Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For six months after bone marrow transplantation (BMT) there is a risk of 5 to 15% to suffer from interstitial pneumonia due to pneumocystis carinii (PcP). Prophylaxis with trimethoprim/sulfamethoxazol is therefore routinely and successfully applied. However myelotoxicity, allergic reactions, augmentation of the risk of nephrotoxicity with cyclosporine A and noncompliance may be serious problems. Since the prophylaxis of PcP with pentamidine-aerosol proved to be effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate the toxicity, safety, practicability and possible resorption of pentamidine when applied as aerosol. The first of 43 patients were treated with 60 mg pentamidine on two days before, at the day of BMT and 14 days after BMT. Starting four weeks after BMT, 300 mg pentamidine were given every four weeks up to six months. After the study, the four 60 mg inhalations were replaced by two 300 mg inhalations before BMT, because this proved to be more convenient for the patients. There was no pneumonia due to pneumocystis carinii. The only noteworthy side effects observed were cough (19.8%), salivation (9.6%) and sore throat (5.7%). In general pentamidine was well tolerated and well accepted by the patients. Pentamidine could only be detected in the serum of 40 to 60% of all patients. In those patients the serum levels were 7.5 to 9 ng/ml and similar to concentrations found in comparable patients with AIDS. We conclude, that pentamidine-aerosol has only minor side effects, is well tolerated and safe and is therefore an attractive alternative for PcP-prophylaxis after BMT.
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PMID:[Risk factors and prevention of pneumocystis carinii pneumonia after bone marrow transplantation]. 146 Dec 27

In patients, urinary levels of pentamidine have been shown to reflect pulmonary deposition of aerosolized drug. Using urinary levels and air filter samples, we assessed factors responsible for health care worker (HCW) exposure. We measured serial urine samples in HCWs who administered aerosol pentamidine over an 11-month period and compared them with serial urine levels measured over 30 days in a normal volunteer in whose lungs a known amount of pentamidine (3.39 mg) had been deposited. Ambient exposure to pentamidine was determined by continuous high volume air sampling in the treatment room during routine therapy. In addition, the amount of pentamidine released by six HIV-positive subjects, performing tidal breathing with a Respirgard II nebulizer in an airtight booth, was measured by extracting air from the booth through a filter. The effect of adding noseclips, of coughing (with nebulizer shut down), and of removing the nebulizer from the patient's mouth without turning it off, were determined. Pentamidine in the urine of the normal volunteer reached a peak concentration of 9.5 ng/mg creatinine/ml and was detectable for 30 days following the exposure. In HCWs, pentamidine was detected intermittently in four of five individuals with levels as high as 18.2 ng/mg creatinine/ml. Samples of ambient treatment room air indicated small daily releases of pentamidine (0.013 +/- 0.02 mg per patient treated), but simultaneous urine levels in HCWs were negative. The data from the airtight booth revealed that removing the nebulizer from a patient's mouth without turning it off caused a 360-fold increased in pentamidine release compared to tidal breathing. Coughing resulted in a 6.9 (range 0.9-14.2)-fold increase in release, while the addition of noseclips had no significant effect. The pattern of intermittently positive urine tests and the low levels of ambient pentamidine detected in the air of the treatment room suggest that HCWs are being exposed to episodic but high concentrations of pentamidine. High level exposure is most likely to occur during treatment interruptions which are usually precipitated by coughing episodes. Because of the intermittent pattern of exposure and slow clearance of pentamidine, urine assay is useful for detecting high intermittent exposure. Random air sampling is a sensitive indicator of low level exposures but may not detect episodic high level releases.
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PMID:Exposure of health care workers to aerosolized pentamidine. 844 22

The continuing growth of the acquired immunodeficiency syndrome (AIDS) epidemic has caused a parallel increase in patients with Pneumocystis carinii pneumonia (PCP). PCP has a wide spectrum of severity, from mild disease to severe parenchymal lung damage. Outcome is determined by severity of lung injury, the underlying physical condition of the patient, and concomitant infections. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine are effective therapeutic agents; however, both cause a high incidence of adverse reactions. TMP-SMX therapy can be made safer by careful monitoring and dose adjustment. Pentamidine toxicity, especially hypoglycemia, appears to be cumulative dose-dependent. Experimental therapies, including TMP-dapsone and aerosolized pentamidine, appear promising in mild to moderate disease, while trimetrexate may be more effective in severe disease. Corticosteroids are unproven in decreasing mortality. Prophylaxis of PCP is possible with TMP-SMX but the high rate of adverse reactions make long-term therapy difficult. Other oral therapies such as dapsone, pyrimethamine/sulfadoxine are also promising but not yet tested. Aerosolized pentamidine is effective and safe for prophylaxis regimen when administered correctly. Airway irritation as manifested by cough and/or wheezing is a common adverse effect of aerosolized pentamidine.
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PMID:Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: pathophysiology, therapy, and prevention. 266 34

Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients who were diagnosed by the aspiration-lung-biopsy. They were treated with 4 mg/kg of pentamidine isethionate intravenously administered followed by pentamidine aerosol inhalation. Although clinical and laboratory findings were improved by the fifth or seventh day of intravenous therapy, substantial leukocytopenia, from 3,000/cmm to 600/cmm and from 2,700/cmm to 1,000/cmm, occurred. At this point, the method of pentamidine administration was switched to inhalation. Pentamidine 600 mg in 30 ml distilled water was aerosolised using ultrasonic nebuliser and exposed for a 30-minute period once daily. In both cases, chest x-rays showed improvements: The disappearance of P. carinii were obtained in two weeks. Mild coughing was the sole adverse reaction encountered during the course of aerosol inhalation.
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PMID:Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients: supplemental treatment with aerosolised pentamidine isethionate. 278

A 44-year-old man with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who suffered adverse effects from treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was then treated with pentamidine isethionate is described, and approved and investigational drugs used in the management of PCP in the AIDS patient are discussed. After taking TMP-SMX, 240 mg trimethoprim and 1200 mg sulfamethoxazole, four times a day orally for 10 days at home, the patient was hospitalized complaining of nausea, vomiting, diarrhea, and fever. Intravenous TMP-SMX was begun at a dosage of 18 mg/kg/day of trimethoprim. Four days later, his condition had deteriorated and he had elevations of liver enzymes and a decrease in white blood cell (WBC) count. TMP-SMX was discontinued and pentamidine isethionate was started at a dosage of 4 mg/kg/day i.v. His symptoms and fever subsided and his liver enzyme levels and WBC count improved. After nine days of pentamidine his WBC count decreased; pentamidine was suspected as the cause and discontinued; no further therapy was needed. PCP was the initial infection that established this patient's diagnosis of AIDS. The patient did not have exertional dyspnea and nonproductive cough, which are usually seen in AIDS patients with PCP. TMP-SMX 20 mg/kg/day, based on the trimethoprim content, is the usual initial treatment for PCP. Adverse effects of TMP-SMX develop more frequently in AIDS patients than in non-AIDS patients with PCP. The recommended dose of pentamidine isethionate for the treatment of PCP is 4 mg/kg/day, im. or i.v. A few studies have shown good response to aerosolized pentamidine. Trials of investigational agents have excluded patients with severely compromised respiratory status; eflornithine, dapsone in combination with trimethoprim, and trimetrexate have been used. Corticosteroids should be considered a last effort until additional data are available. TMP-SMX may be used to prevent recurrence of PCP or to prevent the initial occurrence of PCP in AIDS patients. Intravenous or aerosol doses of pentamidine may be effective as prophylaxis. Sulfadoxine-pyrimethamine tried as prophylaxis produced adverse reactions. Despite its higher incidence of serious adverse effects in the AIDS population, TMP-SMX is considered preferable to pentamidine for initial therapy. Pentamidine is preferred for patients with documented allergy to TMP-SMX or failure to respond to a five- to seven-day course of TMP-SMX.
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PMID:Treatment of Pneumocystis carinii pneumonia in patients with AIDS. 313 63

1. Pentamidine is routinely used to reduce the incidence of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus, but it has been described as inducing pulmonary adverse effects, such as cough and bronchospasm. 2. In this paper we have investigated the effects of pentamidine on guinea-pig isolated main bronchi and human isolated bronchi. Pentamidine induced a concentration-dependent contraction in both preparations with pD2 values of 9.64 +/- 0.07 (n = 8) and 9.73 +/- 0.06 (n = 8) and a maximal effect (Emax) of 40 +/- 4% and 34 +/- 5% of the response to acetylcholine (1 mM) in guinea-pig and human bronchi respectively. Atropine (0.01 to 0.1 microM) and the muscarinic M3 receptor antagonist, hexahydro-siladiphenidol (0.1 and 1 microM) inhibited pentamidine-induced concentration-responses in both preparations in a non-competitive manner, whereas only high concentrations of the M1 receptor antagonist pirenzipine (1 microM) inhibited pentamidine concentration-response curves. 3. The cholinesterase inhibitor, tacrine (1 microM), potentiated the effect of pentamidine; in contrast, morphine inhibited pentamidine-induced responses. 4. The bronchoconstrictor effect of pentamidine on guinea-pig and human isolated bronchi was not modified by the H1 histamine receptor antagonist, mepyramine, by indomethacin or by the neurokinin NK1 and NK2 receptor antagonists, CP-96,345 and SR 48969 respectively, suggesting that neither histamine receptor stimulation, arachidonic acid derivative formation, nor tachykinin release are involved in pentamidine-induced contraction of human and guinea-pig airways. 5. Our overall results suggest that pentamidine induces contraction of guinea-pig and human isolated bronchi through prejunctional cholinergic nerve stimulation.
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PMID:Indirect muscarinic receptor activation by pentamidine on airway smooth muscle. 893 15