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Indian Journal of Dermatology May 2013H1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than...
H1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H1-receptors which are members of the G-protein family. The older first generation H1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H1-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.
PubMed: 23723474
DOI: 10.4103/0019-5154.110832 -
International Journal of Molecular... Jan 2019Antihistamines targeting the histamine H₁ receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more... (Review)
Review
Antihistamines targeting the histamine H₁ receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H₁ receptor occupancy (H₁RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20⁻50%), and sedating (≥50%) groups based on H₁RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H₁RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H₁ receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.
Topics: Animals; Brain; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Receptors, Histamine; Rhinitis, Allergic
PubMed: 30626077
DOI: 10.3390/ijms20010213 -
British Journal of Pharmacology Oct 2009Membrane transporters are now recognized as important determinants of the transmembrane passage of drugs. Organic anion transporting polypeptides (OATP) form a family of... (Review)
Review
Membrane transporters are now recognized as important determinants of the transmembrane passage of drugs. Organic anion transporting polypeptides (OATP) form a family of influx transporters expressed in various tissues important for pharmacokinetics. Of the 11 human OATP transporters, OATP1B1, OATP1B3 and OATP2B1 are expressed on the sinusoidal membrane of hepatocytes and can facilitate the liver uptake of their substrate drugs. OATP1A2 is expressed on the luminal membrane of small intestinal enterocytes and at the blood-brain barrier, potentially mediating drug transport at these sites. Several clinically used drugs have been identified as substrates of OATP transporters (e.g. many statins are substrates of OATP1B1). Some drugs may inhibit OATP transporters (e.g. cyclosporine) causing pharmacokinetic drug-drug interactions. Moreover, genetic variability in genes encoding OATP transporters can result in marked inter-individual differences in pharmacokinetics. For example, a single nucleotide polymorphism (c.521T > C, p.Val174Ala) in the SLCO1B1 gene encoding OATP1B1 decreases the ability of OATP1B1 to transport active simvastatin acid from portal circulation into the liver, resulting in markedly increased plasma concentrations of simvastatin acid and an enhanced risk of simvastatin-induced myopathy. SLCO1B1 polymorphism also affects the pharmacokinetics of many other, but not all (fluvastatin), statins and that of the antidiabetic drug repaglinide, the antihistamine fexofenadine and the endothelin A receptor antagonist atrasentan. This review compiles the current knowledge about the expression and function of human OATP transporters, their substrate and inhibitor specificities, as well as pharmacogenetics.
Topics: Blood-Brain Barrier; Drug Interactions; Genetic Variation; Humans; Intestinal Absorption; Liver; Liver-Specific Organic Anion Transporter 1; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Peptides; Pharmaceutical Preparations; Pharmacogenetics; Pharmacokinetics; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 19785645
DOI: 10.1111/j.1476-5381.2009.00430.x -
Journal of Food and Drug Analysis Apr 2018This review addressed drug interactions precipitated by fruit juices other than grapefruit juice based on randomized controlled trials (RCTs). Literature was identified... (Review)
Review
This review addressed drug interactions precipitated by fruit juices other than grapefruit juice based on randomized controlled trials (RCTs). Literature was identified by searching PubMed, Cochrane Library, Scopus and Web of Science till December 30 2017. Among 46 finally included RCTs, six RCTs simply addressed pharmacodynamic interactions and 33 RCTs studied pharmacokinetic interactions, whereas seven RCTs investigated both pharmacokinetic and pharmacodynamic interactions. Twenty-two juice-drug combinations showed potential clinical relevance. The beneficial combinations included orange juice-ferrous fumarate, lemon juice-Tc-tetrofosmin, pomegranate juice-intravenous iron during hemodialysis, cranberry juice-triple therapy medications for H. pylori, blueberry juice-etanercept, lime juice-antimalarials, and wheat grass juice-chemotherapy. The potential adverse interactions included decreased drug bioavailability (apple juice-fexofenadine, atenolol, aliskiren; orange juice-aliskiren, atenolol, celiprolol, montelukast, fluoroquinolones, alendronate; pomelo juice-sildenafil; grape juice-cyclosporine), increased bioavailability (Seville orange juice-felodipine, pomelo juice-cyclosporine, orange-aluminum containing antacids). Unlike furanocoumarin-rich grapefruit juice which could primarily precipitate drug interactions by strong inhibition of cytochrome P450 3A4 isoenzyme and P-glycoprotein and thus cause deadly outcomes due to co-ingestion with some medications, other fruit juices did not precipitate severely detrimental food-drug interaction despite of sporadic case reports. The extent of a juice-drug interaction may be associated with volume of drinking juice, fruit varieties, type of fruit, time between juice drinking and drug intake, genetic polymorphism in the enzymes or transporters and anthropometric variables. Pharmacists and health professionals should properly screen for and educate patients about potential adverse juice-drug interactions and help minimize their occurrence. Much attention should be paid to adolescents and the elderly who ingest medications with drinking fruit juices or consume fresh fruits during drug treatment. Meanwhile, more researches in this interesting issue should be conducted.
