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Sinusitis--inspecting the causes and treatment.

In summary, sinusitis is a common disease caused by viruses, bacteria and the accumulation of excessive secretions and inflammatory mediators that impair the function of the mucociliary transport. Combination treatment is usually necessary to treat the cause and relieve the symptoms of sinusitis. Therapy aims at eliminating causative bacteria with antibiotics, decongesting edematous membranes, and thinning mucus with use of a mucolytic-expectorant. Improving the rheology of mucus by thinning abnormally thickened secretions may improve mucociliary transport and enhance penetration of antibiotics. Acute sinusitis usually responds to treatment within 2 weeks. However, if treatment is unsuccessful or a severe complication occurs, intravenous antibiotics may be necessary along with antral puncture and lavage. In resistant cases, an appropriate surgical procedure may enhance the drainage.

Acute Disease↗

[Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology].

To assess the immunoclinical effectiveness of a biological response immunomodulator, we used AM3 (glycophosphopeptide ), a glucomannan polysaccharide extracted from the cell wall of a strain of Candida utilis, in 20 children with asthmatic bronchitis. They received 2 envelopes (1 g) daily for 4 months. The results were compared with a control group of 20 untreated children with the same pathology. The following clinical and immunological parameters were assessed in all of them: cough, dyspnea, expectoration, frequency and intensity of the bronchospasm, time of administration of the symptomatic medication, and the delayed cutaneous cells response by means of the intradermal reaction of 5 antigens (Trichophyton, Candida albicans, tuberculin, E. coli and bacterial antigens). In the treated group, the immunoferon (AM3) reduced the symptoms, the intensity and frequency of the bronchospasm, and the symptomatic medication (table I, II and III). In basal conditions, the 40 children presented a state of 75% anergy; after 4 months of treatment, the treated group experienced a 45% decrease in their anergic situation, variation which was statistically significant when compared with the control group. In our 20 treated patients, AM3 behaved like and immunostimulant, improving the clinical situation and progress in patients with infectious respiratory disorders. We consider that the immunoferon constitutes a coadjuvant therapy to bacterial immunotherapy.

Anti-Bacterial Agents↗

[Effect of saibokuto on mucociliary transport system in the airway--basic and clinical assessments].

We studied the effects of Saibokuto, an antiasthmatic agent, on the airway mucociliary transport system. The addition of Saibokuto to a Rose chamber containing rabbit cultured tracheal epithelium dose-dependently increased ciliary beat frequency (CBF) as assessed by a photoelectric method: the maximal increase from the baseline value was 31.5 +/- 5.2% (p less than 0.001) and the concentration of Saibokuto required to produce a half-maximal effect (EC50) was 10(-4) mg/ml. This effect was not affected by the beta-adrenergic receptor antagonist propranolol or Ca(2+)-free medium, but was inhibited by the cyclooxygenase inhibitor indomethacin. Intracellular cyclic AMP levels were increased from 45.6 +/- 8.2 to 72.1 +/- 12.6 pmole/mg protein by 1.0 mg/ml Saibokuto (p less than 0.05). Thus, Saibokuto enhances ciliary motility probably through the synthesis of cyclooxygenase products and cyclic AMP. Additionally, administration of this drug to patients with chronic bronchitis, asthma and bronchiectasis improved their problems with sputum expectoration and reduced the amount of daily sputum (p less than 0.001). Therefore, Saibokuto may be of value in the treatment of patients with impaired mucociliary transport function in the airway.

Animals↗

Mucolytic effects of domiodol in tracheostomized patients after total laryngectomy. Double-blind, placebo-controlled, randomized pilot study with four-month follow-up.

The results obtained in a controlled clinical trial aimed at evaluating the efficacy and tolerability of a mucolytic treatment in laryngectomized patients are described. Domiodol (Mucolitico Maggioni, CAS 61869-07-6), an organic iodinated mucolytic agent, was given at the dosage of 60 mg t.i.d. to 20 patients in the post-operative period after laryngectomy (average 2 weeks in hospital and 4 months follow-up at home). A matched series of patients received a placebo during the hospital period and no treatment after discharge. The patients receiving the active treatment showed a statistically and clinically significant improvement of respiratory parameters (cough intensity, sputum quantity, sputum quality, expectoration difficulty). Such improvement was earlier and greater than that observed in the placebo-treated patients. It is concluded that a mucolytic treatment may be helpful in the post-operative treatment of laryngectomized patients with permanent tracheostomy.

