Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

First-generation antihistamines have potency, pharmacokinetic, and cost advantages compared with nonsedating second-generation antihistamines. Bedtime dosing of hydroxyzine was investigated as a dosing strategy to minimize reaction time degradation and adverse subjective symptoms previously documented for hydroxyzine in divided doses. Hydroxyzine, 50 mg qhs, was compared with terfenadine, 60 mg bid, in this double-blind, placebo-controlled crossover study of 15 healthy, asymptomatic adults. Computer-based eye-hand reaction time tests of simple reaction time (SRT) and choice reaction time (CRT) were not statistically different among the three drugs. Drowsiness, dry mouth, and irritability were significant for hydroxyzine (P = .0001, .001 and .02, respectively) compared with terfenadine or placebo, but less than seen in a previous study of hydroxyzine, 25 mg bid. Symptom scores with terfenadine were comparable to placebo. Histamine skin test wheal and flare were both significantly and comparably suppressed by hydroxyzine and terfenadine (P = .0001). While wheal suppression by hydroxyzine was universal, four of the 15 subjects showed little or no suppression with terfenadine (P = .03). Although bedtime dosing of hydroxyzine did not eliminate subjective symptoms, it maintained skin H1-receptor antagonism the following morning and alleviated the prolongation of reaction times previously reported with hydroxyzine in divided doses. The significant adverse subjective symptoms and psychomotor performance degradations caused by first-generation antihistamines can be mitigated by creative dosing schedules.
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PMID:Objective antihistamine side effects are mitigated by evening dosing of hydroxyzine. 168 92

Hydroxyzine, a potent H1-receptor antagonist often used for relief of pruritus in patients with hepatic dysfunction, was studied in eight patients, mean age 53.4 +/- SD 11.2 years, with primary biliary cirrhosis. The patients ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 43.9 +/- 6.6 mg). Before the dose, then hourly for 6 hours, every 2 hours from 6-12 hours, at 24 hours, and every 24 hours for 6 days, serum hydroxyzine and cetirizine were measured and an intradermal injection of 0.01 mL of a 0.1 mg/mL solution of histamine phosphate was performed. Wheals and flares were traced at 10 minutes and the areas were calculated. Mean peak hydroxyzine levels of 116.5 +/- 60.6 ng/mL occurred at 2.3 +/- 0.7 hours and mean peak cetirizine levels of 500.4 +/- 302.0 ng/mL occurred at 4.8 +/- 2.8 hours. The mean serum elimination half-life of hydroxyzine was 36.6 +/- 13.1 hours, and the mean serum elimination half-life of cetirizine was 25.0 +/- 8.2 hours. The mean hydroxyzine clearance rate was 8.65 +/- 7.46 mL/min/kg, and the mean volume of distribution was 22.7 +/- 13.3 L/kg. The mean wheal area was suppressed (P less than 0.01) from 1 to 120 hours, with maximal suppression from 2 to 48 hours. The mean flare area was suppressed from 1 to 144 hours, with maximal suppression from 3 to 24 hours (P less than 0.01). All patients became sleepy from 0.5 to 6 hours. Blurred vision, dizziness and dry mouth each occurred in two patients. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacokinetics and pharmacodynamics of hydroxyzine in patients with primary biliary cirrhosis. 257 11

Doxepin hydrochloride, a tricyclic antidepressant, was evaluated in a double-blind, placebo-controlled crossover trial for the treatment of chronic idiopathic urticaria in 16 adults. Efficacy was evaluated by symptom scores, concomitant antihistamine use, and suppression of histamine- and codeine-induced wheal response. Doxepin-treated subjects experienced fewer lesions (p less than 0.001), less waking hours with lesions (p less than 0.01), lesser degree of itch and/or discomfort (p less than 0.001), and less swelling or angioedema (p less than 0.001) as compared to placebo-treated subjects. Doxepin-treated subjects required less daily concomitant antihistamine use (mean 0.13 tablets versus 1.48 tablets, p less than 0.05). Doxepin also significantly suppressed histamine- and codeine-induced cutaneous wheal response as compared to placebo. Lethargy was commonly observed but diminished with continued use. Dry mouth and constipation were also commonly observed. We conclude that doxepin is an effective agent for the treatment of chronic idiopathic urticaria.
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PMID:Efficacy of doxepin in the treatment of chronic idiopathic urticaria. 378 54

