Effects of flutropium on experimental models of drug- and allergy-induced rhinitis in guinea pigs. (41/216)

The effects of flutropium on histamine (Hist)-induced increase in intranasal pressure in non-sensitized guinea pigs and nasal mucosa capillary permeability in passively sensitized guinea pigs were investigated. Flutropium (0.3%), atropine (0.3%), diphenhydramine (0.01%) and cimetidine (0.1%) were directly inhaled into the nasal cavities by an ultrasonic nebulizer for 20 min, followed by inhalation of Hist (0.1%) for 10 min. Flutropium, atropine and diphenhydramine had an inhibitory action on the Hist-induced increase in intranasal pressure in guinea pigs. Cimetidine had no effect on this system. In passively sensitized guinea pigs (the challenge was performed 48 hr after sensitization), a 0.1-1.0 mg/kg injection of flutropium (i.v.) dose-dependently inhibited the allergic nasal mucosa capillary permeability. Atropine (10 mg/kg, i.v.) had no inhibitory action on this system. These results suggest that inhalation into the nasal cavities and i.v. injection of flutropium are effective in experimental models of drug- and allergy-induced rhinitis of the guinea pig.  (+info)

Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. (42/216)

Diphenhydramine is widely used as an over-the-counter antihistamine. However, the specific human cytochrome P450 (P450) isozymes that mediate the metabolism of diphenhydramine in the range of clinically relevant concentrations (0.14-0.77 microM) remain unclear. Therefore, P450 isozymes involved in N-demethylation, a main metabolic pathway of diphenhydramine, were identified by a liquid chromatography-mass spectrometry method developed in our laboratory. Among 14 recombinant P450 isozymes, CYP2D6 showed the highest activity of diphenhydramine N-demethylation (0.69 pmol/min/pmol P450) at 0.5 microM. CYP2D6 catalyzed diphenhydramine N-demethylation as a high-affinity P450 isozyme, the K(m) value of which was 1.12 +/- 0.21 microM. In addition, CYP1A2, CYP2C9, and CYP2C19 were identified as low-affinity components. In human liver microsomes, involvement of CYP2D6, CYP1A2, CYP2C9, and CYP2C19 in diphenhydramine N-demethylation was confirmed by using P450 isozyme-specific inhibitors. In addition, contributions of these P450 isozymes estimated by the relative activity factor were in good agreement with the results of inhibition studies. Although an inhibitory effect of diphenhydramine on the metabolic activity of CYP2D6 has been reported previously, the results of the present study suggest that it is not only a potent inhibitor but also a high-affinity substrate of CYP2D6. Therefore, it is worth mentioning that the sedative effect of diphenhydramine might be caused by coadministration of CYP2D6 substrate(s)/inhibitor(s). In addition, large differences in the metabolic activities of CYP2D6 and those of CYP1A2, CYP2C9, and CYP2C19 could cause the individual differences in anti-allergic efficacy and the sedative effect of diphenhydramine.  (+info)

Molecular cloning of a gene encoding the histamine H2 receptor. (43/216)

The H2 subclass of histamine receptors mediates gastric acid secretion, and antagonists for this receptor have proven to be effective therapy for acid peptic disorders of the gastrointestinal tract. The physiological action of histamine has been shown to be mediated via a guanine nucleotide-binding protein linked to adenylate cyclase activation and cellular cAMP generation. We capitalized on the technique of polymerase chain reaction, using degenerate oligonucleotide primers based on the known homology between cellular receptors linked to guanine nucleotide-binding proteins to obtain a partial-length clone from canine gastric parietal cell cDNA. This clone was used to obtain a full-length receptor gene from a canine genomic library. Histamine increased in a dose-dependent manner cellular cAMP content in L cells permanently transfected with this gene, and preincubation of the cells with the H2-selective antagonist cimetidine shifted the dose-response curve to the right. Cimetidine inhibited the binding of the radiolabeled H2 receptor-selective ligand [methyl-3H]tiotidine to the transfected cells in a dose-dependent fashion, but the H1-selective antagonist diphenhydramine did not. These data indicate that we have cloned a gene that encodes the H2 subclass of histamine receptors.  (+info)

The use of sleep aids among Emergency Medicine residents: a web based survey. (44/216)

