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)

The pharmacological mechanisms of allergic cough in the guinea pig were studied. Actively sensitized guinea pigs were exposed to aerosols of antigen to elicit coughing. In separate experiments, naive guinea pigs were exposed to aerosols of capsaicin to elicit coughing. Both allergic and capsaicin-induced cough were inhibited by loratadine (0.3-10 mg kg-1 p.o.) and chlorpheniramine (0.1-3.0 mg kg-1 p.o.). Neither cimetidine (10 mg kg-1 s.c.), nor thioperamide (3-10 mg kg-1 s.c.), inhibited allergic or capsaicin-induced cough. Codeine (3-30 mg kg-1 p.o.), salbutamol (0.003-3.0 mg kg-1 s.c.) and ipratropium (0.03-1.0 mg kg-1 s.c.) inhibited both allergic and capsaicin-induced cough. Hexamethonium (10 and 30 mg kg-1 s.c.) inhibited allergic, but not capsaicin-induced cough. Allergic and capsaicin-induced cough were unaffected by phenidone (5.0 and 10.0 mg kg-1 s.c.). Indomethacin (5.0 and 10.0 mg kg-1 s.c.) had no effect on allergic cough but slightly inhibited capsaicin-induced cough. We conclude that allergic and capsaicin-induced cough are modulated by histamine H1 receptor and cholinergic mechanisms. Histamine H2 or histamine H3 receptor mechanisms, and lipoxygenase and cyclooxygenase products of arachidonic acid metabolism do not influence allergic and capsaicin-induced cough. Ganglionic mechanisms play a minor role in the production of allergic cough and no role in capsaicin-induced cough.
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PMID:Pharmacological studies of allergic cough in the guinea pig. 749 4

Experiments were conducted to study the effect of the opioid, codeine, on different components of the cough motor pattern. Midcollicular decerebrate cats were paralyzed and artificially ventilated by a pump triggered by the phrenic neurogram. Inspiratory (phrenic) and expiratory (cranial iliohypogastric) neurograms were recorded. Fictive cough was produced by mechanical stimuli applied to the intrathoracic trachea. Codeine (0.03-1.0 mg.kg-1, i.v.) decreased cough frequency (average number of coughs per stimulus trial), expiratory burst amplitude, and inspiratory burst amplitude in a dose-dependent manner. The maximum reduction in cough frequency and expiratory amplitude produced by codeine was 80-90% for both parameters. However, codeine was more potent in reducing cough frequency (ED50 = 0.1 mg.kg-1) than expiratory burst amplitude (ED50 = 0.35 mg.kg-1). The maximum observed reduction of inspiratory burst amplitude elicited by codeine was approximately 40%. There was a positive linear relationship between phrenic and cranial iliohypogastric burst amplitudes during fictive cough (r = 0.82, P < 0.001). Codeine destabilized the motor pattern during fictive cough by disrupting this relationship between inspiratory and expiratory burst amplitudes. We conclude: (a) the central pattern generator for cough is functionally organized into a cough frequency generator, an expiratory burst amplitude generator and an inspiratory burst amplitude generator, each of which have different sensitivities to codeine (b) there exists a specific codeine-sensitive neural mechanism matching the relative magnitude of central drive to inspiratory and expiratory motoneurons during cough.
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PMID:Effect of codeine on the inspiratory and expiratory burst pattern during fictive cough in cats. 785 78

We studied the difference in the effects of codeine on coughs caused by mechanical stimulation to the larynx and to the bifurcation of the trachea in lightly anaesthetized guinea pigs. Mechanical stimulation to the larynx or the bifurcation of trachea caused a stable cough response. The response was reproducible over 60 min, when stimulation was repeatedly applied at 20-min intervals. No significant difference was found between the amplitudes of the responses to mechanical stimulation of the larynx and of the tracheal bifurcation. Codeine, 10, 20 and 50 mg/kg, dose dependently depressed the coughs caused by larynx stimulation. The antitussive, however, failed to depress the cough caused by stimulation to the tracheal bifurcation, although a large dose, 50 mg/kg, significantly depressed the cough. In capsaicin-treated guinea pigs, codeine at 20 mg/kg significantly depressed the cough caused by stimulation to the tracheal bifurcation. The present results suggest that cough caused by mechanical stimulation to the larynx might be more sensitive to codeine treatment than cough caused by stimulation to the bifurcation of trachea. Furthermore, it is suggested that coughs caused by mechanical stimulation to both sites might consist of at least two components as regards their pharmacological nature.
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PMID:Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea pigs. 921 89

