Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentamidine isethionate is a trypanocidal drug used for the treatment of Pneumocystis carinii pneumonitis. Hematological complications have occasionally been reported and include anemia, leukopenia, and thrombocytopenia. We report here several qualitative abnormalities of in vitro platelet function and coagulation that have not been described previously. Platelets were exposed in vitro to concentrations of pentamidine isethionate ranging from 0.5 to 100 mug/ml of platelet-rich plasma. Clot retraction, platelet adhesiveness to glass beads, and platelet aggregation (adenosine 5'-diphosphate [ADP], thrombin, epinephrine, collagen, and ristocetin) were inhibited in a dose-dependent fashion. The addition of pentamidine isethionate after aggregation had been initiated with ADP reversed both primary and, to a lesser degree, secondary aggregation. Platelet factor 3 availability and serotonin uptake and release (using collagen as the releasing agent) were not inhibited. Serotonin release with 10(-4) M ADP was slightly inhibited. Pentamidine isethionate prolonged the thrombin time of plasma at concentrations of 5 mug/ml and greater. The prothrombin time was prolonged at concentrations greater than 10 mug/ml of plasma. The inhibition of aggregation was reversed by washing and resuspension in plasma or by the addition of calcium or magnesium ions.
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PMID:In vitro inhibition of platelet function and coagulation by pentamidine isethionate. 92 Dec 38

Pentamidine isethionate, an antiprotozoal agent with therapeutic value against Pneumocystis carinii pneumonia, has been used for over 30 years without a precise understanding of its mechanism of pharmacologic action. We have previously reported that pentamidine has the capacity to inhibit the release of cytokines from macrophages through a post-translational processing event. The present studies were undertaken to assess the ability of pentamidine to modulate the detrimental effects of murine endotoxemia, a disease with a pathophysiology clearly linked to host-produced cytokines. Under conditions where normal B6C3F1 mice succumbed to the lethal effects of endotoxin, mice pretreated with pentamidine were significantly protected from both mortality and loss of thermoregulatory control. The EC50 for protection from mortality by pentamidine was approximately 11.4 mg/kg. These observations correlated with decreased serum levels of tumor necrosis factor (TNF) and interleukin 6. Inhibition of cytokines was not manifested as part of a generalized inhibition of protein synthesis as demonstrated by the lack of significant modulation of serum albumin in pentamidine-treated animals. In addition to decreased serum concentrations of cytokines, lungs isolated from mice treated with both pentamidine and endotoxin exhibited a decreased release of TNF compared to lungs isolated from mice treated with vehicle and endotoxin. The lower levels of TNF released from lung tissue in pentamidine-treated mice correlated with a lesser degree of alveolar deterioration than was observed in vehicle-treated mice. These data indicate that following endotoxin administration, pentamidine has a protective and antiinflammatory role both systemically and in the lung and suggest that inhibition of inflammatory cytokines may be one mechanism operable in the therapeutic activity of the drug against P carinii pneumonia.
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PMID:Pentamidine blocks the pathophysiologic effects of endotoxemia through inhibition of cytokine release. 153 59

Pneumocystis carinii pneumonia is the most common life-threatening disease diagnosed in patients infected with the human immunodeficiency virus (HIV). Patients treated for their initial episode are at risk for recurrence of the disease. HIV-positive patients with low T4 lymphocyte counts are also at risk. Conventional treatment regimens with parenteral pentamidine isethionate (Pentam 300) or trimethoprim-sulfamethoxazole have a 50% to 60% incidence of serious adverse effects and a 20% to 40% rate of failure. Aerosolized pentamidine represents a promising new therapy for HIV-infected patients. Major adverse reactions have not been reported with its use. The Food and Drug Administration's (FDA's) recent approval of aerosolized pentamidine may also have a positive effect on healthcare costs by preventing episodes of P carinii pneumonia. In addition, FDA approval may result in reimbursement of patients for this new therapy by more insurance companies.
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PMID:Aerosolized pentamidine in HIV. Promising new treatment for Pneumocystis carinii pneumonia. 266 72

