Fexofenadine Allegra

Antihistamines are drags used to counteract the effects of histamine on body organs and structures. Examples of antihistamines include diphenhydramine (Benadryl), loratadine (Claritin), fexofenadine (Allegra), and cetirizine (Zyrtec). A new antihistamine, deslorata-dine (Clarinex), is die active metabolite of loratadine and is intended to eventually replace loratadine (Claritin). Topical corticosteroid nasal sprays such as fluticasone propionate (Flonase) or triamcinolone ace-tonide (Nasacort AQ) are also used for nasal allergy symptoms. See Chapter 56 for more information on die topical corticosteroids. 

Fexofenadine (Allegra) Antihistamine Filgrastim Leukocyte-stimulat-... 

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 It has been replaced by its safer but no less effective carboxylic oxidative metabolite fexofenadine (Allegra). 

Sometimes an active pharmaceutical produces another active agent after biotransformation. An example of a commercially popular drug with an active metabolite is terfenadine (Seldane )/ as shown in Scheme 11.3. As discussed in Chapter 1/ the terfenadine oxidative metabolite/ fexofenadine (Allegra )/ is now marketed as a safer alternative that avoids potentially fatal cardiac terfenadine side effects. 

There is stunning similarity between the penclomedine story and the history of terfenadine (Seldane), a highly successful antihistamine product that was withdrawn from marketing. In early clinical studies of terfenadines, it was not appreciated that the major source of clinical benefit was its metabolite, fexofenadine (Allegra see structures in Chapter 1, Figure 1.2). It became obvious that the metabolite should have been the lead compound only after car-diotoxicity was subsequently discovered for the parent drug but not the metabolite. 

The primary metabolite of terfanidine (/ =OH) was recently (1996) marketed as fexofenadine (Allegra). It may not exhibit the serious drug interactions with ketoconazole and erythromycins. 

Figure 19.19 Compounds related to the antihistamine arena. Compound 41, diphenhydramine (Benadryl ) is an older antihistamine that exhibits considerable sedating side-effects. Analogs 42 to 44 (fexofenadine (Allegra ), loratadine (Claritin ), cetirizine (Zyrtec ), respectively) are newer, nonsedating antihistamines. Many of the newer agents are now thought to be good substrates for P-glycoprotein (Pgp), which is situated within the BBB and serves to pump drugs out of the CNS and into the cerebral circulation (brain capillaries).

Fexofenadine Allegra Hoechst-Marion-Roussel R Non-sedating antihistamine... 

Which client should the nurse question administering the Hj receptor antagonist fexofenadine (Allegra) ... 

Active metabolites may have superior pharmacological, pharmacokinetic, and safety profiles compared to their respective parent molecules (Fura, 2006 Fura et al., 2004). As a result, a number of active metabolites have been developed and marketed as drugs with improved profiles relative to their parent molecules. Examples of active metabolites of marketed drugs that have been developed as drugs include acetaminophen, oxyphenbutazone, oxazepam, cetirizine (Zyrtec), fexofenadine (Allegra), and desloratadine (Clarinex). Each of these drugs provides a spedlic benefit over the parent molecule and is superior in one or more of the categories described above. 

Label all stereocenters in loratadine (Claritin ) and fexofenadine (Allegra ), now the top-selling antihistamines in the United States. Tell how many stereoisomers are possible for each. (See Examples 6.5, 6.6)... 

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