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)

Drug interactions common to all angiotensin-converting enzyme (ACE) inhibitors include those with thiazide diuretics and other antihypertensive agents. Interactions involving specific ACE inhibitors include captopril-digoxin, resulting in decreased clearance of digoxin from plasma in patients with heart failure, and captopril-probenecid, causing a decrease in captopril clearance. Tissue kinins, such as bradykinin, are metabolised by ACE inhibitors. Interactions involving bradykinin include captopril-indomethacin, in which an attenuation of the antihypertensive effects of captopril is manifest. Interestingly, neither enalapril nor lisinopril appear to show this interaction with indomethacin. Kinin-based interactions may also be important in the genesis of ACE inhibitor-induced cough and skin rash. Renal dysfunction affects the pharmacokinetics and pharmacodynamics of all ACE inhibitors, necessitating dosage reduction. Hepatic impairment is of less clinical importance, causing a delay in the onset of action of enalapril with initial doses, but probably having little relevance to long-term therapy.
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PMID:Drug interactions with ACE inhibitors. 267 38

Prostaglandins may cause hyperresponsiveness to bronchoconstrictor agents in the lung and hyperalgesia in the skin. Increased airway concentration of both prostaglandins and bradykinin has been suggested as the possible cause of the increased cough sensitivity sometimes found in patients with cough associated with taking drugs that inhibit angiotensin-converting enzyme. We have therefore investigated the effect of prostaglandin E2 (PGE2), bradykinin (BK), histamine (H), and citric acid (C) on capsaicin-induced cough and increase in respiratory resistance (Rrs). Capsaicin-induced changes in Rrs and dose-cough response were measured before and after inhaling 0.76 mumol of PGE2, BK, H, and C. All the test substances caused cough, which was subject to tachyphylaxis, but no significant change in Rrs. Neither BK, H, nor C altered the capsaicin cough or Rrs response. However, PGE2 significantly increased both responses to capsaicin, the geometric mean (95% Cl) for the dose of capsaicin causing 5 or more coughs being 16.2 (14.3 to 18.3) nmol before and 4.4 (2.4 to 7.9) nmol after PGE2 (p less than 0.05). The percent increase (95% Cl) in Rrs after capsaicin was 20 (16.5 to 23.5)% before and 37.2 (32.2 to 43.2)% after PGE2 (p less than 0.05). The results suggest that the cough reflex will be increased in the presence of PGE2 in the airway.
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PMID:Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine. 275 Nov 60

In six normal subjects treatment with 4 mg nedocromil sodium failed to alter the cough and bronchoconstriction induced by inhaled capsaicin. Because nedocromil has previously been shown to inhibit reflex bronchoconstriction provoked by inhaled sulphur dioxide and inhaled bradykinin, the results suggest that inhaled capsaicin acts on different nerve fibres.
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PMID:Effect of nedocromil sodium on the airway response to inhaled capsaicin in normal subjects. 285 81

Thirty three reports of cough associated with captopril and 26 associated with enalapril received by the New Zealand intensive medicines monitoring programme were reviewed. The programme is a specialised part of the New Zealand postmarketing surveillance system. Review of these reports showed that the cough was an adverse reaction to the drugs, occurred even with low dose treatment, and was severe enough to warrant withdrawal of the drugs in most of the cases reported. A significant sex difference was shown, with women predominating. The reaction seemed to be a greater problem with enalapril, and in seven patients it occurred with both captopril and enalapril. Withdrawal of treatment resulted in rapid recovery, and no long term effects were shown. The pathogenesis of the reaction is unknown, but possible mediators include bradykinin and prostaglandins.
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PMID:Cough associated with captopril and enalapril. 303 57

