Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spurious polycythemia is not a primary disease process. It sometimes may be nothing more than an unusual, but normal, physiologic state. In other instances, however, it is associated with a true abnormality of plasma volume. Although there is probably overlap between these extremes, differentiation of these subclasses may be of prognostic significance. The elevation in hematocrit bears no relation to morbidity, and, because there is no evidence of abnormal erythroid proliferation, reduction of red cell volume via phlebotomy or myelosuppression is inappropriate. Nonhematologic parameters, particularly hypertension, are the major factors of significance in the substantial cardiovascular morbidity in spurious polycythemia, and they demand attentive and aggressive management.
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PMID:Spurious polycythemia. 119 27

In a high-dose schedule for disseminated neuroblastoma, eight courses of chemotherapy were administered every 10 days, regardless of myelosuppression, to eradicate tumour cells rapidly and reduce emergence of drug-resistant clones. Relatively non-myelotoxic vincristine and cisplatin were alternated with high-dose cisplatin-etoposide and cyclophosphamide-etoposide. Of 12 evaluable patients, there were 1 complete (CR), 3 very good partial (VGPR), 5 partial (PR) and 3 mixed responses (MR) 100 days after starting treatment. 6 out of 9 achieved a bone marrow CR at 40 days. 9 of 11 primary tumours were completely resected, after which 4 patients had CR, 3 VGPR (bone scan alone being abnormal), 4 PR and 1 mixed response (MR). Myelotoxicity was the major adverse effect. The only death was due to fungal infection. Clinically important renal dysfunction occurred in 3 patients. 4 had convulsions and 4 temporary hypertension. This schedule produced a rapid response and its toxicity, though serious, was manageable. Further evaluation is warranted.
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PMID:High-dose rapid schedule chemotherapy for disseminated neuroblastoma. 138 81

Cyclosporin is a potent, widely used specific immunosuppressive agent which affects T-helper cells, and has little myelotoxicity. Its pharmacokinetics are complex and many of its actions remain poorly understood. Numerous side effects have been reported, affecting most organs. Most troublesome have been renal injury, systemic hypertension and vascular changes. Oral use is more effective than intramuscular and safer than the intravenous route. Interactions with other drugs include those which affect hepatic metabolism and those which reduce clearance. Aminoglycosides, macrolide antibiotics, imidazole derivatives, calcium channel blockers, sulphonamides and steroids are included in such interactions. Other metabolic effects of cyclosporin are more subtle and include hyperchloraemic alkalosis, changes in serum potassium and magnesium and effects on testosterone and prolactin levels. Acute poisoning with cyclosporin has been reported, again without myelosuppression. Cyclosporin is an important agent with multisystem toxicity, which requires precise monitoring of drug concentrations, liver and renal function, haemoglobin levels and plasma electrolytes. Cyclosporin pharmacodynamics and interactions with other drugs need to be carefully considered if lower rates of toxicity are to be achieved.
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PMID:Adverse reactions and interactions of cyclosporin. 328 88

Two cases of infants with congenital leukemia who had severe, refractory hypertensive reactions to teniposide (VM-26) are described. Patients on a 5 mg/kg twice weekly schedule of teniposide had hypertensive reactions in which their systolic blood pressure was greater than 200 mm Hg after the second dose of teniposide. Hypertension combined with myelosuppression resulted in the patient's death in one case. Although the exact mechanism of this unusual toxicity of teniposide remains unknown, it might be an age-specific problem, considering the very young age of our patients. Meticulous monitoring of vital signs, including blood pressure, is mandatory in leukemic infants receiving teniposide.
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PMID:Severe hypertensive reactions to teniposide (VM-26) in infants with congenital leukemia. 347 27

Seven patients with refractory multiple myeloma (readily evaluable for response) were treated in a Phase II trial with poly(I,C)-LC using a 3 times per week intravenous schedule. Serial immunologic testing included assessment of natural killer (NK) cell activity, antibody-dependent cytotoxicity, delayed hypersensitivity, and in vitro mitogen responses. One patient had a partial response (PR) of 6-month duration, and 3 other patients had objective responses (less than PR). Significant interferon induction occurred, but levels dropped substantially with serial dosing. Major toxicity included hypertension, hypotension, fever, and myelosuppression. The demonstration of modulation of myeloma progression in this refractory population was encouraging.
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PMID:Poly(I,C)-LC as an interferon inducer in refractory multiple myeloma. 393 57

A study was carried out to establish the maximum tolerated dose of human lymphoblastoid interferon and to define its side effects when given by intramuscular injection. Pyrexia limited the initial dose to a maximum of 3 megaunits/m2 body surface area, but tolerance to this effect developed over 4 to 5 days and the dose was then increased to 5 to 7.5 megaunits/m2; subjective disturbance prevented further increase in dose, but 2.5 to 5.0 megaunits/m2 daily was well tolerated and appears suitable for long-term administration. Other side effects were hypertension, hypotension, myelosuppression, and disturbance of liver-function tests. All toxic effects were reversible on stopping the interferon. Two patients showed evidence of tumour regression, indicating that further trials are justified to define the extent of anticancer activity.
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PMID:Initial evaluation of human lymphoblastoid interferon in patients with advanced malignant disease. 615 64

