Bronchodilator Properties Research Articles

Bronchodilator properties of inhaled clemastine

Bronchodilator properties of inhaled clemastine

SELECTIVITY OF β‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON BRONCHIAL, SKELETAL, VASCULAR AND CARDIAC MUSCLE IN THE ANAESTHETIZED CAT

1 The potencies of fifteen beta-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The beta-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 mug/kg and maximal or near maximal responses were produced by 0.3-1 mug/kg. Trimetoquinol was also an essentially unselective agonist. 3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist - AH 7616 (4-hydroxy-alpha1-[[(1-methyl-3,3-diphenyl-propyl)amino]-methyl]-m-xylene-alpha1, alpha3-diol, acetate) - was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its beta-adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The beta-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of beta-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual beta-adrenoceptor sub-classification.

Sodium cromoglycate (cromolyn sodium): a review of its mode of action, pharmacology, therapeutic efficacy and use.

Synopsis Sodium cromoglycate (cromolyn sodium; FPL 670)2 is a synthetic bischromone derivative advocated for use in the prophylaxis and adjunctive management of bronchial asthma. It is not intended for the treatment of acute attacks. Sodium cromoglycate does not possess direct anti-inflammatory or bronchodilator properties, but when inhaled prior to antigen bronchial challenge in asthmatic subjects it inhibits at least partially, the development of an allergic bronchial reaction. Sodium cromoglycate is believed to act by stabilisation of mast cell membranes, thereby inhibiting the release of pharmacological mediators of anaphylaxis when the cells are triggered in a selective manner. In experimental studies in allergic subjects, sodium cromoglycate has been shown to inhibit the development of both immediate and late antigen-induced asthmatic reactions; in contrast, corticosteroids whether given orally or by inhalation, inhibit only the late response. Numerous short-term controlled therapeutic trials have demonstrated the superiority over placebo of prophylactically administered sodium cromoglycate in children and adults with bronchial asthma. Most long-term trials have not been placebo controlled, but in the few that have, sodium cromoglycate has controlled symptoms over a long period when used in conjunction with conventional antiasthmatic therapy. Allowing for those responding to placebo, about 50% of patients given sodium cromoglycate have been adequately controlled by the drug. The degree of symptomatic improvement in asthma symptoms has varied considerably between studies and individuals, and objective evidence of improvement has sometimes been minimal or absent in patients who improved subjectively. These variations may be related to trial design and to the varied clinical characteristics of the study population. Prophylactic sodium cromoglycate is of considerable benefit to a few patients and of some benefit to many. Young patients, who, between moderate to severe attacks of asthma are relatively free from symptoms, often respond. There is a tendency towards a more frequent response in patients with strong evidence of allergy in whom allergy is a dominant causative factor in their asthma, and in patients in whom the drug produces considerable amelioration of post-exercise airways obstruction, but there is still no clear indication of how to select those who will benefit most from treatment. The absence of demonstrable allergy does not preclude a favourable response, just as its presence does not ensure one. Sodium cromoglycate therapy may permit a gradual and careful reduction in maintenance dosages of corticosteroids or their complete withdrawal in a few patients. Side-effects have generally been infrequent, mild and transient; local irritation of the throat and trachea having been reported most frequently. Skin rash has occurred rarely. In long-term studies in man there has been no evidence of sodium cromoglycate having caused radiological changes in the lungs, or any renal, hepatic or haematological abnormalities.

Cromolyn prophylaxis for chronic asthma.

Editorial Notes1 June 1973Cromolyn Prophylaxis for Chronic AsthmaJOHN S. HYDE, M.D.JOHN S. HYDE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-6-966 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince 1965 cromolyn sodium* has been subjected to extensive pharmacological and clinical investigation in animals and man. The drug has no intrinsic bronchodilator, antihistaminic, or steroid-like properties. It appears to act by protecting the mast cell membrane and inhibiting the release of spasmogenic mediators that occur during antigen-antibody reactions and when triggered by certain seemingly nonimmunological mechanisms, such as exercise or hyperventilation (1).In the treatment of asthma, cromolyn sodium is given by inhalation, by a capsule containing 20 mg of drug per dose, in a special turbo-inhaler device, the Spinhaler. A recent study has further clarified the fate of...