The chemistry, spectrum of activity, mechanism of action, pharmacokinetics, adverse effects, and dosage and administration of pentamidine are reviewed, and the role of the drug in treating Pneumocystis carinii infections in immunocompromised patients is discussed. Pentamidine isethionate, an aromatic diamidine compound, is active against certain protozoan organisms. Used extensively in the tropics in the treatment of Trypanosoma and Leishmania infections, its value in the management of Pneumocystis carinii infections has been demonstrated in infected immunosuppressed children and adults. Recently, interest in pentamidine has increased with the rising number of patients with acquired immunodeficiency syndrome (AIDS) who have P. carinii pneumonia. Pentamidine's mechanism of action and pharmacokinetic profile are not completely understood. Pentamidine is distributed extensively after i.v. or i.m. administration, with a volume of distribution of 3 L/kg. Appreciable quantities of pentamidine concentrate in the urine, and drug levels are detectable for up to six to eight weeks after cessation of therapy. After aerosol administration, the drug is almost exclusively recovered from the lung, with little extrapulmonary distribution. Available data suggest that approximately 50% of patients who receive the drug by the i.v. or i.m. route will experience some drug toxicity (local pain, sterile abscesses at the intramuscular injection site, hypoglycemia, hypotension, or azotemia), while adverse effects after aerosol therapy include bronchial irritation but little systemic toxicity. Regardless of the route of administration, pentamidine has emerged as a mainstay of therapy in the management of P. carinii pneumonitis in AIDS patients, especially in those who are allergic to the sulfa component of trimethoprim-sulfamethoxazole.
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PMID:Update on pentamidine for the treatment of Pneumocystis carinii pneumonia. 304 30

Pentamidine isethionate, an aromatic diamidine, is an antiprotozoal agent proven to decrease mortality from Pneumocystis carinii pneumonia in debilitated infants and immunodeficient adults and children. Like the combination antimicrobial agent co-trimoxazole, pentamidine has been shown in retrospective studies to resolve episodes of pneumonia in approximately 41 to 87% of patients, including those with the acquired immunodeficiency syndrome (AIDS), when used alone or as sequential therapy. Although about 45% of all patients given pentamidine experience side effects--which may include nephrotoxicity, hypotension, hypoglycaemia or local reactions--in patients with AIDS the incidence of side effects is less with pentamidine than with co-trimoxazole. Thus, despite its profile of potentially severe side effects, pentamidine isethionate is a proven antimicrobial agent with a distinct place in the treatment of Pneumocystis carinii pneumonia in the growing population of AIDS patients.
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PMID:Pentamidine isethionate. A review of its antiprotozoal activity, pharmacokinetic properties and therapeutic use in Pneumocystis carinii pneumonia. 355 96

Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.
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PMID:Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases. 390 52

Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.
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PMID:Treatment of Pneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer: report from the Children's Cancer Study Group. 638 15

We reviewed the charts of 52 patients infected with human immunodeficiency virus (HIV) who received at least three consecutive doses of intravenous pentamidine as prophylaxis for Pneumocystis carinii infections. Pentamidine isethionate was administered intravenously over 60-90 minutes once a month, at a dosage of 4 mg/kg, in 250 mL of 5% dextrose in water. During 387 months of administration of primary prophylaxis to 37 patients, no cases of P. carinii pneumonia were observed. During 200 months of administration of secondary prophylaxis to 15 patients, only one case of P. carinii pneumonia was diagnosed (6.0 cases per 100 patient-years). Side effects associated with the intravenous pentamidine were mild and did not necessitate withdrawal of the drug. Once-a-month administration of intravenous pentamidine is a valid alternative as prophylaxis for P. carinii pneumonia for patients who are intolerant of sulfonamides.
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PMID:Once-a-month administration of intravenous pentamidine to patients infected with human immunodeficiency virus as prophylaxis for Pneumocystis carinii pneumonia. 808 50