Ebastine and its active metabolite carebastine show potent antagonism of histamine H1-mediated phenomena in a wide variety of in vitro and in vivo non-clinical experimental models. By contrast, activity is not seen against histamine H2- or H3-mediated, nor acetylcholine- or serotonin-mediated phenomena, and both compounds are virtually without effect in models measuring pharmacological effects on the central nervous system (CNS). Explanation of these observations is found in their high selectivity for the histamine H1 receptor and in their low in vivo potency in displacing [3H]-mepyramine from central histamine H1 receptors, indicating that they do not readily pass the blood-brain barrier. These findings have been mirrored in clinical experimental models where oral doses of ebastine (1-30 mg) showed clear dose-related inhibition of intradermal histamine-induced weal and flare responses, whereas doses of 90 mg were without anticholinergic effects on salivary flow, cardiovascular reflexes or pilocarpine-induced miosis. Furthermore, in an extensive series of controlled studies in specific clinical models for measuring objective effects on the CNS, ebastine in single doses of 10-90 mg and repeated doses of 10-30 mg once daily, had no clinically relevant effects on cognitive performance and visual co-ordination tests, nor on simulated car-tracking tests and real car-driving tests. Nor was their any interaction with ethanol or diazepam. On subjective test parameters (questionnaires and visual analogue scales) there were only a few isolated and random incidences of minor increases in some indices of sedation at the highest doses. Not surprisingly, therefore, the clear therapeutic benefit seen during the extensive and international use of ebastine (5-20 mg once daily) in the treatment of seasonal and perennial rhinitis and chronic idiopathic urticaria, has not been accompanied by signs of drug-induced anticholinergic effects (dry mouth, disturbances of visual accommodation) or sedation, making it an effective and well-tolerated first-line treatment alternative to other second-generation antihistamines.
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PMID:The non-cardiac systemic side-effects of antihistamines: ebastine. 1044 30

Cetirizine hydrochloride is an orally-active and selective histamine (H(1))-receptor antagonist. It is a second-generation antihistamine and a human metabolite of hydroxyzine. Therefore, its principal effects are mediated via selective inhibition of peripheral H(1) receptors. The antihistaminic activity of cetirizine has been documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth has been seen more commonly with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for receptors other than H(1) receptors. Auto-radiographical studies with radiolabelled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H(1) receptors. Impairment of CNS function is comparable to other low-sedating antihistamines at the recommended dose of 10 mg/day for adults. It has anti-inflammatory properties that may play a role in asthma management. It does not interact with concomitantly administered medications, it has no cardiac adverse effects, and it does not appear to be associated with teratogenicity. Cetirizine is predominantly eliminated by the kidneys with a mean elimination half-life is 8.3 h. It is rapidly absorbed, and significant clinical inhibition of a wheal and flare response occurs in infants, children and adults within 20 min of a single oral dose and persists for 24 h. No tolerance to the wheal and flare response occurs even after 1 month of daily treatment. The clinical efficacy of cetirizine for allergic respiratory diseases has been established in numerous trials. There is evidence that cetirizine improves symptoms of urticaria. Concomitant use of cetirizine also decreases the duration and amount of topical anti-inflammatory preparations needed for the treatment of atopic dermatitis. Interestingly, several clinical studies suggest that cetirizine may be useful in the treatment and prevention of mild asthma.
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PMID:Review of cetirizine hydrochloride for the treatment of allergic disorders. 1468 Apr 42

Dexmedetomidine, a sedative administered by continuous infusion, is used to facilitate mechanical ventilation through alpha(2)-receptor activation. The drug's most common adverse reactions include hypotension, hypertension, nausea, bradycardia, and dry mouth. However, to our knowledge, no reports of dermatologic allergic reactions from dexmedetomidine use have been published. We describe a 22-year-old man who was intubated after being injured in a motor vehicle collision. He had been receiving propofol and fentanyl infusions for sedation during mechanical ventilation and was transitioning to dexmedetomidine. Within 4 hours of receiving dexmedetomidine 0.2 microg/kg/hour, the patient developed a wheal-and-flare rash encompassing 60% of his body surface area. The infusion was immediately discontinued; over the next 24 hours most of the rash receded, and within 48 hours of drug discontinuation the rash had completely resolved. According to the Naranjo adverse drug reaction probability scale, the likelihood that this rash was induced by dexmedetomidine was probable. Clinicians should be aware of this potential dermatologic adverse effect from dexmedetomidine, and patients receiving the drug should be closely monitored.
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PMID:Severe rash associated with dexmedetomidine use during mechanical ventilation. 1932 24