Cough is most often a reflex act elicited by the stimulation of nervous receptors in the respiratory tract. The most important tussigenic areas are at the level of the larynx and the more distal portion of the trachea with its bifurcation. Laryngeal rapidly adapting receptors with myelinated fibres are promptly activated by tussigenic stimuli, but it is unlikely that they are the only ones responsible for laryngeal coughing. In fact, some evidence supports the involvement of laryngeal C-fibre receptors. Cough in response to inhalation of aqueous aerosols containing low chloride concentrations may involve the same category of receptors with myelinated fibres that mediate apnoea in the newborn. Within the tracheobronchial tree, there are rapidly-adapting irritant receptors responsive to several tussigenic stimuli and concentrated at tussigenic sites. Animal species without this type of ending do not cough. However, some results for the tracheobronchial tree suggest a role for other types of receptors. Slowly adapting stretch receptors may play an indirect role through their stimulatory effect on expiratory muscles. A role for C-fibre receptors is proposed considering the activation of these endings by substances (capsaicin, lobeline, bradykinin, SO2) capable of inducing cough. Bronchial C-fibre receptors, present also in proximal airways, respond to light mechanical probing. Contrary to an involvement of pulmonary C-fibres is the observation that cough is not part of the lung chemoreflex, although during this reflex syndrome (apnoea followed by rapid and shallow breathing, bradycardia and hypotension) cough can be induced by mechanical irritation of the trachea.
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PMID:Afferent pathways for the cough reflex. 331 Dec 41

Water and secretions interact in airways to produce the sol and gel layers that allow for entrapment of foreign materials and subsequent clearance by ciliary movement and by cough. Active Cl ion transport produces fluid, and this process is activated by products of mast cells (leukotrienes), eosinophils (major basic protein), and by other inflammatory mediators (prostaglandins, bradykinin). Gland secretions produce the bulk of the volume of secretions. Airway irritation stimulates gland secretion reflexly via vagal muscarinic pathways. Recently, the sensory nerves have been discovered to release substance P and other neuropeptides when the airways are irritated. The stimulatory effects of neuropeptides on gland secretion (and on other inflammatory sites) are modulated by enkephalinase a membrane-bound enzyme that cleaves neuropeptides and thereby inactivates them. Up- or down-regulation of enkephalinase is predicted to change the degree of inflammatory response to neuropeptides. Finally, the cell surface of airway epithelial cells have been discovered to secrete large molecular weight glycoconjugates; these secreted products are increased markedly by a series of proteinases produced by inflammatory cells (neutrophils, mast cells) and by bacteria. Their exact physiologic roles are still unknown but they may contribute to the bulk and viscoelastic properties of airway secretions, and they may serve an important role in bacterial, viral and inflammatory cell adhesion.
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PMID:Secretion and ion transport in airways during inflammation. 333 78

Regarding 5 recent cases of cough induced by inhibitors of angiotensin conversion enzyme (CEI), the authors emphasize the still underestimated frequency of this annoying and sometimes disabling side-effect (10 to 15% of cases). They remind of their clinical and evolutive characteristics: dry cough, predominantly at night, often occurring rapidly, sometimes delayed (up to 17 months) after introduction of the CEI and unrelated to the dosage. The cough usually disappears in two to three days (up to 8 days) upon discontinuation of the treatment. The test of discontinuation-reintroduction, possibly crossed (captopril/enalapril) is used in questionable cases as a diagnostic test. Besides, this diagnosis must be made rapidly in order to avoid costly, unnecessary laboratory tests which are sometimes unpleasant for the patient. The cough could be explained by an irritation of the bronchial mucosa secondary to bradykinin and pulmonary E2 prostaglandins elevation, under CEI.
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PMID:[Cough and inhibitors of the angiotensin-converting enzyme]. 340 97

