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)

Loratadine is a new selective peripheral histamine H1-receptor antagonist, that is orally effective, long-acting, and devoid of significant central and autonomic nervous system activity. Its safety and efficacy were evaluated in a 28-day study conducted in patients with chronic idiopathic urticaria. Patients were randomly assigned to one of three treatment groups (loratadine, 10 mg OD; terfenadine, 60 mg BID; or placebo). Evaluation of efficacy included weekly assessments of the individual disease signs and symptoms, the overall disease condition, and therapeutic response to treatment. Throughout the 28-day treatment period progressive improvement was observed in the loratadine and terfenadine treatment groups; however, at each evaluation, loratadine was significantly more effective than placebo (P less than .01) and clinically more effective than terfenadine in reducing disease signs and symptoms. Terfenadine was significantly more effective than placebo at day 7 and endpoint (last valid visit). The overall therapeutic response at the endpoint of treatment was rated as marked or complete relief of symptoms in 64%, 52%, and 25% of the patients in the loratadine, terfenadine, and placebo treatment groups, respectively. Loratadine was well tolerated and comparable to terfenadine and placebo in incidence of adverse experiences. Sedation was reported in one patient each in the terfenadine and placebo treatment groups and an anticholinergic side effect (dry mouth) in one terfenadine-treated patient. No sedative or anticholinergic side effects were observed in patients receiving loratadine. We concluded that loratadine, 10 mg, once daily is a safe and effective treatment for symptomatic relief of chronic idiopathic urticaria.
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PMID:Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. 196 19

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating histamine H1-receptor antagonists terfenadine, astemizole, loratadine, and acrivastine are reviewed. Terfenadine and astemizole are chemically unrelated to histamine H1-receptor antagonists such as diphenhydramine and chlorpheniramine. Loratadine is structurally related to the antihistamine azatadine, and acrivastine is a side-chain-reduced metabolite of the antihistamine triprolidine. Like other histamine H1-receptor antagonists, they competitively block histamine receptor sites rather than inhibiting histamine release. All four drugs have relatively long half-lives and are rapidly absorbed after oral administration. Terfenadine, astemizole, and loratadine are metabolized extensively in the liver; terfenadine and astemizole are both 97% protein bound. Terfenadine 60 mg twice daily has been shown to be as effective as conventional antihistamines for the treatment of seasonal allergic rhinitis. In clinical trials, astemizole 10 mg daily was comparable to or better than chlorpheniramine for treatment of chronic rhinitis. Both terfenadine and astemizole were effective for treatment of chronic urticaria. For treatment of seasonal allergic rhinitis, loratadine combined with pseudoephedrine may be preferable to triprolidine-pseudoephedrine and acrivastine-pseudoephedrine combinations that require more frequent dosing. Acrivastine must be administered more frequently than the other nonsedating antihistamines. None of these four agents impairs psychomotor activity. Infrequently reported adverse effects include dry mouth, skin reactions, and weight gain. The absence of substantial sedative effects and the less-frequent dosing schedules make these agents good alternatives to the classic antihistamines for treatment of seasonal and chronic rhinitis and chronic urticaria.
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PMID:Nonsedating histamine H1-receptor antagonists. 256 12

Newer, nonsedating antihistamines provide a therapeutic alternative for the patient with allergy whose work is impaired by the side effects of traditional H1 antihistamines. To assess the differential effect of these antihistamines on reaction times and subjective symptoms, we compared terfenadine, 60 mg twice daily, to hydroxyzine, 25 mg twice daily, in a double-blind, placebo-controlled, crossover study of 16 healthy, asymptomatic adults. Simple reaction time and choice reaction time were measured with a computer-based, eye-hand, reaction-time testing apparatus. Reaction times and symptom scores were assessed 90 minutes after the fourth and tenth doses of each drug. Hydroxyzine, but not terfenadine, significantly prolonged both simple and choice reaction time (p less than or equal to 0.0001). However, decision time, the time to process one bit of spatial information, was not prolonged by either antihistamine. Therefore, hydroxyzine prolonged the interpretation and response to stimuli of the central nervous system without increasing single-bit processing time. Although terfenadine was not different from placebo for any symptom assessed, hydroxyzine produced significant drowsiness (p = 0.001), dry mouth (p = 0.022), and irritability (p = 0.021). During the 5 days of hydroxyzine administration, neither objective nor subjective symptoms demonstrated the development of tolerance. No correlation was found between subjective symptoms and prolongation of reaction times by hydroxyzine, suggesting that side effect symptoms of traditional antihistamines are unreliable predictors of objective performance. Terfenadine provides a promising therapeutic alternative to traditional antihistamines for individuals performing critical tasks.
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PMID:Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine. 257 Jul 98

Specific H1 antihistamines have become the standard of treatment for relief of symptoms associated with seasonal allergic rhinitis. First-generation antihistamines are small lipophilic molecules that are associated with numerous adverse events largely because of their propensity to cross the blood-brain barrier and their cholinergic activity. Second-generation antihistamines, being more lipophobic, offer the advantages of a lack of CNS and cholinergic effects such as sedation and dry mouth, which are commonly seen in first-generation antihistamines. Their longer duration of action also enables a more patient-friendly dosing regimen which increases patient compliance. This paper reviews the pharmacokinetic properties of these second-generation agents and is intended to provide comparisons that help explain differences in dosing profiles and drug interactions for members of this class of drugs. With the announced withdrawal of terfenadine from the U.S. market in early 1997, 4 second-generation antihistamines are currently widely available: astemizole, loratadine, cetirizine, and fexofenadine. Terfenadine and astemizole both produce significant cardiac QT interval prolongation that may progress to a rare but fatal cardiac ventricular tachycardia known as torsades de pointes. While only terfenadine has been withdrawn due to its adverse effects profile, significant warnings were recently issued for astemizole. The pharmacokinetic profiles of loratadine and cetirizine are reflective of the advantages of these agents as non-cardiotoxic antihistamines. With respect to the newest agent fexofenadine, the major metabolite of terfenadine, published reports are minimal, but its pharmacokinetics differs from that of terfenadine.
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PMID:Pharmacokinetic overview of oral second-generation H1 antihistamines. 1039 24