Aged↗

Spontaneous dissolution of a guaifenesin stone.

Guaifenesin is a commonly used expectorant whose use may lead to the occasional formation of guaifenesin urinary stones. We herein describe a patient who was taking 2400 mg Guaifenesin per day as part of his treatment for asthma. He had a past history of a guaifenesin stone removed ureteroscopically. His current presentation was with a 9 mm by 6 mm stone in the upper left ureter, seen on CT scan, and treated initially with a ureteral stent and hydration. After 3 weeks, the stone had disappeared, as confirmed by repeat CT scan. The genesis and treatment of guaifenesin stones is discussed.

Adult↗

Infant deaths associated with cough and cold medications--two states, 2005.

Cough and cold medications that contain nasal decongestants, antihistamines, cough suppressants, and expectorants commonly are used alone or in combination in attempts to temporarily relieve symptoms of upper respiratory tract infection in children aged <2 years. However, during 2004-2005, an estimated 1,519 children aged <2 years were treated in U.S. emergency departments for adverse events, including overdoses, associated with cough and cold medications. In response to reports of infant deaths after such events, CDC and the National Association of Medical Examiners (NAME) investigated deaths in U.S. infants aged <12 months associated with cough and cold medications. This report describes the results of that investigation, which identified deaths of three infants aged <6 months in 2005, for which cough and cold medications were determined by medical examiners or coroners to be the underlying cause. The dosages at which cough and cold medications can cause illness or death in children aged <2 years are not known. Food and Drug Administration (FDA)-approved dosing recommendations for clinicians prescribing cough and cold medications do not exist for this age group. Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children aged <2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting health-care provider and should follow the provider's instructions precisely. Clinicians should use caution when prescribing cough and cold medications to children aged <2 years. Moreover, clinicians should always ask caregivers about their use of over-the-counter combination medications to avoid overdose in children from multiple medications that contain the same ingredient.

Analgesics, Non-Narcotic↗

[Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate administered by aerosol in adult patients with catarrhal pathology of otorhinolaryngologic origin].

The test has been performed on 20 patients, aged between 14 and 68 suffering from a catarrhal pathology of otorhinolaryngologic nature for which a mucolitic aerosol therapy was recommended. 4-carbomethoxythiazolidine has been administered with a posology of one bottle twice a day (by aerosol-nebulization) for periods of time ranging from 4 up to 15 days. Together with the 4-carbomethoxythiazolidine treatment, some patients have been administered concomitant drugs. At the end of the tests the development of the most significative symptomatologic parameters has been analysed according to the Wilcoxon test: quantity, kind and characteristics of nasal secretions, nasal obstruction, phlogosis of the nasal and pharyngeal mucosa, hoarseness, difficulty in catarrhal expectoration, hypoacusia, retraction of the tympanic membrane. The final clinic evaluation of the efficacy of 4-carbomethoxythiazolidine, expressed according to the examination of the achieved clinic result, has been "positive" in 17 cases (85%) and "negative" in 3 cases (15%). As for its tolerance, in no case has 4-carbomethoxythiazolidine caused detectable side-effects.

Adolescent↗

[Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in a double-blind crossover experiment on chronic obstructive bronchopneumopathy].

The Authors describe a test performed on 20 hospitalized patients aged between 22 and 80, suffering from obstruent chronic broncho-pneumopathy. The test has been performed according to a double-blind pattern; each patient has been treated according to the 10-day long randomized scheme with one of the two drugs N-acetyl-L-cysteine, 4-carbomethoxythiazolidine. After a 7-day wash-out the patient has been treated with the other drug for a further period of 10 days. All patients have been administered both products at a dosage of 200 mg. three times a day. Every day following values have been registered: arterial pressure, body temperature; subjective and objective symptomatology relieves: cough, cephalea, asthenia, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea. Furthermore before and after the treatment the quantity and the quality of the expectorate in order is evaluate the biologic tolerance of the examined drugs, before and after each treatment the following haematochemical and urinary tests have been performed: VES, azotemia, glycemia, SGOT, SGPT, LDH, alkaline phospatase, total and direct bilirubinaemia, prothrombinic activity, complete chemical analysis of urines. As shown in Tab. I-IX, a global analysis of the results proves that 4-carbomethoxythiazolidine is a very well-tolerated drug without any negative side-effect. As far as its therapeutic efficacy is concerned we can say that the mucolitic activity of 4-carbomethoxythiazolidine is the some of that of N-acetyl-L-cysteine.

