Antihistamines preparations

Each antihistamine may be used for one or more of these reasons. The more specific uses of the various antihistamine preparations are given in the Summary Drug Table Antihistamines. 

Iatrogenic Reactions broadly refer to any adverse reactions that are unintentionally produced by physicians in their patients. For example, one of the side effects of many antihistaminic preparations (Hj antagonists) such as ethanolamine derivatives (prototype diphenhydramine) is heavy sedation. Although sedation may be desirable for some patients, it may interfere with daytime activities, and this needs to be considered when prescribing such medications. Other antihistaminic preparations (also 11 antagonists) such as piperidine derivatives (prototypes terfenadine or astemizole) have no sedative properties (Figure 3.2). 

Smith HA, Evanson RV, Sperandio GJ. The development of a liquid antihistaminic preparation with sustained release properties. 

Anesthetics, packaged Antacids Anthelmintics Antibiotics, packaged Antihistamine preparations Antipyretics Antiseptics, medicinal Astringents, medicinal Bai bituric and pharmaceutical preparations... 

Azelastine is an ophthalmic antihistaminic preparation. It is indicated in the treatment of symptoms of seasonal allergic rhinitis, such as rhinorrhea, sneezing, and nasal pruritus treatment of symptoms of vasomotor rhinitis, such as rhin-orrhea, nasal congestion, and postnasal drip (nasal inhalation) treatment of itching of eye associated with allergic conjunctivitis (ophthalmic). 

Topical antihistamine preparations are used because they are slightly antipruritic and may have a mild local anesthetic effect. However, such topical antihistamines are common and potent sensitizers. 

Although topical phenothiazine antihistamine preparations such as promethazine hydrochloride (Phenergan) cream are no longer used in the United States, such topical antihistamine preparations are still widely used in Europe. Individuals who have become sensitized by such topical phenothiazine antihistamines often suffer a flare of the dermatitis when a phenothiazine antihistamine is taken, i.e., a systemic eczematous contact dermatitis. In addition, many individuals acquire allergic sensitization to various phenothiazine drugs which show cross-reactions with the phenothiazine antihistamines. Table 6 lists the phenothiazine antihistamine compounds. 

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

Lithium Amide. Lithium amide [7782-89-0], LiNH2, is produced from the reaction of anhydrous ammonia and lithium hydride. The compound can also be prepared by the removal of ammonia from solutions of lithium metal in the presence of catalysts (54). Lithium amide starts to decompose at 320°C and melts at 375°C. Decomposition of the amide above 400°C results first in lithium imide, Li2NH, and eventually in lithium nitride, Li N. Lithium amide is used in the production of antioxidants (qv) and antihistamines (see HiSTAMlNE AND HISTAMINE ANTAGONISTS). 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

Diphenhydramine [58-73-1] (55) was originally developed as an antihistamine and was first used clinically for this purpose in 1946 (see HiSTAMlNE AND HISTAMINE antagonists). In addition to this primary effect, however, central antitussive activity has also been demonstrated in animals (75,76) and in humans (77). Its antitussive activity is about half that of codeine. Drowsiness is the most frequent side effect. Diphenhydramine can be prepared as follows (78) ... 

Benzimidazoles are generally synthesized from ortho-diamino-benzenes and carboxylic acid derivatives. The antihistaminic agent, clemizole (60), for example, can be prepared by first reacting ortho-diaminobenzene (57) with chloroacetic acid to form 2-chloro-methylbenzimidazole (58). Displacement of the halogen with pyro-... 

The parent drug of this series, promazine (24), was prepared originally as an antihistamine. Following the identification of the more potent chloro analog as an antipsychotic, it too came into use for that indication. The drug is prepared by straightforward alkylation of phenothiazine with w-C3-chloropropyl)di-methylamine by means of sodium hydride in xylene. ... 

An intermediate used in the preparation of the antihistamine, propiomazine, serves as starting material for a 2-substi-tuted major tranquilizer as well. Thus, reaction of the phosgene... 

Drowsiness and sedation are common adverse reactions seen with the use of many of the antihistamines. Some antihistamines appear to cause more drowsiness and sedation than others. These dm may also have varying degrees of anticholinergic (cholinergic blocking) effects, which may result in dryness of the mouth, nose, and throat and a thickening of bronchial secretions. Several newer preparations (eg, loratadine) cause little, if any, drowsiness and fewer anticholinergic effects than some of the other antihistamines. Hiotosensitivity may occur with the use of the antihistamines. 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Nowhere, perhaps, is this phenomenon better illustrated than in the phenothiazine class. The earlier volume devoted a full chapter to the discussion of this important structural class, which was represented by both major tranquilizers and antihistamines. The lone phenothiazine below, flutiazin (130), in fact fails to show the activities characteristic of its class. Instead, the ring system is used as the aromatic nucleus for a nonsteroidal antiinflammatory agent. Preparation of 130 starts with formylation of the rather complex aniline 123. Reaction with alcoholic sodium hydroxide results in net overall transformation to the phenothiazine by the Smiles rearrangement. The sequence begins with formation of the anion on the amide nitrogen addition to the carbon bearing sulfur affords the corresponding transient spiro intermediate 126. Rearomatization... 

This approach (Scheme 3) has been applied (53JCS1636) to the synthesis of 4(5)-aminoimidazole derivatives with potential antihistamine or anthelmintic properties. For example, 4(5)-amino-2-thymyloxymethylimidazole (47) was obtained from benzyl-thymyloxy acetothioimidate hydrochloride (42) (75%). Similarly, 4(5)-amino-2-phenylimidazole (48) and 4(5)-amino-2-(thiophen-3-yl)imidazole (49) were prepared (72CA19645) from benzyl-phenyl acetothioimidate hydrochloride (43) and benzyl-(thiophen-3-yl) acetothioimidate hydrochloride (44), respectively. 

For example, a pharmacist was asked to prepare 30-0 ml of a solution of cetirizine hydrochloride (an antihistamine medicine) with a concentration of 5-0 mg/ml. The stock solution of cetirizine hydrochloride was 75-0 mg/ml. Calculate the volume of stock solution needed to prepare the diluted medicine. 

Rhinocort Aqua and Nasonex are preparations containing topical nasal corticosteroids (budesonide and mometasone furoate respectively). Otrivine contains a nasal decongestant (xylometazoline) and Sudafed is a systemic preparation containing a nasal decongestant (phenylephrine). Molcer is a preparation for ear-wax removal and which contains docusate sodium. Emadine contains an antihistamine (emedastine) and is presented as eye drops. 

Nappy rash is effectively managed by the application of a barrier preparation, such as zinc and castor oil ointment. Antihistamine creams such as mepyramine and antipruritic creams such as Eurax cream, containing crotamiton, are of no use. 

Desloratadine is a non-sedating antihistamine. Diphenhydramine, chlor-phenamine, promethazine and alimemazine are sedating antihistamines with diphenhydramine and promethazine being marketed in over-the-counter hypnotic preparations. 

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