Antihistamines receptor antagonist

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

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. 

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

The belief that histamine (HT) has a central effect stems from the knowledge that all the classical antihistamines (Hi receptor antagonists) used to treat allergic reaction, such as hay fever, caused marked sedation if, like mepyramine and promethazine, they can cross the blood-brain barrier, but fail to do so if, like terfenedine and cetirizine, they do not. 

Although histamine has mixed excitatory and inhibitory effects on central neurons, those antihistamines (Hi-receptor antagonists) that enter the brain produce sedation this indicates that the predominant overall effect of histamine is excitatory. The preferred explanation for this rests on evidence that histaminergic neurons in the posterior hypothalamus are active in waking and silent in deep SWS and REM sleep. 

Oral pseudoephedrine should not be used in children under 1 year of age due to safety concerns. Intranasal ipratropium can be used as intermittent therapy for mild rhinitis or as add-on therapy in more severe cases. AIT is recommended for persistent rhinitis, particularly severe disease, because studies have shown that children respond better than adults. Montelukast is indicated for children 2 years of age and older with SAR and for infants 6 months of age and older with PAR. Studies evaluating leukotriene receptor antagonists as monotherapy or in combination with antihistamines have contradictory results.33... 

The hypothesis of the role of HA in wakefulness stems from the observation that administration of the classical antihistamines (i.e. H3 receptor antagonists) induced sedation. These first-generation antihistamines, used to treat inflammatory reactions, could cross the blood-brain barrier and block the central Hi receptor (White Rumbold, 1988). The first study examining the effect of antihistamines on sleep-wakefulness in cats reported an increase in NREM sleep and a decrease in REM sleep (Jewett, 1968). Similar results were also obtained in dogs (Wauquier et ah, 1981) and humans (Risberg et ah, 1975 Bassano Caille, 1979 Nicholson et ah, 1985 Adam Oswald, 1986). Intraventricular application of HA in the anesthetized rat caused a dose-dependent decrease in the duration of narcosis, whereas intraventricular application of HA in conscious... 

Hydroxy or hydroxymethyl groups attached to quinolizine substrates normally show the expected reactivity. For instance, compound 109 was linked to histamine receptor antagonists by esterification with succinic anhydride followed by amidification with the antihistaminic drug to give the fluorescently labeled stmcture 110 for in vivo studies of receptor binding (Scheme 13) <2003BML1717>. 

Montelukast (Singulair) is a leukotriene receptor antagonist approved for treatment of seasonal allergic rhinitis. It is effective alone or in combination with an antihistamine. 

Traditional or Hj antihistamine drugs block many effects caused by histamine however, it turns out that they are not able to withstand events mediated by H2 receptors, in particular excess gastric juice secretion. In 1977 an H2-receptor antagonist, cimetidine, was proposed, which revolutionized stomach ulcer treatment. Later on, ranitidine was proposed, followed by drugs with minor structural and pharmacological differences such as famotidine and nizatidine. 

Antihistamines are reversible, competitive Hi receptor antagonists that reduce or prevent most of the physiologic effects that histamine normally induces at the H- ... 

Histamine Hi receptor antagonists which enter the brain (diphenhydramine, promethazine and others) have sedative actions and polysomnographic recordings have shown that they suppress REM sleep and modestly increase SWS. A rebound in REM sleep sometimes occurs on discontinuation. Stimulation of central Hi and H2 receptors markedly potentiates signals produced by excitatory amino acids and it has been suggested that histamine acts as a waking amine (Schwartz et al., 1986). The effects of centrally acting antihistamines on sleep may be due to inhibition of these effects. 

As first choice treatment a well-established antihistamine such as meclozine is recommended. Promethazine is another antihistamine which reduces nausea, but sedation is a not always desired adverse effect. Metoclopramide increases intestinal motility and could be used short term also early in pregnancy. A neuroleptic such as prochlorperazine reduces nausea but should only be used for shortterm treatment due to the risk of extrapyramidal adverse reactions. Serotonin receptor antagonists can be used in post-operahve nausea and during treatment with cytostatics. 

Hydroxyzine hydrochloride Atarax, Vistarit) is the antihistamine with the greatest use in the treatment of anxiety. It is often used to reduce the anxiety that is associated with anesthesia and surgery. It also produces sedation, dries mucous membranes (via an anticholinergic mechanism), and has antiemetic activity. A more extensive discussion of the pharmacology of the Hj-receptor antagonists is found in Chapter 38. 

Hj receptor antagonists (antihistamines) are among the most widely used therapeutic agents. Indeed, sometimes the exact same molecule (e.g., diphenhydramine) is marketed in different aisles in the same pharmacy under many brand names for different... 

The contraction of smooth muscle, increase in vascular permeability and mucus secretion are mediated by H receptors and is associated with increase in intracellular cyclic GMP. These type of effects are competitively blocked by Hj receptor antagonists (antihistaminics) like mepyramine. 

Most of the antihistaminics (H -receptor antagonists) have similar pharmacological actions and conventionally can be discussed together. 

The second generation H -receptor antagonist cetirizine is a reacemate consisting of equal quantities of 2 enantiomers, levocetirizine [(R)-enantiomer] and dextrocetirizine [(S)-enantiomer]. In vitro and human pharmacodynamic studies have provided evidence that levocetirizine is the more active enantiomer, accounting for most or all clinical antihistaminic activity of racemic cetirizine this activity of levocetirizine is seen at half the dose of cetirizine. 

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