Antihistamine

Antihistamines are used for reasons ranging from sedation to the treatment of parkinsonism. One of the most common applications of antihistamines, however, is the treatment of the respiratory allergic response to seasonal allergies (hay fever, and so forth) and other allergens (hence their inclusion in this chapter).44,46,64 

Histamine is an endogenous chemical that is involved in the normal regulation of certain physiologic functions (gastric secretion, CNS neural modulation), as well as various hypersensitivity (allergic) 

Generic Name Benzonatate Trade Name(s) Tessalon Method of Action Local anesthetic effect on respiratory mucosa 

Codeine Many trade names Inhibits cough reflex by direct effect on brainstem cough center 

Antihistamines are sold under such trade names as Dimetapp , Actifed , and Benadryl . They have a structure including the group R-X-C-C-N=, where X can be nitrogen, oxygen, or carbon (Fig. 1). 

Antihistamines are produced by certain key steps, such as the synthesis of diphenhydramine from diphenylmethane (Fig. 2). 

Antihistamines are used to alleviate allergic conditions such as rashes and runny eyes and nose and are decongestants that are used for swelled sinuses and nasal passages during the common cold. These symptoms are caused by histamine and hence the drugs that get rid of them are antihistamines. Antihistamines are also sleep inducers. 

The antihistamines synopen and ephedrine were separated and eluted in 10 min on a diol column (A = 254 nm) using a 30/70 methanol/water (10 mM triethylamine to pH 4 with H3PO4) mobile phase. For the most reproducible results the authors correctly noted that the pH of the solution should be monitored in the aqueous phase and then added to the organic. An extensive table of the effects of changing triethylamine concentration, pH, and percent methanol on the retention of the analytes is also presented [545]. 

Ranitidine, ranitidine iV-oxide, ranitidine 5-oxide, and desmethylranitidine were baseline resolved in 8 min on a 40°C Cjg column using a 46/5/49 metha-nol/acetonitrile/water (35 mM phosphate buffer at pH 7.0) mobile phase [546]. Often, as in this case, small amounts of acetonitrile added to the mobile phase will yield sharper peaks and, therefore, overall better efficiency. Here, excellent peak shapes were obtained and responses were linear between 10 and lOOOng. 

Methapyrilene, methapyrilene iV-oxide, and mono-7V-desmethyl methapyrilene were extracted firam urine and baseline resolved on a C,g column (A = 254 nm) using a 40-min 10/90 r- 100/0 methanol/water (lOmM phosphate buffer with 200pL/L triethylamine to pH 7.0) gradient [547]. Extrapolation from the absorb- 

Although sedative antihistamines do not potentiate the effect of alcohol, they should be avoided in excess quantity. Overdose of astemizole can be treated with gastric lavage and supportive measures.86 Coadministration of astemizole and ter-fenadine with antiarrhythmics, antipsychotics, cisapride, and diuretics should be avoided. Chlorpheniramine maleate has been found to be incompatible with phe-nobarbitone sodium, kanamycin sulfate, and calcium chloride. Cyclizines have been used alone or with opioids in tablets or in injectable form for euphoric effects. Cyproheptadine has shown dependence in long-term use. Diphenhydramine is reported to be incompatible with amphotericin, cephalothin sodium, and hydrocortisone sodium succinate. Diphenhydramine and pheniramine maleate are sometimes used as drugs of abuse. Studies have shown that promethazine is adsorbed onto glass, plastic containers, and infusion systems.87 

Diphenhydramine is consumed as well as doxylamine to a small extent. Both substances are also found as intensifiers in plant-derived hypnotic drugs used in self-medication. Sedative antihistamines are regularly consumed by alcoholics and medicament-dependent people over long periods. The dependence of most patients does not tend to attract clinical attention. 

Like the phenothiazine derivatives, substances with antihistamine activity have been separated largely by adsorption chromatography on silica gel layers [6, 35, 52, 145] (cf. Tables 100,101). Silica gel layers that had been prepared with 0.1 N sodium hydroxide, have been used in one instance [52]. Awe and Schulze [6,145] have used a systematic analysis procedure with several solvents for antihistamines also. 

Antazoline, myostimin,e keithon, mebhydroline, captodiamine, orphenadrine, clemizole and buclizine, for example, can be separated by using conditions D in Table 100. Under conditions F, antazoline, brompheniramine, mepyramine, diphenhydramine, chlorphenoxamine, pyrrobutamine, mebhydroline, histapyr-rodine, phenindamine, hydroxyzine, captoindamine, clemizole and buclizine, etc., can be separated. 

Analeptics, Psychotherapeutic Agents with Antidepressive Activity, Appetite Depressants and Some Carbamate Esters of 

The possibility of separation by TLC and the detection of some classical analeptics may be seen in Table 103 and Fig. 162 [63]. 

