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PubMedDate not supplied

Preliminary data on the action of nesosteine, a mucomodifying drug, on mucociliary transport.

Nesosteine, which is active on airway secretions, has been studied by assessment of the mucociliary clearance of the frog palate. Sputum was collected from patients admitted to hospital with acute exacerbations of chronic bronchitis with mucous expectoration. The relative speed of transport was measured for each patient before and after oral administration of 600 mg/day nesosteine. A significant increase in the mucus transport rate was found at the end of treatment.

Aged↗
PubMedDate not supplied

The management of cystic fibrosis with carbocysteine lysine salt: single-blind comparative study with ambroxol hydrochloride.

The effectiveness of carbocysteine lysine salt monohydrate (SCMC-Lys) and ambroxol hydrochloride (ABX) in the management of respiratory impairment was compared in a single-blind, randomized study of 26 cystic fibrosis patients with similar baseline characteristics. Adults received either SCMC-Lys 900 mg or ABX 33 mg three times a day and children under 14 years of age either SCMC-Lys 270 mg three times a day or ABX 10 mg four times a day. All treatments were given orally for 80 days and at the end of this control period both groups showed significant improvement in chest sound score but improvement in cough score was observed only in those receiving SCMC-Lys. Expectorate viscosity and elasticity decreased significantly in both groups. In SCMC-Lys-treated patients paCO2 decreased and paO2 and Hb O2 saturation increased while only paO2 increased significantly in those treated with ABX. An increase in tidal volume, peak expiratory flow values and forced expiratory volume were evident in those receiving SCMC-Lys while significant increases in forced expiratory flow were recorded in those receiving ABX. SCMC-Lys patient's Shwachmann index improved significantly and conversely to the ABX patients. No adverse events were recorded in either treatment group. The study concluded that SCMC-Lys is at least as effective as ABX in improving respiratory function in patients with cystic fibrosis.

Adolescent↗
PubMed2001

Nebulized heparin in Burkholderia cepacia colonized adult cystic fibrosis patients.

Viscous negatively charged cystic fibrosis (CF) sputum allows colonization by pathogens, inducing a chronic inflammatory response. Heparin thins sputum by decreasing the mucin molecule amino group negative charge, altering its intermolecular hydrogen bonding, and ionically shielding its polyionic moieties. It also has an anti-inflammatory effect within the lung. It may, therefore, be useful in the treatment of CF patients. In order to test this, six fully informed Burkholderia cepacia colonized stable adult CF patients, received 25,000 IU nebulized heparin sulphate daily for 7 days. Subjective sputum parameters, spirometry, platelets, coagulation parameters, and serum and sputum interleukin (IL)-6 and -8 were measured before and after treatment. All patients tolerated the heparin with no evidence of bleeding, thrombocytopenia or change in coagulation parameters. There was no change in spirometry, but a reduction in interleukins (sputum IL-6, p=0.01; sputum IL-8, p=0.002; serum IL-6, p=0.02; serum IL-8, p=0.02). Sputum was easier to expectorate (p < 0.04), with a trend towards thinner sputum (p=0.07) but no change in sputum volume. Heparin therapy was well tolerated and had an anti-inflammatory effect, with subjective sputum mucolysis. Further studies are necessary to define the role of heparin in the treatment of cystic fibrosis patients.

Adult↗
PubMed1997

Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline.

Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of cellular and fluid-phase markers of airway inflammation. We investigated the extent to which DTT treatment influences these measurements as compared with phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from 20 asthmatic subjects, was examined within 2 h. All portions which looked more solid (less fluid) than saliva were collected from the expectorate. The selected sputum was then divided into two portions: one treated with one volume of DTT and one volume of PBS, the other with two volumes of PBS. The filtrates were assessed blind for total and differential cell count, viability, and fluid-phase eosinophil cationic protein (ECP), fibrinogen, interleukin (IL)-5 and IL-8. Sputum treated with DTT compared with PBS had lower proportions of viable cells (median 66 versus 74%; p=0.003). In contrast, DTT-treated sputum had higher total cell counts (median 8.8 vs 2.8 x 10(6) mL(-1); p<0.001) and levels of ECP (median 1340 vs 584 mg x L(-1); p<0.001) The measurements were similar with respect to the proportion of eosinophils, neutrophils, lymphocytes, macrophages, and fluid-phase fibrinogen, IL-5 and IL-8. We conclude that dithiothreitol disperses cells more effectively and that this might account for the higher levels of eosinophil cationic protein. Dithiothreitol may affect cell viability, but the changes are not relevant with respect to cell counts. Additionally, dithiothreitol does not seem to influence the other measurements performed.

