Antihistamine examples

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet "antihistamines." This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

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 sedation side effect commonly observed on administration of classical antihistaminic drugs has been attributed in part to the ease with which many of these compounds cross the blood brain barrier. There have been developed recently a series of agoits, for example, terfenadine (198), which cause reduced sedation by virtue of decreased penetration into the CNS. This is achieved by making them more hydrophilic. Synthesis of a related compound, ebastine (197),... 

Antihistamines are drags used to counteract the effects of histamine on body organs and structures. Examples of antihistamines include diphenhydramine (Benadryl), loratadine (Claritin), fexofenadine (Allegra), and cetirizine (Zyrtec). A new antihistamine, deslorata-dine (Clarinex), is die active metabolite of loratadine and is intended to eventually replace loratadine (Claritin). Topical corticosteroid nasal sprays such as fluticasone propionate (Flonase) or triamcinolone ace-tonide (Nasacort AQ) are also used for nasal allergy symptoms. See Chapter 56 for more information on die topical corticosteroids. 

Diamines find considerable use as pharmaceuticals here is one example followed by two diamine problems. Histapyrrodine (14) is used as an antihistamine. 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

Yet another related approach to pharmacotherapy management is step protocols or step therapy. Step protocols limit access to certain drugs until less costly alternative drugs have been tried first. For example, a step protocol might require a patient to have tried a relatively low-cost antihistamine, such as chlorpheniramine, before being prescribed a more expensive nonsedating antihistamine. Step therapy procedures were in place at 68.5% of HMOs in 1998 [1]. 

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. 

Medications for symptomatic relief from vertigo consist of antiemetics, benzodiazepines and antihistamines. They are all mostly aimed at the psychological consequences of dizziness and can all have highly unfavourable side effects, for example, sedation, anticholinergic effects and insomnia. The psychological consequences of dizziness in elderly should rather be treated with information about the condition, supportive help actions and increased social activities, than with drugs. 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

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. 

Significant side effects have been estimated to occur in about 5% of patients on TCAs, most of these effects being attributed to their antimuscarinic properties, for example, blurred vision, dry mouth, tachycardia and disturbed gastrointestinal and urinary tract function. Orthostatic hypotension due to the block of alphai adrenoceptors and sedation resulting from antihistaminic activity frequently occur at therapeutic doses, particularly in the elderly. Excessive sweating is also a fairly common phenomenon, but its precise mechanism is uncertain. In the elderly patient, the precipitation of prostatic hypertrophy and glaucoma by the TCAs is also a frequent cause of concern. 

Domperidone is a dopamine antagonist that acts on the chemoreceptor trigger zone. It can therefore be used as an anti-emetic in nausea and vomiting, for example, to counteract side-effects of cytotoxic therapy and to treat nausea associated with dopaminergic drugs used in Parkinson s disease. Unlike hyoscine butlybromide and antihistamines, domperidone is ineffective in motion sickness. 

It is based on the action of a drug on a particular biochemical process. For example, all antihistamines inhibit the action of the compound, histamine which causes inflammation in the body. There are various ways in which action of histamines can be blocked. You will learn about this in Section 16.3.2. 

An important example of PLP-dependent amino acid decarboxylation is the conversion of histidine into histamine. Histamine is often involved in human allergic responses, e.g. to insect bites or pollens. Stress stimulates the action of the enzyme histidine decarboxylase and histamine is released from mast cells. Topical antihistamine creams are valuable for pain relief, and oral antihistamines are widely prescribed for nasal allergies such as hay fever. Major effects of histamine include dilation of blood vessels, inflammation and swelling of tissues, and narrowing of airways. In serious cases, life-threatening anaphylactic shock may occur, caused by a dramatic fall in blood pressure. 

There are also known cases of drug enantiomers that possess completely different therapeutic properties. The (+)-2/ ,35 -stereoisomer of propoxyphene (dextropropoxyphene) is marketed as an analgesic agent, whereas its enantiomer ( )-(25, 3/ )-propoxyphene (levopropoxyphene) is available as an effective anti-tussive agent [3]. The enantiomers of some chiral drugs are known to possess essentially identical qualitative and quantitative pharmacological activities, for example, the antihistamine promethazine, which is marketed as a racemate [5]. 

It is usual to give a sedating antihistamine, for example chlorphenamine 10 mg by intramuscular or slow intravenous injection, because of the relatively short half-life of epinephrine (adrenaline), and because of the active role of histamine in anaphylaxis. In addition, the inflammatory reaction can be moderated by the administration of a corticosteroid, such as hydrocortisone 200 mg by intramuscular or slow intravenous injection. Corticosteroids may take several hours to act, but can be of some help in so-called biphasic anaphylactic reactions. 

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