Topics: Citrus paradisi; Cytochrome P-450 CYP3A; Food-Drug Interactions; Fruit and Vegetable Juices; Humans; Randomized Controlled Trials as Topic
PubMed: 29703387
DOI: 10.1016/j.jfda.2018.01.009 -
The Journal of Clinical and Aesthetic... Mar 2023Oral second-generation antihistamines (sgAH) constitute the first-line treatment for chronic spontaneous urticaria (CSU), a debilitating dermatological condition.... (Review)
Review
BACKGROUND
Oral second-generation antihistamines (sgAH) constitute the first-line treatment for chronic spontaneous urticaria (CSU), a debilitating dermatological condition. However, many patients respond incompletely, and up-dosing sgAHs up to four-fold their conventional dose is recommended for disease control. Many physicians refrain from up-dosing due to a paucity of efficacy and safety data, instead adding a second antihistamine or an immunomodulator.
OBJECTIVE
With the aim of addressing this knowledge gap, we conducted a literature review to highlight efficacy and safety data on up-dosed sgAHs.
METHODS
We conducted a comprehensive search of the literature across multiple databases (PubMed, EMBASE, MEDLINE and Google scholar) using the keywords (alone and in combination) and MeSH items as well as non-MeSH terms such as "chronic spontaneous urticaria", "chronic idiopathic urticaria", AND "updosing", "second-generation anti-histamines", "cetirizine", "fexofenadine", "levocetirizine", "desloratadine", "ebastine", "bilastine", and "rupatadine".
RESULTS
Our review suggests bilastine, fexofenadine, levocetirizine, and cetirizine are recommended for up-dosing in non-responsive patients with CSU (Grade A recommendation), while desloratadine and ebastine can be recommended (Grade B recommendation). Among those with Grade A recommendation, bilastine and levocetirizine may be up-dosed safely to four times, while fexofenadine has been studied at three times the conventional dose. None of the drugs showed any dose-dependent increase of adverse effects; however, cetirizine up-dosing may increase the risk of dose-related sedation. There were no reports of systemic complications, including cardiotoxicity, at higher than licensed doses of these drugs. Only cetirizine and rupatadine up-dosing have been documented to be effective and safe in children, while there is lack of data on geriatric patients and pregnant or lactating females.
PubMed: 36950042
DOI: No ID Found -
Therapeutics and Clinical Risk... 2016Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation... (Review)
Review
Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug-drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug's safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria.
PubMed: 27110120
DOI: 10.2147/TCRM.S105189 -
Indian Journal of Pharmacology 2016Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial.
OBJECTIVES
Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR.
MATERIALS AND METHODS
Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18-65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter.
RESULTS
Evaluation of TNSS revealed significant difference ( < 0.05) when compared from baseline to 4 week in both groups. The mean change of TNSS, i.e., 9.46 was significant ( < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group.
CONCLUSION
The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.
Topics: Acetates; Anti-Allergic Agents; Anti-Asthmatic Agents; Cetirizine; Cost-Benefit Analysis; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Quinolines; Rhinitis, Allergic; Sulfides; Terfenadine; Treatment Outcome
PubMed: 28066101
DOI: 10.4103/0253-7613.194854