Bronchodilating properties of the prostaglandin F 2β in the guinea pig and cat

The bronchodilating properties of PGF 2β (a stereo-isomer of the naturally occurring bronchoconstrictor (PGF 2α) are described in the guinea pig and cat. The possible physiologic implications of this finding are discussed.

Inhibition of cyclic 3′,5′-adenosine monophosphate phosphodiesterase by substituted imidazopyrazines

5-Chloro-6-(ethylamino)-1,3-dihydro-2H-imidazo[4,5- b]pyrazin-2-one (CE-IP), a new compound with bronchodilator, cardiac stimulant and peripheral vasodilatory properties was found to be approximately two to five times more potent than theophylline as an inhibitor of cyclic AMP phosphodiesterase from several sources. CEIP stimulated lipolysis in isolated fat cells and was synergistic with norepinephrine in increasing glycerol release and the accumulation of [ 14C] cyclic AMP from adenine8- 14C pre-labeled fat cells. CEIP vivo produced up to a 10-fold increase in the cyclic AMP content of rat heart. While imidazopyrazines with a secondary amine substituent on position 6 were in general relatively potent phosphodiesterase inhibitors, substituents with a more basic character resulted in decreased enzyme inhibitory activity. 5-Chloro-6-[[2-(dimethyl-amino)ethyl] amino]-1,3-dihydro-2H-imidazo[4,5- b]pyrazin-2-one (CDIP) was less active than theophylline as a phosphodiesterase inhibitor but was nearly as active as theophylline in potentiating norepinephrine-stimulated lipolysis and cyclic AMP accumulation in isolated fat cells. CDIP in vivo has peripheral vasodilatory and bronchodilatory activity but is distinct from theophylline and CEIP in that it does not cause tachycardia.

SALBUTAMOL: A DOUBLE‐BUND CROSSOVER TRIAL

Thirty-one patients with different types of obstructive airways disease participated in a double-blind cross-over trial comparing equipotent doses of isoprenaline, 1,000 μg, orciprenaline, 1,500 μg, salbutamol, 200 μg, and a normal saline placebo. The solutions were administered as aqueous aerosols, using a Wright nebulizer. Bronchodilator properties were assessed using spirometry and the peak expiratory flow rate. Cardio-vascular responses were assessed by changes in the radial pulse rate. Salbutamol appears to have similar bronchodilator properties to Isoprenaline and orciprenaline, there being no statistically significant difference between the responses. The dose of salbutamol, weight for weight, which produces a similar bronchodilator response is much less than that of isoprenaline or orciprenaline. Cardio-vascular responses were variable, there being no statistically significant difference between salbutamol, isoprenaline, orciprenaline and the saline placebo.

Pharmacological significance of biogenic amines in the lungs: noradrenaline and dopamine.

1. The noradrenaline concentration in the lung was less than 0.5 mug/g in eight animal species.2. In the cat, dog, rabbit and goat, tyramine produced a fall in pulmonary resistance, which was reduced by the administration of either reserpine or cocaine. Although an infusion of noradrenaline increased the content of this amine in the lung of the cat, previously depleted by reserpine, the bronchodilator property of tyramine was not restored. The infusion of isoprenaline did not restore the response to tyramine. The role of either catecholamine in mediating the bronchomotor response to tyramine could not be ascertained.3. The concentration of dopamine was as high as 6.4 mug/g in the goat lung and less than 0.5 mug/g in the lungs of the cat, rabbit, dog, rat, mouse, guinea-pig and man. Dopamine, injected intravenously into the cat, dog, rabbit and goat, produced a slight rise in pulmonary resistance. This increase was blocked by tolazoline, indicating that the response was mediated by alpha-adrenoceptors in the bronchial passages. No procedure has been observed to influence the dopamine content of the lung. The release of dopamine cannot, however, be excluded until the blood in the bronchial veins has been analysed.