Acetylcysteine↗

[Efficacy and tolerability of paracetamol-sobrerol combination in patients with hyperpyrexia].

The therapeutic efficacy and tolerability of the association paracetamol-sobrerol in comparison with paracetamol alone, was tested in a double-blind, randomized clinical trial, carried out on 287 out-patients, suffering from diseases of the respiratory tree with fever. The treatment was performed for up to five days. At the end of the treatment, both treatments lead to an important improvement of all considered clinical parameters; furthermore, the association paracetamol-sobrerol showed a statistically important difference versus paracetamol alone as to cough and difficulty to expectorate. As to body temperature, both paracetamol and paracetamol-sobrerol showed a good antipyretic activity; furthermore, the association compared to paracetamol alone obtained a statistically significant differences in times x treatments. These data fully confirm the results obtained from recent studies: the simultaneous administration of paracetamol and sobrerol obtains a better antipyretic action than paracetamol alone. This synergism allows to reduce paracetamol doses and, consequently, to eliminate the already low incidence of adverse reactions, without decreasing the antipyretic activity.

Acetaminophen↗

[Pharmacological studies on dingchuanning].

Dingchuanning has been found to increase markedly the perfusion of isolated lung of guinea-pig. It may produce a relaxing effect on the smooth muscles of the isolated trachea, bronchus and lung strips of guinea-pigs, as well as a prominent protective effect on the bronchial asthma induced by inhalation of bronchoconstrictors in conscious guinea-pigs. It also has significant expectorant and antianaphylactic effects and helps to inhibit markedly the SRS-A release from lung tissues and to counteract directly the activity of SRS-A.

Animals↗

[Effectiveness and tolerance of a new molecule with secreto-dynamic activity: nesosteine].

232 patients with acute or chronic respiratory disorders characterized by increased secretion, were included in an open multicentre trial to evaluate the tolerability and the activity of a new molecule with secreto-dynamic action, nesosteine. The drug was administered orally at the dose of 900 mg/day for two consecutive weeks. The incidence of side effects (11.6%) was comparable to that observed in studies carried out on molecules with similar activity. Undesirable reactions were found mainly at the gastrointestinal level. Side effects were slight/moderate in most cases; only 3 patients abandoned treatment. Nesosteine therapeutic activity was highly valid; cough and expectorate were favourably affected by treatment. The drug, by restoring the natural characteristics of excreate viscoelasticity, favored a better mucociliary clearance and a more incisive cough expelling action. The activity/tolerability ratio was judged excellent/good by the investigator in 83% of the patients treated.

Adult↗

Secretomotor and mucolytic effects of mabuterol, a novel bronchodilator.

Action of mabuterol, a novel bronchodilator, on the respiratory secretion system was investigated, and the following effects were confirmed: 1) increase of output volume, amounts of protein and pulmonary surfactant in respiratory fluid; 2) decrease of sputum viscosity; 3) fragmentation of the sputum structure and 4) promotion of the mucociliary transport of particles. The results in the present study may, at least partly, substantiate clinical efficacy such as improvement of pulmonary function, favourable effects on expectoration and amelioration of symptoms observed in patients with chronic obstructive pulmonary disease.

Adrenergic beta-Agonists↗

[Pharmacotherapy of cough].

The optimal approach to the treatment of cough consists, first, in determination of its precise cause. Treatment should be directed at the specific etiology or the pathophysiologic mechanism responsible for cough. The outcome of specific treatment is almost always successful. However, there are also situations in which the cause of cough is unknown or in which the cough does not serve any useful purpose but prevents rest and sleep. In such cases symptomatic treatment with antitussives may be indicated. Centrally acting antitussives such as opium alkaloids, dextromethorphan and noscapine are the most effective drugs. The indication for expectorants lacks scientifically based support.