Most of the monoaminoxidase inhibitors with antidepressive function, listed in Table 104, are hydrazine derivatives and can be separated by TLC on sihca gel layers, using the basic solvents quoted, and detected 

HPI AL is a 23-year-old woman with no medical conditions, who comes into the dink requesting medication for hay fever. She has been experiencing frequent sneezing, watery itchy eyes, and congestion. She works at a law firm during the day and would prefer a quick-acting agent that does not cause sedation. 

Histamine is an endogenous substance that activates histamine H2, and H3 receptors, and its principal pharmacologic effects involve exocrine glands, extravascular smooth muscles, and the cardiovascular system. H, receptor stimulation increases inositol-1,4,5-triphosphate, which increases intracellular calcium, resulting in vasoconstriction. Activation of H2 receptors increases intracellular cAMP, which mediates gastric acid secretions and cardiovascular effects. H3 receptor stimulation may be involved in feedback inhibition of histamine synthesis and release. 

In allergic conditions, histamine released from mast cells, basophils, and other cells bind to and activate specific H, receptors in the nose, eyes, respiratory tract, and skin, causing characteristic symptoms of edema, wheal and flare reactions, itching, rhinorrhea, and lacrimation. Histamine also stimulates nerve endings, causing pruritus. The action of histamine on H, receptors in the microcirculation 

Muscarinic effects, mediated by acetylcholine, the primary transmitter of the autonomic nervous system ganglia, are inhibited by the anticholinergic effects exerted by antihistamines. Anticholinergic side effects include dry mouth, urinary retention, blurred vision, and constipation. Because first-generation antihistamines also distribute into the CNS, sedation is a prominent side effect. The development of second-generation antihistamines, such as loratadine and fexofenadine, lack anticholinergic activity and do not distribute into the CNS (Table 31-1). Hence, they are not typically associated with sedation and do not possess antiemetic properties. 

Case Conclusion AL is prescribed loratadine, a nonsedating antihistamine, to be taken once daily. She is advised not to use it on an as-needed basis but to take it daily to effectively prevent symptoms. 

In the living organism, histamine is synthesized from the naturally occmring a-amino acid, histidine, by the loss of a carboxyl group through bacterial or enzymatic decarboxylation as stated below  

Best et al. (1927) made an epoeh making observation that histamine was present in relatively high coneentration in the lungs, whieh eventually gave rise to vasoconstrietion, anaphylactic shock-like syndrome and acute respiratoiy distress in laboratoiy animals treated with IV administration. Subsequently, the histamine s specific role in the particular pathogenesis of the ensuing anaphylactic reaction was duly demonstrated and substantially established. 

Antihistaminics are widely used in the palliative treatment in allergic conditions like hay fever, urticaria, some forms of pruritus, rhinitis, conjunctivitis, nasal discharge, mild asthma etc. A few antihistaminics possess potent antiemetic action and hence are frequently employed in the prevention and treatment of irradiation sickness, motion sickness (air, sea, road), nausea in pregnancy and postoperative vomiting. 

In general, the most common side-effect of antihistaminics is sedation which may be followed by drowsiness, impaired alertness and retarded ability to perform jobs which need high precision and concentration. 

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Histamine is responsible for many of the symptoms associated with hay fever and other allergies An antihistamine relieves these symptoms by blocking the action of histamine... 

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). 

This compound has antihistaminic activity and is usehil in the therapy of motion sickness. It may also be effective in the control of post-operative nausea and vomiting. It is classified as FDA Category B for Pregnancy, ie, no demonstrated risks shown in animal studies however, no controlled trials in pregnant women. Large doses may cause drowsiness and dry mouth owing to decreased secretion of saUva. 

The history of histamine [51-45-6] (1), and the development of antihistamines have been reviewed (1,2). Histamine was the first to be... 

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

Hj Antihistamine Treatment in Allergic Diseases. H -receptor antagonists are used for the symptomatic treatment of several allergic... 

Clinically Efficacy. It is evident from the mechanism of action of antihistamines and the etiology of allergic diseases that antihistamines in no sense achieve a cure of the patient s allergy. After the adrninistration of a therapeutic dose, a temporal blockade of the effects of histamine is obtained. Whereas classical antihistamines needed at least twice daily adrninistration, for most of the more recently introduced agents adrninistration once daily is sufficient. 

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. 

Topical Application. Azelastine (11) and levocabastine (13) have been developed for topical appHcation (45). The topical antihistamines address the preference of some patients for a local treatment and allow adrninistration of dmg directly to the site requited. The advantage of this therapeutic approach is likely to be in the speed of onset of symptom rehef. In contrast to earlier reports of sensitization with older antihistamines locally apphed to the skin (46), sensitization has not been reported with local appHcation to the nose or eyes. 

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). 

Another large-volume use for organ olithium compounds is in the synthesis of pharmaceutical and agricultural chemicals, eg, antibiotics (qv), antihistamines, antidepressants, anticoagulants, vasodilators, tranquiU2ers, analgesics, fungicides, and pesticides (116—119). 

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. 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

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