Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs used mainly for the treatment of hypertension, such as angiotensin I-converting enzyme (ACE) inhibitors, can cause pancytopenia. The underlying cause of this side effect remains unknown. In the present study, long-term bone marrow cultures (LTBMCs) were utilized to evaluate the role of captopril (D-3-mercapto-2-methylpropionyl-L-proline), one of the potent ACE inhibitors, in regulating hematopoietic stem/progenitor cell proliferation. Captopril (10(-6) M final concentration) was added to LTBMCs at the beginning of the culture period and at weekly intervals for six weeks. There was no toxicity to the bone marrow cells as measured by the unchanged cell number in the nonadherent layer during the whole culture period, and there was an increased cellularity of the adherent layer at the end of the six weeks of treatment. However, captopril decreased the proportion of granulocyte-macrophage colony-forming cells (GM-CFCs) in S phase at weeks 2 and 3 as well as that of high proliferative potential colony-forming cells (HPP-CFCs) at week 3 in the nonadherent layer. There was no change in the kinetics of the GM-CFCs and HPP-CFCs present in the adherent layer. These results suggest that captopril causes myelosuppression by inhibiting hematopoietic cell proliferation of progenitor and stem cells rather than depleting cells of the bone marrow microenvironment.
...
PMID:Captopril inhibits the proliferation of hematopoietic stem and progenitor cells in murine long-term bone marrow cultures. 1060 62

Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.
...
PMID:Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. 1160 67

Rapamycin/sirolimus (SR), trade named Rapammune (Wyeth-Ayerst, Sydney, Australia), is a potent immunosuppressive drug associated with myelosuppression, hypertension, hyperlipidemia, and infection. Rapamycin/sirolimus-induced pneumonitis has been described previously in renal transplant recipients, and this report describes a stable heart-lung transplant recipient who developed a pulmonary infiltrate that reversed after ceasing SR therapy. We believe that immunosuppression-induced pneumonitis in a lung allograft is a serious dilemma for lung transplant physicians
...
PMID:Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation. 1258 72

Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.
...
PMID:Safety and tolerability of linezolid. 1273 Jan 42

Dermatologists use a variety of systemic drugs, some of which can cause severe adverse reactions and even fatalities. Ivermectin, a well-tolerated drug, can cause severe neurological side effects, whereas metronidazole, in high cumulative doses, has been associated with convulsions and rarely with hepatotoxicity. Dapsone is associated with frequent hematologic side effects, such as methemoglobinemia, hemolysis, and anemia. Although hepatotoxicity is rare and usually mild and reversible with the new antifungal agents, severe cutaneous reactions (such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and anaphylaxis) have been reported. Even a relatively safe drug such as acyclovir has been reported to be the cause of renal failure and neurotoxicity. Retinoids can cause not so benign "benign" intracranial hypertension. Methotrexate can cause not only liver toxicity, but also myelosuppression and pancytopenia, which may be acute and life threatening. Nephrotoxicity is a well-recognized side effect of cyclosporine, whereas thrombotic thrombocytopenic purpura, which is associated with high morbidity and mortality, is less well known. Dermatologists should be familiar with these and other severe adverse reactions of the most popular and most used systemic medications of our trade.
...
PMID:The life-threatening complications of dermatologic therapies. 1580 12

Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylation in vitro and in vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.
...
PMID:Hydralazine target: from blood vessels to the epigenome. 1650

PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.
...
PMID:Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). 1945 27

VEGF and mTOR inhibitors have encouraging clinical activity for patients with advanced renal cell carcinoma (RCC), but may lead to significant short- and long-term toxicities. Although 40-70% of adverse events (AEs) are grade 1 and 2, 10-20% of patients develop grade 3 or 4 AEs requiring dose reductions, drug holidays or treatment discontinuation. The long-term impact of the most common grade 3 and 4 AEs observed in Phase III trials evaluating VEGF and mTOR inhibitors, including hypertension, decreased left ventricular ejection fraction, hand-foot-syndrome and myelosuppression, are a concern in RCC patients who are living longer and receiving chronic sequential or combination therapy. There is a clear need to develop a more rational way to individualize therapy for RCC. Long-term follow-up from existing Phase II/III trials should provide us with increased understanding of the potential implications of AEs in RCC patients. Prevention, early recognition and aggressive management of side effects are fundamental to avoid significant long-term complications and unnecessary dose reductions, which can ultimately reduce the efficacy of these novel agents.
...
PMID:Toxicity associated with the long-term use of targeted therapies in patients with advanced renal cell carcinoma. 1949 16