Adolescent↗
PubMed1978

Clinical therapeutic evaluation of methylcysteine hydrochloride in patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control.

A double-blind, between-patient, placebo controlled trial was carried out to investigate the effects of methylcysteine hydrochloride in patients with chronic obstructive bronchitis. After a 2-week washout period on placebo, 30 patients were allocated at random to treatment for 6 weeks with either methylcysteine (1200 mg daily in Week 1, 800 mg daily in Week 2, then 600 mg daily) or with identical placebo tablets on the same regimen. During the post-treatment period, all patients returned to a single-blind placebo regimen (6 tablets daily) for a further 14 days. Assessments were made at the start, at regular intervals during the trial, and at the end of the post-treatment period, of subjective and objective measures of clinical response, and measurements of pulmonary function and certain physico-chemical properties of sputum. The results showed that methylcysteine increased sputum volume, reduced the viscidity of sputum, and significantly improved the subjective assessments of ease of expectoration and severity and frequency of cough, leading to a definite improvement in the patients' clinical state. No side-effects of clinical significance were reported and no abnormalities were found in any of the haematological, hepatic and renal function tests carried out.

Adult↗
PubMed1992

[Effects of ambroxol HCl on the guinea pig tracheal mucous secretion and the rat pulmonary surfactant secretion].

The effects of orally administered ambroxol HCl (ambroxol) on guinea pig tracheal mucous secretion and rat pulmonary surfactant secretion were investigated histologically and biochemically. Ambroxol significantly increased the number of active goblet cells in guinea pig tracheal epithelium and total mucopolysaccharide level. Moreover, ambroxol significantly increased the neutral mucopolysaccharide level and PAS-positive substance in the guinea pig tracheal submucosal glands. Ambroxol did not show a significant effect on the content of the total phosphatidylcholine in rat lung lavage fluid, while ambroxol significantly increased the ratio of disaturated phosphatidylcholine to total phosphatidylcholine. From these results, it is suggested that ambroxol increases both the tracheal mucous secretion, especially the neutral mucopolysaccharide, and pulmonary surfactant secretion and these effects reflect part of the expectorant mechanism of the drug.

Ambroxol↗
PubMed1989

[Effects of inhaled bromhexine on the bronchomotor tone in rats and guinea pigs].

Bromhexine has been widely used as a mucolytic expectorant. Clinically, bromhexine is sometimes administered by inhalation. However, the effect of bromhexine by inhalation on bronchial musculature has not been documented. In the present study, the effect of inhaled bromhexine on bronchomotor tone in rats and guinea pigs was investigated. The bronchomotor tone was measured by a modified Konzett-Rössler method, and ventilation overflow (VO) was continuously recorded as an index of airway resistance. In rats, inhalation of bromhexine (0.1% and 0.2%, pH 5.3) caused no change in VO. At 0.2%, bromhexine slightly decreased systemic blood pressure (BP). In guinea pigs, bromhexine had no significant effect on VO at 0.2%, and it produced a significant but very slight increase at 0.1%. BP was slightly decreased by inhalation of bromhexine (0.1% and 0.2%, pH 5.3). N-Acetyl-L-cysteine, a cysteine-mucolytic (20%, pH 6.8), had no effect on VO and BP in either species. Inhalation of 0.1% bromhexine solution at pH 2.5, which was dissolved in tartaric acid solution, significantly increased VO, because of its acidity. From the above results, it is suggested that when the pH of the solution is considered, bromhexine has no or almost negligible effect on airway smooth muscles, and it may be useful as an effective mucolytic.

Administration, Inhalation↗
PubMed2003

Effect of guaifenesin on cough reflex sensitivity.

BACKGROUND: Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. STUDY OBJECTIVES: To evaluate the effect of guaifenesin on cough reflex sensitivity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Academic medical center. PARTICIPANTS: Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. INTERVENTIONS: On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. MEASUREMENTS AND RESULTS: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. CONCLUSIONS: Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Adult↗
PubMed1996

Erdosteine.

Erdosteine is a thiol derivative developed for the treatment of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis. Erdosteine contains 2 blocked sulfhydryl groups which are released following first-pass metabolism. The 3 active metabolites exhibit mucolytic and free radical scavenging activity. Erdosteine modulates mucus production and viscosity and increases mucociliary transport, thereby improving expectoration. It also exhibits inhibitory activity against the effects of free radicals produced by cigarette smoke. Clinical studies in patients with chronic obstructive lung disease have demonstrated the efficacy and tolerability of erdosteine. Erdosteine 300mg twice daily reduced cough (both frequency and severity) and sputum viscosity more quickly and more effectively than placebo and reduced the adhesivity of sputum more effectively than ambroxol 30mg twice daily. Co-administration of erdosteine and amoxicillin in patients with acute infective exacerbation of chronic bronchitis resulted in higher concentrations of the antibiotic in the sputum, leading to earlier and more pronounced amelioration of clinical symptoms compared with placebo. Erdosteine is associated with a low incidence of adverse events, most of which are gastrointestinal and generally mild.

