAA was demonstrated on the regenerated myocytes by immunohistochemical staining and absent on the contralateral muscle of the same birds. Nevertheless, T lymphocytes infiltration was noted in both the rcAAV-GAA and hepes (medium) injected muscles and more prominent in the rcAAV-GAA-injected site. Functional evaluation demonstrated that wing flapping movement improved with wide flapping in the rAAV-GAA injected side, but not in the counterpart. Unfortunately, these histochemical and functional improvements faded away in 14 days, probably due to destruction of rcAAV by cell-mediated immunity of infiltrated T cells. Taken together, the present study suggests that rAAV can enter either human or quail cells and express and effectively reduce the glycogen accumulation in the skeletal muscle of AMD quails. These preliminary results are similar to these of low-dose rGAA replacement therapy. The mechanisms underlying the induction of cell-mediated immunity are unknown. How to elevate the number of packaged AAV, enhance the infectivity of AAV and reduce cell-mediated immunity must be solved in the future.
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PMID:Adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of Japanese quail with acid maltase deficiency. 1197 31

Itraconazole is a broad-spectrum antifungal agent. It rarely leads to adverse the cardiovascular effects, especially heart failure. We present here a case of a 60-year-old female patient with itraconazole induced heart failure.
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PMID:Heart failure induced by itraconazole. 2413 Mar 92

Itraconazole is a triazole agent used in the treatment of fungal infections and in some metastatic cancers. Its use has been associated with cardiovascular adverse events and particularly heart failure with preserved ejection fraction. We report the case of a 68-year-old male patient with a well-controlled hypertension treated with irbesartan 150mg/day since 2007. He developed a pulmonary aspergillosis on post-tuberculosis cavitary lesions treated in July 2011 with itraconazole 200mg/day. Early 2012, his antihypertensive treatment had to be gradually increased to a quadritherapy and his blood pressure was at 157/78mmHg at home. Hypokalemia was observed on several occasions as well as edema of the lower limbs. Plasma renin and plasma and urine aldosterone concentrations on treatment not interfering with the renin angiotensin system were low, associated with normal serum and urine cortisol, ACTH, SDHA and DOC, BNP and creatinine concentrations. Plasma itraconazole values were much above the therapeutic range. Left ventricular ejection fraction was preserved. There were no adrenal or renal artery abnormalities at the CT scan. Three months after stopping itraconazole, hypokalemia and edema disappeared and blood pressure was normalized with less treatment. Plasma renin and aldosterone concentrations were normalized. He had a pulmonary lobectomy for his pulmonary aspergillosis. Itraconazole may induce a resistant hypertension with low renin. The mechanisms of this adverse effect of itraconazole remain unknown.
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PMID:[Itraconazole: a new drug-related cause of hypertension]. 2495 75

Itraconazole is a commonly used antifungal drug. In addition to commonly described adverse effects, there have been few reports of heart failure with its use. We present two cases that developed acute systolic heart failure with Itraconazole use. A man in his early 30s was admitted with worsening leg swelling and dyspnoea on exertion. He had been on Itraconazole for blastomyces skin ulcer. His ejection fraction (EF) was found to be 10%-15%. Another man in his 50s was admitted with similar symptoms; his EF was 40%-45%. He had been on Itraconazole for forearm cellulitis. No other aetiology was identified in both patients despite extensive work-up including cardiac catheterisation. Itraconazole was stopped in both the cases. Our first patient did not improve even months after cessation of therapy and was referred for heart transplant. Our second patient improved after a few weeks, and his ejection fraction had improved on repeat testing.
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PMID:Cardiotoxicity with Itraconazole. 2840 Mar 99

Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.
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PMID:Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. 2998 45

Itraconazole is well known for carrying a black-box warning for new or worsening congestive heart failure. Single cases of other cardiac- and fluid-related disturbances have been reported periodically since its issuance. We describe a large cohort of patients on itraconazole experiencing a breadth of cardiac- and fluid-related toxicities, ranging from new-onset hypertension to cardiac arrest. A retrospective, single-center, large case series at a large tertiary medical center was conducted. Patients with itraconazole and cardiac toxicity-including hypertension, cardiomyopathy, reduced ejection fraction, and edema-in medical record between January 1, 1999, and May 21, 2019, were identified and assigned a Naranjo score; 31 patients were included with a Naranjo score of 5 or higher. There were slightly more male subjects than female subjects, average age was 66, and all subjects were Caucasian. Median time until presentation of adverse effects was 4 weeks (range: 0.3 to 104 weeks). Most common symptom was edema (74% of patients), followed by heart failure without and with preserved ejection fraction (19.4% and 22.6% of patients, respectively). Worsening or new hypertension was also common (25.8% of patients). Rarer were pulmonary edema, pericardial effusion, and cardiac arrest that occurred in 1 patient. In most cases, clinicians stopped itraconazole (74%) or decreased itraconazole dose (19%), resulting in improvement or resolution of symptoms. In 4 cases, the adverse effect did not resolve. Itraconazole can cause a range of possible serious cardiac and fluid-associated adverse events. Dose decrease or cessation usually resulted in symptomatic improvement or reversal.
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PMID:The Many Faces of Itraconazole Cardiac Toxicity. 3308 7