The effect of bradykinin was studied by inhalation in normal and asthmatic human subjects, as well as on human bronchial smooth muscle in vitro. Bradykinin caused cough and retrosternal discomfort in all subjects and bronchoconstriction in asthmatic subjects. Bradykinin was approximately 10 times more potent than histamine and methacholine, and there was a significant correlation between the subjects' sensitivity to histamine and bradykinin. Bradykinin-induced bronchoconstriction was prolonged when compared with that of histamine and the C-fiber stimulant capsaicin. This bronchoconstriction was subject to tachyphylaxis, which was also associated with desensitization of the subjects to inhaled histamine. The provocative dose causing a 35% fall in specific airway conductance (PD35) was unaffected by aspirin (1 g orally). However, ipratropium bromide (0.25 mg by nebulizer) significantly inhibited the effect of bradykinin, the PD35 being 0.8 mumol (range, 0.16 to 3.4) and 0.15 mumol (range, 0.047 to 1.15) after active dose and placebo, respectively (p less than 0.05). Likewise, cromolyn sodium (40 mg dry powder) also significantly reduced response to bradykinin, with a PD35 of 0.04 mumol (range, 0.13 to 0.31) after placebo and 0.39 mumol (range, 0.05 to 4.45) after SCG (p less than 0.05). Bradykinin only weakly constricted human bronchial smooth muscle in vitro. Bradykinin at 10(-4) caused only 21.5 +/- 5.5% of the maximal carbamylcholine contraction in 11 of 18 airways. Captopril did not enhance the effect of bradykinin. Bradykinin is a potent bronchoconstrictor of human airways in vivo, acting in part through cholinergic mechanisms but not because of the formation of prostaglandins.
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PMID:Bradykinin-induced bronchoconstriction in humans. Mode of action. 354 15

Reflex bronchoconstriction can be induced by mechanical and chemical stimuli to the respiratory tract, especially from the larynx down to the larger intrapulmonary airways. The pathways for these reflexes have been analysed in experimental animals. The afferent nerves include fibres from rapidly adapting ("irritant") receptors in and under the epithelium of the airways, and those from "C-fibre" receptors in the tracheobronchial tree and possible alveoli. Many of the mediators thought to be released in lung antigen antibody reactions and airway tissue damage can be shown to activate these groups of sensory receptors: the mediators include prostaglandins, bradykinin, histamine and 5-hydroxytryptamine. Both the irritant and the C-fibre receptors have been shown to cause reflex bronchoconstriction, as well as other reflex motor actions that influence the diameter of the respiratory tract, such as mucus secretion and laryngeal constriction. They are also responsible for respiratory changes, including coughing. Mediators which are released in bronchial asthma are potential agents in setting up reflex bronchoconstriction. In man the evidence for such a reflex depends primarily on the inhibitory efficiency of atropinic drugs in some forms of asthma. Such evidence cannot be completely unequivocal but, taken with the analogy with animal experiments, there seems to be a prima facie case for reflex bronchoconstriction as one component of the total pattern of an asthma attack.
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PMID:Mediators and reflex bronchoconstriction. 636 Jul 1

Bradykinin is released in the lungs in asthma and pulmonary anaphylaxis. It has negligible direct bronchoconstrictor effects in humans or dogs, but inhaled as aerosol it causes cough and reflex bronchoconstriction in asthmatics and some normal subjects. The afferent nerves responsible for these reflex effects have not been identified. We recorded vagal impulses in anesthetized dogs to determine whether lung afferents were stimulated by bradykinin. C-fiber endings in the intrapulmonary airways accessible from the systemic circulation were stimulated by bradykinin injected into the left atrium (0.5-1.0 micrograms/kg) or bronchial artery (1.5 micrograms), activity increasing 15-fold on average. C-fiber endings accessible from the pulmonary circulation were relatively insensitive to bradykinin. Bradykinin caused a small increase in firing of some rapidly adapting (irritant) receptors, but the effect appeared to be secondary to vascular changes. Bradykinin had variable effects on slowly adapting stretch receptors, but did not stimulate them directly. Thus vagally mediated sensory or reflex effects initiated by bradykinin in the lung are probably due to stimulation of "bronchial" C-fibers.
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PMID:Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs. 737 22


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