Long-term allograft survival poses a major problem in pediatric renal transplantation, with allograft nephropathy being the principal cause of graft failure after the first post-transplant year. The mechanisms of nephron loss resulting in graft dysfunction are multiple, comprising both immunologic factors such as acute and chronic antibody- or T-cell-mediated rejection and non-immunologic components. The latter include peri-transplant injuries and renovascular lesions (renal artery stenosis, thrombosis) as well as cardiovascular risk factors such as arterial hypertension and hyperlipidemia. Another relevant issue leading to progressive nephron loss and declining kidney transplant function is acute and chronic nephrotoxicity induced by the calcineurin inhibitors (CNIs) ciclosporin (cyclosporine microemulsion) and tacrolimus. Furthermore, the presence of an abnormal lower urinary tract as well as bacterial (recurrent pyelonephritis) and viral (cytomegalovirus [CMV], polyomavirus [BK virus; BKV]) infections are crucial factors involved in the incidence of chronic allograft dysfunction and graft failure. Renovascular lesions and lower urinary tract obstruction are typical indicators for surgical intervention. The aim of treatment in pediatric patients with renal failure secondary to a dysfunctional lower urinary tract is to create a sterile, continent, and nonrefluxive reservoir. Surgical techniques such as bladder augmentation and the introduction of intermittent catheterization and anticholinergic therapy have significantly improved graft outcome. Arterial hypertension, another factor responsible for graft function deterioration in pediatric renal transplant recipients, is controlled preferably by the use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists, which are known to possess nephroprotective properties in addition to their potent antihypertensive effects. Although treatment of subclinical rejection with augmented immunosuppression has been associated with better graft survival, an increase of the immunosuppressive level to avoid subclinical rejection should be weighed against the risk of infection. The majority of viral infections affecting kidney allografts are caused by CMV and BKV. Antiviral CMV prophylaxis or pre-emptive therapy with ganciclovir has been shown to have beneficial effects in the pediatric renal transplant population. Treatment of BKV-induced nephropathy is based on reduction of the immunosuppressant therapy, although specific antiviral agents such as cidofovir and leflunomide are known to inhibit BKV. However, cidofovir itself is nephrotoxic and should therefore be administered cautiously to pediatric renal transplant patients. Since CNIs are likewise known for their nephrotoxic effects, especially with long-term use, alteration of the immunosuppressant regimen is necessary in case of deteriorating graft function due to CNI-induced histopathologic changes. Complete CNI avoidance seems inappropriate because, in this situation in pediatric renal transplant recipients, other relatively potent immunosuppressant agents such as lymphocyte-depleting antibodies, which are frequently accompanied by a higher incidence of infections, are needed for rejection prophylaxis. CNI withdrawal and switching of the immunosuppressant regimen from CNI therapy to sirolimus may be an option for some pediatric renal transplant patients with less advanced graft function deterioration. Nevertheless, potential adverse events such as aggravation of proteinuria, hyperlipidemia, myelosuppression, and hypergonadotropic hypogonadism have to be considered, and controlled studies are lacking. At present, an immunosuppressant maintenance therapy composed of low-dose tacrolimus or ciclosporin (CNI minimization) and mycophenolate mofetil with low-dose corticosteroids appears to be the most promising strategy to adopt in pediatric renal transplant recipients at low or normal immunologic risk.
...
PMID:Treatment strategies to minimize or prevent chronic allograft dysfunction in pediatric renal transplant recipients: an overview. 1987 24

Drugs used for treating inflammatory bowel disease are known to have a number of gastrointestinal and liver adverse effects. 5-ASA products are relatively safe and have few adverse events. In contrast sulfasalazine has side effects in 11-40% of treated patients including fatigue, nausea, abdominal pain and diarrhoea. Glucocorticoids can induce or propagate peptic ulcers and upper GI bleeding especially in combination with NSAIDs. Thioguanins may have severe gastrointestinal side effects including gastrointestinal complaints (in up to 12%), hepatotoxicity (up to 4%) and pancreatitis (1%). Nodular regenerative hyperplasia (NRH) is an important potential side effect of thiopurine therapy especially in men with Crohn's disease after ileocecal resection. NRH may ultimately lead to portal hypertension. A major concern of methotrexate therapy in IBD besides myelosuppression and pulmonary fibrosis is hepatotoxicity. 5mg of folic acid substitution per week potentially decreases gastrointestinal side effects by 80% without interfering with the efficacy of methotrexate. Besides renal dysfunction, tremor, hirsutism, hypertension and gum hyperplasia cyclosporine is known to have a number of gastrointestinal side effects that occur with less frequency such as diarrhoea (up to 8%) nausea and vomiting (up to 10%) and hepatotoxicity in 1-4%. Rare gastrointestinal adverse events are gastritis and peptic ulcers. Paying attention to these potential deleterious side effects is mandatory for physicians treating IBD patients.
...
PMID:Gastrointestinal and liver adverse effects of drugs used for treating IBD. 2022 29


<< Previous 1 2 3 4 Next >>

---