Codeine is generally accepted as a standard or reference antitussive against which new antitussive medications can be compared. However there are very few studies which have investigated the antitussive efficacy of codeine using cough associated with upper respiratory tract infection (URTI) and there is little if any evidence to support the antitussive efficacy of codeine in this model. This paper discusses the mechanism of cough in man and describes some clinical investigations on the effects of codeine on cough associated with URTI. The recent clinical investigations do not provide any evidence to support an antitussive action of codeine in the treatment of cough associated with URTI yet there is evidence in the literature which indicates that codeine inhibits fictive cough in animal models and also has antitussive activity against both induced and chronic cough models in man. In order to explain these different effects of codeine on the different models of cough, a hypothesis is put forward that there are two cough pathways in man. A voluntary pathway associated with cough related to URTI which is not affected by codeine, and a reflex pathway associated with induced and chronic cough which is inhibited by codeine.
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PMID:Codeine, cough and upper respiratory infection. 923 66

Codeine is generally accepted as the standard antitussive against which new antitussive medications are compared. This presents a problem because the support for codeine's antitussive activity comes from studies on cough in animals, and chronic and induced cough models in man, whereas antitussives are almost exclusively used for the treatment of cough associated with acute upper respiratory tract infection (URTI). The aims of this study were twofold. Firstly, to study the antitussive efficacy of codeine in cough associated with URTI and, secondly, to validate a sound meter as tool for quantifying cough. The efficacy of codeine was assessed in a double-blind, stratified, placebo-controlled, parallel-group, clinical trial using three different measures of cough: cough sound-pressure levels (CSPLs) measured on a sound meter; subjective scores of cough severity; and cough frequency recorded by means of a microphone connected to an ink-pen recorder. A group of 82 subjects (51 females and 31 males; mean age 23.5 years, range 18-46 years) with cough owing to acute URTI were included in the study. The study took place on two separate study days. On study day 1 cough measurements were made before and 90 min after treatment with a single dose of either 50 mg codeine or matched placebo in capsule form. The same three measures of cough were repeated 2-5 days later (study day 2). On study day 1 a highly significant (P < 0.0001) decrease in all three measures of cough was found after treatment with both placebo and codeine yet there was no significant difference between the treatment groups. A highly significant (P < 0.0001) decrease in the three measures of cough was also found between days 1 and 2. The results demonstrate that codeine is no more effective than placebo in reducing cough associated with acute URTI, as measured by CSPLs, cough frequency or subjective symptom scores. This result might be explained on the basis of two central pathways for cough; a reflex pathway via the brain-stem which is sensitive to codeine and a voluntary pathway via the cortex which is unaffected by codeine. The results also demonstrate that the sound-level meter appears to be a potentially useful investigative tool for the assessment of cough and antitussive efficacy.
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PMID:Assessment of the antitussive efficacy of codeine in cough associated with common cold. 936 18

The present study was conducted to determine the effects of administration of centrally active antitussive drugs on the cough motor pattern. Electromyograms of diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough was produced by mechanical stimulation of the intrathoracic trachea. Centrally acting drugs administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral artery administration of all drugs reduced cough number (number of coughs per stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner. Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses that inhibited cough number by 80-90%. Morphine lengthened CTtot and inhibited diaphragm amplitude during cough, but these effects were not dose dependent. Only CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs primarily suppress cough by inhibition of expiratory motor drive and cough number. CTtot and inspiratory motor drive are relatively insensitive to the effects of these drugs. CTtot can be controlled independently from cough number.
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PMID:Influence of central antitussive drugs on the cough motor pattern. 1006 18