BACKGROUND: Sleepiness is a significant problem among residents due to chronic sleep deprivation. Recent studies have highlighted medical errors due to resident sleep deprivation. We hypothesized residents routinely use pharmacologic sleep aids to manage their sleep deprivation and reduce sleepiness. METHODS: A web-based survey of US allopathic Emergency Medicine (EM) residents was conducted during September 2004. All EM residency program directors were asked to invite their residents to participate. E-mail with reminders was used to solicit participation. Direct questions about use of alcohol and medications to facilitate sleep, and questions requesting details of sleep aids were included. RESULTS: Of 3,971 EM residents, 602 (16%) replied to the survey. Respondents were 71% male, 78% white, and mean (SD) age was 30 (4) years, which is similar to the entire EM resident population reported by the ACGME. There were 32% 1st year, 32% 2nd year, 28% 3rd year, and 8% 4th year residents. The Epworth Sleepiness Scale (ESS) showed 38% of residents were excessively sleepy (ESS 11-16) and 7% were severely sleepy (ESS>16). 46% (95 CI 42%-50%) regularly used alcohol, antihistamines, sleep adjuncts, benzodiazepines, or muscle relaxants to help them fall or stay asleep. Study limitations include low response and self-report. CONCLUSION: Even with a low response rate, sleep aid use among EM residents may be common. How this affects performance, well-being, and health remains unknown.  (+info)

Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice? (45/216)

Febrile nonhemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective therapies for fever and allergy, respectively, so their use in transfusion has some biologic rationale. However, these medications also have potential toxicity, particularly in ill patients, and in the studies performed to date, they have failed to prevent transfusion reactions. Whether the benefits of routine prophylaxis with acetaminophen and diphenhydramine outweigh their risks and cost requires reexamination, particularly in light of the low reaction rates reported at many institutions even when premedication is not prescribed.  (+info)

Self-administration of cocaine-antihistamine combinations: super-additive reinforcing effects. (46/216)

Histamine H1 receptor antagonists have some behavioral effects that predict abuse liability. In the present study, diphenhydramine and cocaine each maintained i.v. self-administration under a progressive-ratio schedule in rhesus monkeys. When cocaine and DPH were combined in a 1:1 ratio of the ED50s, the combination was super-additive in all monkeys. The data predict that the combination of cocaine and histamine H1 receptor antagonists would have enhanced potential for abuse relative to either drug alone.  (+info)

Exposure to alcohol-containing medications during pregnancy. (47/216)

QUESTION: A pregnant patient consulted her physician after discovering that a diphenhydramine preparation (Benadryl elixir) she used for allergy symptoms during the first trimester of her pregnancy contained 15% alcohol. Should she be concerned about fetal alcohol spectrum disorder in her baby? ANSWER: Most ethanol-containing medical preparations are safe during pregnancy. Adult doses of some elixirs with high ethanol concentrations might produce blood levels similar to those achieved by drinking 1 alcoholic beverage. Caution is advisable when prescribing ethanol-containing elixirs to pregnant women, as is informing them about the alcohol content.  (+info)

Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. (48/216)

The present study was undertaken to investigate the effects of some H(1)-antagonists on the sleep-wake cycle in sleep-disturbed rats in comparison with those of nitrazepam. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscle of rats for the electroencephalogram (EEG) and electromyogram (EMG), respectively. EEG and EMG were recorded with an electroencephalograph. SleepSign ver. 2.0 was used for EEG and EMG analysis. The total times of waking, non-rapid eye movement (non-REM), and rapid eye movement (REM) sleep were measured from 10:00 to 16:00. Nitrazepam showed a significant decrease in sleep latency, total waking time, and delta activity and an increase in the total non-REM sleep time. A significant decrease in the sleep latency was observed with diphenhydramine, chlorpheniramine, and cyproheptadine. Cyproheptadine also caused a significant decrease in the total waking time and increases in total non-REM sleep time, REM sleep time, slow wave sleep, and delta activity, although no remarkable effects were observed with diphenhydramine and chlorpheniramine. In conclusion, cyproheptadine can be useful as a hypnotic, having not only sleep inducing-effects, but also sleep quantity- and quality-increasing effects.  (+info)