Animals↗
PubMedDate not supplied

[Rheology of bronchial secretions and mucociliary transport (author's transl)].

Optimal relationships between mucociliary clearance and rheological properties of bronchial secretions expectorated by patients with chronic bronchitis have been analysed by successive measurements of visco-elasticity with a rotational rheometer and of transport velocity on frog palate mucosa. It appears that the role of the elastic component is predominent. Sputum characterized by very low strain recovery (SR less than 4 units) or conversely by very high elasticity (SR greater than 20 units) is transported at a low rate in comparison to that of the control frog mucus (relative transport rate less than 0.5). Pronounced hyperviscosity of sputum (no greater than 200 poises) appears also as a limiting factor to the mucociliary transport. The best transported secretions (relative transport rate greater than 0.7) are characterized by a relative elasticity (SR) of 4 to 13 units and a viscosity (no) of 25 to 200 poises. Under the action of mucolytic agents such as N-acetylcysteine, sputum initially characterized by low strain recovery (SR less than 4 units) is transported at a much slower rate which is related to the increased loss of elasticity. These results indicate that mucolytic drugs must be administered with great care in patients with chronic bronchitis. Moreover, they should not be used in patients with very low visco-elastic secretions which reflect the non-functional state of the bronchial mucosa.

Acetylcysteine↗
PubMed2000

Evaluating the efficacy of mucoactive aerosol therapy.

The aerosol route is attractive for the delivery of mucoactive medications. Mucoactive medications include mucolytics, which depolymerize polymers of mucin (classic mucolytics) or DNA/actin (peptide mucolytics), mucokinetic agents, which increase cough clearance, mucoregulatory medications, which decrease abnormal mucus secretion, and expectorants and ion channel modifiers. Despite the widespread use of these medications, there are few well conducted studies and thus few data clearly supporting (or failing to support) their use. This will change as our understanding of mucociliary physiology and pharmacology increases and as well designed and well powered clinical trials are conducted with appropriate outcome measurements. Effective mucoactive therapy should make a profound impact on the care of patients with chronic bronchitis, asthma, cystic fibrosis, and inflammatory airways disease, and will be essential for the effective delivery of gene therapy vectors and bioactive peptides to the airway epithelium.

Administration, Inhalation↗
PubMed2003

Diethylene glycol poisoning in Gurgaon, India, 1998.

OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2 months to 6 years who were admitted to two hospitals in Delhi between 1 April and 9 June 1998. METHODS: Data were collected from hospital records, parents and doctors of the patients, and district health officials. Further information was obtained from house visits and community surveys; blood and stool samples were collected from other ill children, healthy family members and community contacts. Samples of drinking-water and water from a tube-well were tested for coliform organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute renal failure developed after an episode of acute febrile illness with or without watery diarrhoea or mild respiratory symptoms for which the children had been treated with unknown medicines by private medical practitioners. On admission to hospital the children were not dehydrated. Median blood urea concentration was 150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6 mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty-three children were known to have died despite being treated with peritoneal dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a company in Gurgaon was found to be contaminated with diethylene glycol (17.5% v/v), but a sample of acetaminophen manufactured by the same company tested negative for contamination when gas-liquid chromatography was used. Thus, poisoning with diethylene glycol seems to be the cause of acute renal failure in these children.

Acute Kidney Injury↗
PubMed1998

[Comparison of pharmacological effects between cultispecies Sichuan Fritillary bulb (F. wabueasis, F. mellea) and wild Sichuan Fritillary bulb (F. unibracteata)].

The ethanol extracts from the cultured Sichuan Fritillary bulb have been proved similar to those from the wild one in treating coughing in mice, expectoration in rats, asthma in guinea pigs, bronchodilation of isolated lungs in mice, and cyclic nucleotide(cAMP, cGMP) in the plasma and lungs of mice. The acute toxicity of the cultured and wild species is also similar to each other. However, in terms of asthma relieving and cAMP level increment in the lungs, the cultured species F. wabueasis is significantly superior to the wild species of Fritillary bulb.

