Nonsedating antihistamines

Antihistamines, nonsedating/Cisapride/Pimozide- Cisapride and pimozide are metabolized by the cytochrome P-450 3A4 isozyme inhibitors of 3A4 can block the metabolism of these drugs, resulting in increased plasma concentrations of parent drug, which is associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, because of ventricular tachycardia of the torsades de pointes type. In vitro, nefazodone inhibits 3A4. It is recommended that nefazodone not be used in combination with cisapride or pimozide. 

Chemical/Pharmaceutical/Other Class Antihistamine Nonsedating antihistamine H-1 receptor antagonist... 

Nevertheless, although the nonsedating H antihistamines have substantially improved the acceptabiUty and clinical efficacy of this class of compounds, these do not provide complete rehef eye disease responds less well than nasal disease, of the rhinitis symptoms nasal congestion responds poorly, breakthrough symptoms occur at high poUen counts, and only some 70% of patients report excellent to good treatment responses. Considerable research therefore still continues in the H antihistamine field. New antihistamines are continually being introduced. 

The search for nonsedating H-1 antihistamines met its first success in terfenadine (see 198, Chapter 2). A different approach aimed at keeping such agents out of the CNS, by prevent-... 

Yet another nonsedating zwitterionic H-1 antihistamine consists of the product from metabolism of the terminal hydroxyl of the potent antihistamine hydroxyzine terminating in hydroxymethyl instead of a carboxylic acid. This compound, cetirzine (123), can be obtained in straightforward fashion by alkylation of the monosubstituted piperazine 120 with halide 121, via the amide 122 [27]. 

Demethylation of the tricyclic antihistamine 9, with cyanogen bromide gives the secondary amine 10 acylation of that intermediate with ethyl chloroformate affords the nonsedating H-1 antihistaminic agent loratidine (11) [3], It is of interest that this compound does not contain the zwitterionic funcrion which is thought to prevent passage through the blood-brain barrier, characteristic of this class of compounds. 

Yet another related approach to pharmacotherapy management is step protocols or step therapy. Step protocols limit access to certain drugs until less costly alternative drugs have been tried first. For example, a step protocol might require a patient to have tried a relatively low-cost antihistamine, such as chlorpheniramine, before being prescribed a more expensive nonsedating antihistamine. Step therapy procedures were in place at 68.5% of HMOs in 1998 [1]. 

Second-generation nonsedating antihistamines (e.g., loratadine) are not associated with erectile dysfunction. 

N. Yumibe, K. Huie, K. J. Chen, M. Snow, R. P. Clement, M. N. Cayen, Identification of Human Liver Cytochrome P450 Enzymes That Metabobze the Nonsedating Antihistamine Loratadine , Biochem. Pharmacol. 1995, 51, 163- 172. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Coadministration of ritonavir with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse reactions due to possible effects of ritonavir on the hepatic metabolism of certain drugs (see Contraindications). 

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Arrhythmogenic mechanisms of nonsedating antihistamines. Clinical and Experimental Allergy, 29 (Suppl 3), 174-181. 

More potent antihistamine than nonsedating agents (e.j first-line choice for allergic rhinitis... 

Mechanism of Action A nonsedating antihistamine that exhibits selective peripheral histamine Hi-receptor blocking action. Competes with histamine at receptor sites. Therapeutic Effect Prevents allergic responses mediated by histamine, such as rhinitis and urticaria. 

Effective, but expensive nonsedating antihistamine reserve for patients unable to tolerate sedating antihistamines like chlorpheniramine... 

Potential interactions with nonsedating antihistamines, cisapride (cytochrome... 

Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds such as 28 or 29 (Fig. 2.1.3.8). Among several drug candidates, Cetirizine hydrochloride (28) stands out as a commercially important nonsedative antihistamine agent. Binding studies indicate that... 

One can find many more examples where a subtle modification in a side chain leads to a new drug that produces a drastically different therapeutic or toxicological outcome. This is clearly illustrated by the nonsedating antihistamine terfenadine (Seldane), which produces cardiotoxicity when given with certain drugs that inhibits its metabolism. This product is no longer marketed. It has been replaced by its safer but no less effective carboxylic oxidative metabolite fexofenadine (Allegra). 

Occasionally a metabolite may provide a safer or more effective pharmaceutical than the parent compound selected for development. For example, fexofenadine, a widely sold nonsedating antihistamine, is the active metabolite of terfenadine. Fexofenadine is a safer drug than terfenadine and has replaced it on the market. 

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