H 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. 

Histamine H,-antagonists For intravenous infusion diphenhydramine, dimetindene and ciemastine are avaiiabie. There are no controiied studies for the new non-sedating antihistamines in the treatment of anaphyiaxis... 

The newer H -antagonists such as terfenadine and astemizole are claimed to have little or no sedative action. Astemizole is also claimed to be free of autonomic blocking effects. Loratidine is claimed to have little autonomic and CNS blocking effects. 

H -antagonists are well absorbed from the gastrointestinal tract. Following oral administration, antihistaminic effect is manifested within 30 minutes, peak plasma concentration is achieved in 2 to 3 hours and effects usually last 4 to 6 hours. However, drugs in piperazine subgroups especially chlorcyclizine and meclizine, the actions persists for 8 to 12 and 12 to 24 hours respectively. 

H5 ersensitivity reactions To prevent allergic reactions or to treat their symptoms, in which histamine is the primary mediator, the H -antagonists are the drugs of choice and are often quite effective. They are used primarily to treat allergic reactions produced by the release of histamine e.g., edematous states, pruritus, allergic rhinitis and urticaria. They are generally more effective in acute conditions and are used only for symptomatic relief. 

Antiparkinsonism Based on anticholinergic property, some H -antagonists such as diphenhydramine can be used in the early stages of treatment of parkinsonism. 

Local anaesthetics In patients allergic to procaine H -antagonists, such as diphenhydramine and tripelennamine have been used successfully as local anaesthetic. 

It is a cromolyn analogue. It is an antihistaminic (H antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria. It is absorbed orally and well tolerated. Bioavailability is 50% due to first pass metabolism and is primarily metabolized. The common side effects include dry mouth, sedation, dizziness and nausea. 

Some of the H antagonists, especially diphenhydramine, have significant acute suppressant effects on the extrapyramidal symptoms associated with certain antipsychotic drugs. This drug is given parenterally for acute dystonic reactions to antipsychotics. 

Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, diazepam,dicumarofdisulfiram,estrogens, H -antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone... 

The sulcs of antagonists of Hi receptors, used in the treatment of allergic diseases, represent I F of the overall pharmaceutical market, i.e.. SI.7 billion (U.S.i. Sales of H. antagonists, used mainly in peptic ulcer disease and esophageal rellux. represent. 1.5 if of the world market. 

Effects of histamine on blood pressure and heart rate in humans. Histamine was infused at 40 u g/kg/h for 5 minutes as shown at the top of the panel. (Modified and reproduced, with permission, from Torsoli A, Lucchelli PE, Brimblecombe RW [editors] H-Antagonists H2 Receptor Antagonists in Peptic Ulcer Disease and Progress in Histamine Research. Excerpta Medica, 1980.)... 

It is remarkable that, for histamine, very few compounds of plant origin have been found to have JI (or H2, H3, H4) -blocking properties (Fig. 18.17). a-Mangostin [28] is an example, although remarkably this compound (a competitive H, antagonist) does not carry a basic function. A basic tertiary amino group is also absent in cicletanide, an intriguing compound that has a chiral center and in which the antihistaminic activity resides in the levo isomer (Fig. 18.17). Rocastine and temelastine are two other antihistaminic compounds with unusual structures (Fig. 18.12). 

Burch RM, Mais DE, Saussy DL Jr, Haludika PV. Solubilization of a thromboxane A /prostaglanding H, antagonist binding site from human platelets. Proc Nall Acad Sd USA 1985 82 7434-8... 

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