Animals↗
PubMed1998

[Determination of morphine in compound liquorice tablets by high performance liquid chromatography with SEP-PAK C18 cartridge pretreatment].

An efficient method combining SEP-PAK C18 cartridge solid phase extraction (SPE) with reversed-phase high performance liquid chromatography for the quantitation of morphine in the Compound Liquorice Tablet is presented. The tablets have been used for making expectoration easy and relieving cough for years. The tablet powder (approximately 1 tablet) was added into a stoppered centrifuge tube, and vertically extracted with 5 mL of 0.5% HAc for 5 min. After centrifugation the supernatant was transferred to a beaker and the extraction was repeated twice with 4 mL and then 3 mL of 0.5% HAc. Five millilitres of carbonate buffer (pH 8.9) was added to the combined extracts. A SEP-PAK C18 cartridge was pretreated by passing methanol and distilled water, using a glass syringe. The mixture was applied on it and allowed to flow through. The cartridge was washed first with 5 mL of 10% methanol solution and then the morphine was eluted with 4 mL of 70% methanol solution into a 5 mL volumetric flask and was finally diluted to volume with 70% methanol solution. Analysis was performed on a mu-Bondapak C18 column(300 mm x 4.6 mm i.d., 10 microns) with 0.1 mol/L NaH2PO4-methanol(5:1) as the mobile phase and detection at 286 nm. The average recovery of morphine was (101.2 +/- 1.5)% and RSD was 1.5%. The method is simple, rapid, accurate, and reproducible, and can be used in drug control.

Antitussive Agents↗
PubMed2001

Oral neltenexine in patients with obstructive airways diseases: an open, randomised, controlled comparison versus sobrerol.

BACKGROUND: The synthetic mucolytic neltene-xine is an amide derivative of ambroxol and thiophencarboxylic acid. The aim of this open, randomised, controlled study versus sobrerol was to evaluate the efficacy and tolerability of neltenexine (oral granules in sachets) as compared with sobrerol (oral granules in sachets), administered to patients with obstructive airways disease. METHODS: Thirty male and female patients were recruited. The exclusion criteria were allergy to neltenexine or sobrerol, an assessed diagnosis of severe bronchospasm requiring beta2-agonists, corticosteroids or aminophylline, pregnant or nursing women, cystic fibrosis, active tuberculosis or an assessed diagnosis of bronchiectasis. No infections of other organs (such as urinary tract infections) were present at baseline. Concomitant treatment with antitussives or other mucolytic agents was not allowed during the course of the study. Fifteen patients were randomised to treatment with neltenexine, 1 sachet thrice daily for 20 days orally (neltenexine group) and 15 patients to treatment with sobrerol, 1 sachet thrice daily for 20 days orally (sobrerol group). The efficacy parameters were: sputum characteristics and volume, difficulty in expectorating, cough, dyspnoea, pulmonary auscultation. Tolerability was monitored and adverse events were reported. RESULTS: The study highlighted that neltenexine has a good efficacy in the treatment of patients with obstructive airways disease entailing significant impairment of clinical parameters. CONCLUSIONS: Neltenexine can be an effective therapeutic alternative to sobrerol.

Administration, Oral↗
PubMed1998

[Effects of processing on toxicity and pharmacological action of flos Genkwa].

Daphne genkwa can not be taken unless the toxicity is removed. The study on the effect of processing on the toxicity and pharmacological action of Flos Genkwa has shown that the toxicity of vinegar-processed Flos Genkwa is lower than that of the rude drug, but the pharmacological action is better. Both genkwanin and its vinegar-processed imitation have antitussive and expectorant actions without marked difference in efficacy. Both yuanhuacine and its vinegar-processed imitation could cause contraction of the extracorporeal womb and the intestinal canal, and the efficacy is almost similar in the concentration of 1:10(-5)-10(-6). The gestational womb was observed more sensitive than the normal one.

Animals↗
PubMed2002

["Neoceader" contains nicotine. A report of two user's nicotine addiction].

"Neoceader smoking" is widely marketed in drug stores as an over the counter expectorant for cigarette smokers in Japan. Using high-pressure liquid chromatography, we determined that one piece of Neoceader (3 cm) contains 0.79 mg of nicotine, which is equivalent to one-sixth of the amount of nicotine in one Japanese cigarette (Mildseven extra-light, Mildseven super-light, or Sevenstar). Two patients who had switched from cigarette smoking to Neoceader smoking, subsequently became addicted to nicotine. The continine concentration in their urine were 937 ng/ml and 2,724 ng/ml, respectively. These findings demonstrate that Neoceader contains nicotine and that its use can lead to nicotine addiction.

Adult↗