Ventilatory effects of “thermo-Fog” as a bronchodilator vehicle

Summary 1. Fifty patients, 42 men and 8 women, of ages 18 to 71 years, with chronic bronchitis, bronchial asthma, and chronic diffuse obstructive pulmonary emphysema, had pulmonary function studies performed before and immediately after a 15-minute inhalation of isoproterenol-HCl, a sympathomimetic drug with bronchodilator properties, in a super-heated mixture (“Thermo-Fog”) of 40 per cent. propylene glycol in isotonic saline. 2. Vital capacity, F.E.V. 1 maximum minute ventilation, vital capacity time and Breathing Reserve Ratio were the indices chosen for examination. 3. This therapy resulted in a significant enhancement of the average maximum minute ventilation and shortening of the vital capacity time, with less definite effects upon the group average vital capacity, breathing reserve ratio and timed 1-second vital capacity values. 4. Sixty per cent. of the patients showed individual vital capacity rises and 72 per cent. had individual rises in maximum minute ventilation figures. 5. There were no adverse clinical effects and the aerosol was well tolerated. 6. The super-heated aerosol, generated by a simple and inexpensive device, appears to be a suitable vehicle for administration of a bronchodilator drug.

Structure-activity relationships in a series of 6-thioxanthines with bronchodilator and coronary dilator properties.

The bronchodilator activity of 47 compounds on the isolated guinea-pig tracheal ring preparation and the coronary dilator activity on the dog heart-lung preparation is described. 1,3-Disubstituted xanthines and 6-thioxanthines (theophyllines and 6-thiotheophyllines) were more active as bronchodilators and as coronary dilators than were 3,7-disubstituted 6-thioxanthines (6-thiotheobromines) or 1,3,7-trisubstituted 6-thioxanthines (6-thiocaffeines). None of the 6-thioxanthines was of any interest as a diuretic and none of the 6-thiocaffeines was of any interest as a central stimulant. Structure-activity requirements for potent bronchodilator and coronary dilator activity are discussed.

The Effect of Xanthin Derivatives: Ro 1-8239, Aminophylline and Dihydroxy Theophylline on Chronic Pulmonary Disease

The widespread use of various xanthine derivates in chronic pulmonary disease have prompted numerous studies on the action of these drugs in both pulmonary function and cardiocirculatory system. It has been shown that aminophylline and dihydroxytheophylline (DHT) have bronchodilator properties”2 increasing ventilation by direct stimulation of the respiratory center.’ The object of the present study is to test the effect of various xanthinic compounds on the respiratory function of patients with chronic pulmonary disease, especially of the new compound Ro 1-8239 (X-D) .

Bronchodilator Activity of Three New Drugs in Patients with Pulmonary Emphysema

Many therapeutic agents have been employed effectively for the relief of bronchospasm. Preparations in current clinical use have been shown to be more efficacious than older ones, but no single agent has proved entirely satisfactory. Therefore, the present study was undertaken in order to evaluate the bronchodilator properties of three new drugs. As will be demonstrated, extensive preliminary observations showed that only one of these appeared to offer definite indications of therapeutic value. The bronchodilator activityof this drug was then studied in greater detail. PART I. Method Seventeen male patients of average age 59, with intrinsic asthma or hypertrophic emphysema with clinical evidence of associated bronchospasm were studied. Ventilometric measurements of vital capacity, maximum breathing capacity, volume of deep respiration, and breathing reserve were made with the Collins ventilometer. Although a number of additional tests were employed in this and other studies, these four appeared, in the experience of this laboratory, to provide a simple but reliable clinical measure of lung function. Observations on each subject were made on each of four separate days. The drugs studied, and their dosages, were as follows: 1) Paveril phosphateR** a papaverine analogue - 50 mg. 2) Antrenylzt anticholinergic - 1.0 mg. 3) Drug 1313,tt adrenergic - 10 mg. Amlnophylline, 0.5 Gm., was separately administered as a basis for comparison.