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Advances in immunosuppressive therapy have resulted in significantly improved patient and graft survival after solid organ transplantation. However, increased use has brought attention to specific toxicities associated with the use of these agents. Corticosteroid therapy can result in a wide array of short and long term toxicities. Management of these effects has focused on alternate day and dosage reduction protocols. Myelosuppression, hepatotoxicity, alopecia and gastrointestinal adverse effects are associated with azathioprine and generally respond to a reduction in dosage or withdrawal. Cyclophosphamide myelosuppression is managed in a similar manner. Use of cyclosporin, while the mainstay of immunosuppressive therapy, is often complicated by several well documented adverse effects. Short and long term nephrotoxicity is often managed through pharmacokinetic dosing strategies as well as pharmacological intervention with calcium channel blockers, prostaglandin analogues, pentoxifylline and thromboxane antagonists. Cyclosporin-induced hypertension, hyperlipidaemia, hyperkalaemia and hyperuricaemia are generally responsive to appropriate dietary restrictions and pharmacological therapies. The adverse effects associated with polyclonal antilymphocyte agents (fever, chills, rash, arthralgias) occur in response to the administration of foreign protein substances but can be prevented by pretreatment with corticosteroids, diphenhydramine and paracetamol (acetaminophen). The administration of muromonab CD3 (OKT3) stimulates the release of cytokines resulting in potentially severe complications seen during the first 1 or 2 doses. Pretreatment with diphenhydramine, low dose corticosteroids and paracetamol as well as proper fluid management has reduced the incidence of this syndrome. However, agents such as high dose corticosteroids, indomethacin, pentoxifylline and anti-tumour necrosis factor monoclonal antibodies may further decrease the severity of cytokine-induced toxicity. Antimurine antibodies may also develop during muromonab CD3 therapy, potentially limiting the efficacy of this agent. However, continued concomitant immunosuppressive therapy has significantly reduced antibody formation. In summary, as newer agents are developed with narrow therapeutic windows, it will be critical to identify specific drug toxicity and to develop preventative and management therapeutic strategies.
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PMID:Prevention and management of the adverse effects associated with immunosuppressive therapy. 839 89

Antineoplastons, which were firstly described by Burzynski, are naturally occurring peptides and amino acid derivatives which control neoplastic growth. We conducted a toxicological study of the Antineoplastons A-10 and AS2-1 in combination with other anticancer agents or radiation in 42 patients, 46 tumors with terminal stage cancer. Antineoplaston A-10 oral formulation and A-10 injectable formulation was administered in 14 and 25 patients respectively. The maximum daily dose was 10 g and 40 g, respectively and the longest term of administration was 610 days and 67 days, respectively. Antineoplaston AS2-1 oral formulation and AS2-1 injectable formulation was administered in 33 and 10 patients, respectively, the maximum daily dose was 12 g and 30 g, respectively, and the longest term was 1070 days and 25 days, respectively. The major adverse effects that may have been related to these agents as used in combination with other conventional chemotherapeutic agents or radiation were general weakness, myelosuppression, and liver dysfunction, but these effects were not seen when either Antineoplaston was administered alone. The minor adverse effects observed in single use of either Antineoplaston A-10 or AS2-1 were excess gas, maculopapullar rash, fingers rigidity, reduced cholesterol, reduced albumin, increased amylase, eosinophilia, increased alkaline phosphatase, headache, hypertension, palpitation, peripheral edema but these adverse effects did not limit to continuation of either agent. The evaluation of the usefulness of the Antineoplastons in combination therapy based on the imaging findings during the course of treatment revealed disappearance or measurable shrinkage of the tumor lasting more than one months as visualized by magnetic resonance imaging or computed tomography was seen in 15 tumors (32.6%). No increase in size of tumor for more than 3 months was observed in 8 (17.4%). The mean survival time of these patients was significantly longer than that in patients with tumors showing progressive increasing (17.52 + 3.31 months vs 4.80 + 0.65 months, p < 0.005). Antineoplaston A-10 and AS2-1 are less toxic than conventional chemotherapeutics and they were useful in maintenance therapy for cancer patients.
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PMID:Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. 866 95

Twenty-three patients with advanced or recurrent endometrial carcinoma entered a prospective study of chemotherapy which consisted of carboplatin (300 mg/m2), methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3-weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg daily, p. o., until progression (JMF-M regimen). None had received prior chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had received radiotherapy. Response to treatment was evaluated every two courses. Objective response was seen in 17 of the 23 patients (74%, 95% confidence interval = 52-90%), with 2 long-lasting complete responses (9%). The median response duration was 10+ months (3-45+). The median survival was 16+ months (2-45+). The 2 complete responders, the first in the lung and the second in groin nodes, are without evidence or recurrence after 32 and 45 months, respectively. The regimen was given on an outpatient basis and was well tolerated. The major toxic effects were myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation treatment with MPA was discontinued because of thromboplebitis. In conclusion, the JMF-M regimen is highly active with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.
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PMID:Carboplatin, methotrexate and 5-fluorouracil in combination with medroxyprogesterone acetate (JMF-M) in the treatment of advanced or recurrent endometrial carcinoma: A Hellenic cooperative oncology group study. 1020 74


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