Hj antagonists

Histamine Hj-antagonists such as cimetidine or ranitidine can be heipfu when combined with H,-antihistamines... 

Hj-antagonists alone, such as cimetidine or ranitidine, have a modest effect on cutaneous flush reaction and maybe also on the heart [14, 52]. However, when applied they should be given together with Hj-antagonists. There are some studies showing a beneficial effect of combined H - and Hj-antagonist treatment or pretreatment in anaphylaxis [46, 53]. 

Antihistamine drags are classified as antagonists of Hj and receptors, and quantitatively speaking Hj antagonists dominate. Moreover, the term antihistamine drag is associated more with Hj antagonists. H2 blockers exhibit a specific effect on histamine receptive sites located in walls of the stomach and they significantly increase secretion of hydrochloric acid. 

Scopolamine is useful for prevention of motion sickness when the motion is very stressful and of short duration. A transdermal preparation (Transderm-Scop) with a 72-hour duration of action has been marketed for this purpose. Blockade of chohnergic sites in the vestibular nuclei and reticular formation may account for the effectiveness of this agent. When the motion is less stressful and lasts longer, the antihistamines (Hj-antagonists) are probably preferable to the antimus-... 

Another important use of Hj-antagonists is in the treatment of motion sickness. Diphenhydramine (Benadryl), dimenhydrinate (Dramamine), cyclizine (Marezine), and meclizine (Antivert) have anticholinergic activity and are the preferred antihistaminic agents for reducing the symptoms of motion sickness. 

For patients who do not respond appropriately, adding antacid or Hj-antagonist may provide better results... 

The Hj antagonists are metabolized in the liver, and the metabolites are excreted in the urine. Diphenhydramine is mainly metabolized via N-demethylation, and its primary metbolite is monodesmethyldiphenhy-dramine (Scavone et al., 1998). These agents are able to induce hepatic microsomal enzymes and may increase the rate of their own metabolism. The half-life of diphenhydramine is approximately 4 hours. In general, the half-life is decreased in children and increased in patients with severe liver disease (Babe and Serafin, 1996). 

Indolylpiperidine compounds are known as Hj antagonists for treatment of allergic rhinitis. Analogous piperidinyl-pyrrolopyridine derivatives, 146, are under investigation for their selectivity and potency as Hj antagonists <2005BML1165>. 

Classically, these receptors have also been divided into three groups. The first of these, the Hj receptors, were described by Schild in 1966. The Hj receptors were discovered in 1972 by Black et al. The Hj receptor subtype was described by Arrang in 1983. The Hj receptor is found in the smooth muscle of the intestines, bronchi, and blood vessels and is blocked by the classical antihistamines. The Hj receptor, present in gastric parietal cells, in guinea pig atria, and in the uterus, does not react to H, blockers but only to specific Hj antagonists. Hj receptors also appear to be involved in the immunoregulatory system and may be present in T lymphocytes, basophil cells, and mast cells. Hj receptors are found predominantly in brain but are also localized in stomach, lung, and cardiac tissue. 

Stimulation of gastric acid secretion is the most important response it is blocked only by Hj antagonists. As mentioned before, the hormone gastrin may be involved in histamine release, because Hj antagonists block gastrin-induced acid secretion. 

H2 Antagonists and the Treatment of Peptic Ulcers. Treatment of peptic ulcers is a complicated and multilevel therapy in which Hj antagonists are very successful and widely used (and abused). Peptic ulcers may affect either the stomach (gastric ulcers, less common overall but more common in people with iatrogenic [i.e., physician-induced] ulcers from the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) or the duodenum (duodenal ulcers). The lining of the stomach or duodenum is attacked by the digestive juices to such an extent that the protective mucous layer on the surface has... 

Several lines of evidence suggest a role for Hj receptors in cognitive processes. The use of Hj antagonists in learning and memory disorders has been suggested. Thioperamide, a prototypic Hj antagonist, enhances arousal patterns in cats, an observation which has been confirmed using other nonthiourea Hj blockers. 

Antimotion sickness effect Several Hj-antagonists have significant property in preventing motion sickness. This effect was first observed with drug, dimenhydrinate and subsequently with other drugs like diphenhydramine, promethazine and other piperazine derivatives. 

Anticholinergic effects Many of the Hj-antagonists also tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. The newer agents, terfenadine and astemizole have no effect on muscarinic receptors. 

Side effects include loss of appetite, nausea, vomiting, epigastric distress, constipation or diarrhoea. Side effects due to antimuscarinic actions of Hj-antagonists include dryness of mouth, bladder disturbances. 

Iatrogenic Reactions broadly refer to any adverse reactions that are unintentionally produced by physicians in their patients. For example, one of the side effects of many antihistaminic preparations (Hj antagonists) such as ethanolamine derivatives (prototype diphenhydramine) is heavy sedation. Although sedation may be desirable for some patients, it may interfere with daytime activities, and this needs to be considered when prescribing such medications. Other antihistaminic preparations (also 11 antagonists) such as piperidine derivatives (prototypes terfenadine or astemizole) have no sedative properties (Figure 3.2). 

Several of the older generation antihistamines are used exclusively for situations that do not involve an allergic reaction. For example, some demonstrate significant antiemetic, antimotion sickness, antiparkinsonian, antitussive, and local anesthetic actions (some Hj antagonists are more potent than procaine). They can be found in many OTC products, particularly for the relief of symptoms from the common cold and allergies, as well as by prescription. The effectiveness of the agents in the treatment of motion sickness and Parkinson s disease may be attributed to their anticholinergic actions. 

Note the term Hj blockers, Hj antagonists and antihistamines are used to denote the same meaning. 

Action on organs other than the target organ (e.g., peripheral tachycardic and hypertensive effects of dopamine after systemic application of the anti-Parkinson drug L-dopa, sedative side effects of lipophilic histamine Hj antagonists). 

Burch RM, MAIS DE, SaUSSY DL Jr, HaLUSHKA PV. Solubilization of a thromboxane A /prostaglandin Hj antagonist binding site from human platelets. Proc Natl Acad Sd USA 82 7434-7438,1985. 

A PPIs are most effective when given 30 minutes before a meal or breakfast (and not with food). This ensures that large amounts of inactive H+/K+-ATPase pumps are present. PPIs should not be coadministered with Hj antagonists. PPIs work best If taken routinely to promote healing rather than on an as-needed basis. 

C It is recommended that all patients receiving paclitaxel receive pretreatment to reduce the risk and severity of hypersensitivity reactions. The preferred regimen includes a combination of a corticosteroid (such as dexamethasone), an antihistamine (diphenhydramine or equivalent), and an Hj antagonist (such as cimetidine or ranitidine). Omeprazole and other PPIs will not block Hj-receptor sites and do not provide protection against hypersensitivity reactions. 

Figure 6.2 Gastric fluid pH measurements after famotidine was administered by nasogastric tube at dose rates of 0.5 ( ), 1.0 ff) and 2.0 mg/kg (A) to a horse that had not been fed for 18 h. Gastric fluid was aspirated through a weighted nasogastric tube at 15 min intervals for 1 h before and from 45 min after administration. The gastric fluid pH dose-response in this horse typify the poor (0.5 mg/kg), intermediate (1.0 mg/kg) and good (2.0 mg/kg) responses to oraliy administered Hj antagonists in horses.

---