Anesthetics, Local↗

Management of mucus hypersecretion.

Mucus hypersecretion (greater than 25 ml/day) is commonly seen in chronic bronchitis, whereas bronchorrhea (greater than 100 ml/day) is found in other conditions (e.g. asthma, bronchiectasis, alveolar-cell carcinoma). Clearance of secretions can be improved by physical and pharmacological methods. Cough airways obstruction--for "two-phase air-liquid flow". Chest physiotherapy (the forced expiration technique, FET, and postural drainage, PD) is effective in clearing central and peripheral secretions and can be self-employed. Oral high frequency oscillation (OHFO) at 13 Hz is a useful adjunct. Beta-adrenergic drugs improve clearance and this is not entirely to their bronchodilator activity. Likewise methylxanthines enhance clearance particularly in central airways. Corticosteroids are effective in bronchorrhoea and asthma. Anticholinergics may control hypersecretion. Mucolytics and expectorants are used traditionally but their activity is difficult to prove. Hypertonic (7%) saline is useful--as is cromoglycate in asthma.

Adrenal Cortex Hormones↗

Pharmacological study of the new mucolytic drug N-guanyl-cysteine.

The pharmacological evaluation of N-guanyl-cysteine (IQB-782) is reported. This new cysteine derivative shows a potent mucolytic-expectorant activity in different test systems. Thus, IQB-782 protects rats against tobacco-smoke-induced respiratory airway obstruction, increases the tracheo-bronchial mucus secretion in rabbits and increases the pulmonary excretion of fluorescein in mice, an index of broncho-secretagogue activity. Like other mucolytics, IQB-782 is also effective in vitro in reducing the viscosity of a suspension of gastric mucin. This new drug is apparently devoid of any cardiovascular or autonomic activity and shows a moderate CNS depressant effect. IQB-782 is consequently a new thiol derivative which may offer some advantages in the treatment of different types of obstructive pulmonary disease.

Animals↗

[Recent aspects of pharmacotherapy in obstructive airway diseases with special regard to bronchial asthma (author's transl)].

After demonstration of the pathophysiologic principles bronchial obstruction a review of the pharmacotherapeutic possibilities is presented. The main of therapeutics comprehends beta-2-receptor stimulants in combination with theophylline derivatives. Further therapeutic efforts with anticholinergic drugs (ipratropium bromide) preponderant in chronic bronchitis or intrinsic bronchial asthma respectively and with cromolyn sodium in extrinsic asthma are valuable. Glucocorticoids are allowed to be given only after exhaustion of all other modes of treatment, if possible as intermittent long term treatment. The stimulation of expectoration is an essential part of pharmacotherapy. The complex application of less specific methods of pharmacotherapy and physiotherapy belongs to the comprehensive treatment of patients. The threatening life asthmatic status demands the appropriate use of all possibilities of pharmacotherapy and intensive care if necessary.

Adrenergic alpha-Antagonists↗

Drug effects on mucociliary function.

We summarize the findings of 18 clinical studies carried out over a decade to ascertain the effect of 14 pharmacological agents on lung mucociliary clearance. These studies were carried out on a total of 172 subjects/patients and amounted to 443 individual assessments. The objective, in vivo radioaerosol technique was used to measure clearance. Bromhexine, aerosolized hypertonic saline and aminophylline enhanced the clearance of lung secretions. There was some indirect evidence of a speeding up of mucociliary clearance following the administration of prednisolone and the synthetic anticholinergic bronchodilator ipratropium, while hyoscine was found to reduce clearance. There was no effect on clearance of single doses of the beta blockers propranolol and atenolol, the beta 2 adrenergic drug terbutaline, the cholonergic drug bethanecol and the expectorants 2-mercapto-ethane-sulphonate (aerosol) and glycerol guaiacolate. Long term administration (4 - 7 days) of the beta 2 adrenergic drugs terbutaline and clenbuterol also failed to show any effect on lung mucociliary function.

Adrenal Cortex Hormones↗