Adverse reactions in infants from maternal drug ingestion depend largely on the amount of milk consumed by the infant, timing of breastfeeding in relation to dosing, dose of the medication, dosing interval, and duration of therapy. When taking medications, breastfeeding mothers should be instructed to take their medication after breastfeeding, at the lowest effective dose and for the shortest duration. Overall, there are few data from human studies on the use of antihistamines, decongestants, and cough products during breastfeeding. Studies of pseudoephedrine, triprolidine, and loratadine in humans conclude that low levels of each drug would reach a breastfed infant. Since triprolidine and pseudoephedrine are also considered compatible with breastfeeding by the AAP, these 2 drugs should be the first-line choices. Codeine is considered compatible with breastfeeding by the AAP, and would be an acceptable choice for short-term use as a cough suppressant. It is important to note that many of the liquid cough and cold products contain alcohol. In addition, many of the combination products are a mixture of an antihistamine and a decongestant and may also contain aspirin, acetaminophen, ibuprofen, or caffeine. It is preferable for nursing mothers to only take medications that are necessary and to avoid such combination products. The AAP considers alcohol, acetaminophen, ibuprofen, and caffeine compatible with breastfeeding. Aspirin has been associated with significant negative effects on some nursing infants, and the AAP recommends giving aspirin to nursing mothers with caution. Mothers taking cough and cold products should watch for adverse events in their breastfed infants. Infants may experience paradoxical central nervous stimulation from antihistamines and irritability and insomnia from decongestants.
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PMID:Use of cough and cold preparations during breastfeeding. 1115 4

Cough is an important defensive pulmonary reflex that removes irritants, fluids or foreign materials from the airways. However, often cough is non-productive and requires suppression. Opioid mu receptor agonists, such as codeine are commonly used as antitussive agents and are among the most widely administered drugs in the world. Codeine suppresses the responsiveness of one or more components of the central reflex pathway for cough and is an efficacious antitussive drug for cough due to diverse aetiologies. However, opioids produce side effects that include sedation, addiction potential and constipation. Therefore, novel cough suppressant therapies should maintain or improve upon the antitussive efficacy profile of opioids. Moreover, these novel therapies should have a safety profile significantly better than current antitussive therapies. Presently, we discuss preclinical findings showing that activation of the 'opioid-like' receptor (NOP(1)) inhibits cough in the guinea pig and cat.
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PMID:Antitussive effect of nociceptin/orphanin FQ in experimental cough models. 1209 67

Although effects of antitussive drugs have been examined in inbred small animals using a whole body plethysmography, neuronal mechanisms underlying the cough reflex are not fully understood. The present study analyzed the reflex discharge patterns of the phrenic (PN) and iliohypogastric nerves (IHN) evoked in decerebrate and paralyzed guinea pigs and rats. In guinea pigs, electrical stimulation of the superior laryngeal nerve, chemical stimulation with capsaicin and mechanical stimulation to the intratracheal mucosa equally produced a serial PN-IHN response. This response was characterized by an increased PN discharge and following spindle-shaped burst of the IHN. The evoked discharges overlapped for 20 ms. In rats, by contrast, mechanical stimulation was without effect while capsaicin and electrical stimulation produced two types of responses, both of which differed from that observed in guinea pigs. The first type consisted of an augmented burst of the IHN that was immediately followed by an increased PN discharge. The second type was a large spindle-shaped burst of the IHN that occurred 80 ms after the end of the preceding PN discharge. Codeine (3 mg/kg i.v.) depressed all types of responses evoked in guinea pigs and rats. The present study demonstrated that the fictive cough comparable with those induced in other experimental animals was produced consistently in guinea pigs, but not in rats. Therefore, guinea pigs are suitable for investigation of the neuronal mechanisms underlying the cough reflex and assessment of antitussive drugs.
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PMID:Phrenic and iliohypogastric nerve discharges during tussigenic stimulation in paralyzed and decerebrate guinea pigs and rats. 1532 39

Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.
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PMID:Codeine intoxication associated with ultrarapid CYP2D6 metabolism. 1562 40


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