Histamine antihistaminics and

Histamine, antihistamines, and antiulcer drugs like Tagamet (cimetidine) (Section 25.6B)... 

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). 

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. 

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) ... 

The term antihistamines describes drags which bind to the Hi-histamine receptor and antagonize (block) the histamine effect in Type I allergic responses. 

Antihistamines are commonly used to prevent and treat nausea and vomiting due to motion sickness, vertigo, or migraine headache.1,17 Their efficacy is presumably due to the high concentration of histamine (Hx) and muscarinic cholinergic receptors within the vestibular system. Similarly to scopolamine, antihistamines such as diphenhydramine and... 

Treatment of ocular allergy is aimed at slowing or stopping these processes. Antihistamines block the histamine receptors and some prevent histamine production and/or inhibit mediator release from the mast cells.15 Mast cell stabilizers inhibit the degranulation of mast cells, preventing mediator release. Some topical agents have multiple mechanisms of action, combining antihistaminic, mast cell stabilization, and antiinflammatory properties (Tables 60-3 and 60-4).16... 

Thurmond RL, Gelfand EW, Dunford PJ The role of histamine Hj and H4 receptors in allergic inflammation the search for new antihistamines. Nat Rev DrugDiscov 2008 7 41-53. 

The newer antihistaminics agents e.g. Azelastme inhibits histamine release and also inflammatory reactions evoked by leukotrienes and plasma activating factor (PAF). It is used for seasonal and perennial allergic rhinitis in the form of nasal spray. Mizolastine, a non-sedating antihistaminic is used in allergic rhinitis and urticaria. Ebastine, another non-sedating antihistaminic is used in nasal and skin allergies. 

Histamine is a chemical messenger that mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and possibly neurotransmission in parts of the brain. Histamine has no clinical applications, but agents that interfere with the action of histamine (antihistamines) have important therapeutic applications. 

Q4 Antihistamines are effective in managing many of the troublesome symptoms of allergic rhinitis. Histamine is a neurotransmitter and a mediator of type 1 hypersensitivity reactions, such as urticaria and hay fever. There are several types of histamine receptors and these allergic conditions can be treated with Hi receptor antagonists, such as promethazine, chlorphenamine and fexofenadine. First-generation antihistamines, such as promethazine, cause sedation and possess side effects associated with actions on muscarinic receptors. Fexofenadine is a newer drug with a longer duration of action, which does not sedate the patient. 

Histamine produces a wide range of physiological effects in the body. Excess histamine is responsible for the runny nose and watery eyes symptomatic of hay fever. It also stimulates the overproduction of stomach acid, and contributes to the formation of hives. These effects result from the interaction of histamine with two different cellular receptors. We will learn more about antihistamines and antiulcer drugs, compounds that block the effects of histamine, in Section 25.6. 

The signal characteristic of the second-generation antihistamines is their freedom from sedation (2,16). The relative lack of sedative properties in the second-generation antihistamines has been ascribed to their relative hydrophi-licity. Little is known about intracerebral concentrations of antihistamines and their metabohtes, but positron emission tomography has shown that the first-generation antihistamine chlorphenamine occupied a larger fraction of brain histamine Hi receptors than terfenadine (SEDA-20,164). Differential affinity for, or different actions on, central and peripheral Hi receptors (SEDA-21,171) could also explain variations in sedative effect, but differences in receptor binding have only been shown for loratadine in vitro (45). 

Rapid intravenous infusion of deferoxamine (more than 25 mg/kg over 30 minutes) can cause vertigo, hypotension, diffuse erythema, and generalized pruritus (11). Such reactions reverse on withdrawal of the infusion, although occasionally a fluid bolus and/or an antihistamine may be needed to reverse the symptoms more rapidly. This reaction is considered to be due to histamine release and not to be immunological in nature patients can be safely treated later at a lower rate of infusion. 

Doenicke A, Moss J, Lorenz W, Mayer M, Rau J, Jedrzejewski A, Ostwald P. Effect of oral antihistamine premedication on mivacurium-induced histamine release and side effects. Br J Anaesth 1996 77(3) 421-3. 

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