H2 blockers

If antacids fail to improve symptoms, recommend ranitidine (Table 44—5). Although most H2 blockers are thought to be safe in pregnancy, ranitidine is the only agent with double-blind, randomized trials evaluating its use in this population.23... 

During lactation, sucralfate maybe the best choice for treatment of heartburn because it is not absorbed systemically.25 If symptoms are not controlled, the H2 blockers are acceptable alternatives.14,25 Avoid aluminum-containing antacids during lactation owing to reports of aluminum toxicity in otherwise healthy infants.22... 

Disruption of host defenses owing to intravenous catheters, indwelling Foley catheters, burns, trauma, surgery, and increased gastric pH (secondary to antacids, H2 blockers, and proton pump inhibitors) may place patients at higher risk for infection. Breaks in and entry into the skin provide a route for infection because the natural barrier of the skin is disrupted. Increased gastric pH can allow for bacterial overgrowth and has been associated with an increased risk of pneumonia.18... 

HT3 antagonist, prochlorperazine for emesis (avoid corticosteroids), H2 blocker for gastritis, antidiarrheal as needed (loperamide, diphenoxylate/atropine, codeine). 

Significant jejunal colonization by E. coli was found in 7 of 53 individuals before and in 4 individuals only during treatment with H2 blocker. The same species as reported during omeprazole treatment [66] were recovered [74], mostly bacteria of oropharyngeal origin. 

Furthermore, similar glucose hydrogen breath tests in the elderly with and without omeprazole [76] and normal 14C-r/-xylose breath test in healthy old people with acquired gastric hypochlorhydria (pH >6) [32] counterindi-cate that H2 blockers induce colonization with strict anaerobes of intestinal types (colonic flora) in the upper gut. 

H2 blocker, proton pump inhibitor If no improvement, endoscopy Severe bloating Prokinetic... 

This lack of complete effectiveness led to the hypothesis that a second type of histamine receptor existed. In 1972, Black et al. (55) discovered a new series of antagonists which they called H2 receptor blockers. Burimamide was the first highly effective H2 blocker, but it was poorly absorbed orally. The modified compound, metiamide, had better absorption but was found to cause granulocytopenia (57.58). Finally, cimetidine was tested and found to be a potent and relatively non-toxic antagonist (59). Cimetidine is now widely used clinically to treat duodenal ulcers, Zollinger-Ellison Syndrome and other gastric hypersecretory diseases (32). 

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. 

Extending therapy to 10 to 14 days in the above regimens may provide additional benefit. H2 blockers may be used with 2 antibiotics, but a longer... 

If antacids, anticholinergics, or H2 blockers are needed, give at least 2 hours after administration. Take with food to alleviate Gl disturbance. 

A third basic option available in the case of some therapeutic categories is to develop an over-the-counter version of a product subject to patent expiration. The strategy has been employed for example for anti-inflammatory pain relievers such as Motrin and Naprosyn, anti-ulcer therapies such as the H2 blockers Tagamet and Zantac, proton pump inhibitors such as Prilosec, and in several other therapeutic categories. However, a shift to OTC status requires approval by the FDA that the drug is safe for self-medication (Juhl 2000 McCarran 1991 Schweitzer 1997). A company will normally need to submit new clinical trial evidence to that effect. If approved by the FDA, the company receives a three-year exclusivity period for its OTC product in recognition for the new clinical trial work. 

Drugs which alter gastric pH (H2-blockers such as ranitidine, proton-pump inhibitors such as omeprazole) theoretically should alter the ionization of polar compounds, i.e., those capable of dissociation in the physiological pH range. This in turn should alter the fraction absorbed. However, while... 

The effects of histamine on body tissues and organs can be diminished in four ways inhibition of histamine synthesis, inhibition of histamine release from storage granules, blockade of histamine receptors, and physiological antagonism of histamine s effects. Of these approaches, only the inhibition of histamine synthesis has not been employed clinically. The focus of this chapter is on Hi histamine receptor antagonists it provides a brief overview of the H2 blockers and the inhibitors of histamine release. More details can be found in Chapters 39 and 40. 

Cimetidine, the first released H2-blocker, like histamine, contains an imidazole ring structure. It is well absorbed following oral administration, with peak blood levels 45 to 90 minutes after drug ingestion. Blood levels remain within therapeutic concentrations for approximately 4 hours after a 300-mg dose. Following oral administration, 50 to 75% of the parent compound is excreted unchanged in the urine the rest appears primarily as the sulfoxide metabolite. 

Unlike other imidazoles, ketoconazole Nizoral) can be absorbed orally, but it requires an acidic gastric environment patients concurrently treated with H2 blockers or who have achlorhydria have minimal drug... 

The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (H2) blockers. 

Indigestion, heartburn, and nausea are common side effects of valproate therapy. Use of the divalproex sodium preparation will help mitigate these effects. Patients may also be encouraged to take their doses with food. The symptomatic use of histamine H2 blockers, such as famotidine, is sometimes warranted. In most cases, however, dyspepsia is transient and not severe. Pancreatitis is a rare occurrence in patients receiving relatively high doses of valproate. If vomiting and severe abdominal pain develop during valproate therapy, serum amylase levels should be determined immediately. 

Work from other laboratories, some of which is discussed in Chapter 9, later showed 2-aminopyrimidones could fulfill the same functions in histamine H2 blockers as do thioureas and modified guanidines in the initial compounds many of these agents are interestingly devoid of histamine-like nuclei. Oxmetidine (66-2) represents a hybrid in that it includes moieties from both series. The p5Timidone-2-thiol (66-1) is prepared in a manner analogous to that which will be described in Chapter 9 for lupitidine condensation of this with the intermediate (63-5) leads to the replacement of the thiol by the terminal amino group. There is thus obtained oxmetidine (66-2) [69]. 

In a similar vein, the displacement of the nitrated amino group in pyrimidone (61-2), prepared in the same way as (60-5) using the methoxyl pyridinealdehyde, with the ranitidine nucleus (61-1) affords the H2 blocker donetidine (61-4) [63] after cleavage of the methyl ether. 

Alkali antacids are very effective at neutralising acid rapidly, but as described above, particulate antacids—especially aluminium salts, can cause pulmonary inflammation, and are no longer widely used. Non-particulate antacids, sodium citrate or bicarbonate, have not been shown to cause damage, and are used in conjunction with H2 blockers. They will neutralise acid already in the stomach, although pocketing of the stomach contents may prevent mixing with and neutralisation of all the contents. 

Omeprazole is more effective than H2 blockers in producing achlorhydria when repeated doses are used in treating peptic ulceration or reflux oesophagitis. However, it is less effective than these in reducing volume and acidity of stomach contents when given as a single preoperative dose, and has no advantage over H2 blockade in this situation. 

Prophylaxis of stress ulceration in intensive care units is the major interest to the anaesthetist. Here, it is given in a dose of 1 g every 6 hours via nasogastric tube. Several studies have shown sucralfate to be comparable in efficacy to H2 blockers. It has been claimed, but not proved, to result in a reduction in morbidity and mortality from nosocomial pneumonias in comparison to H2 antagonists. The latter, by raising gastric pH, eliminate the acid barrier to colonisation of the gut by pathogens, which sucralfate does not do. 

The development of H2-receptor antagonists was based on the observation that H4 antagonists had no effect on histamine-induced acid secretion in the stomach. Molecular manipulation of the histamine molecule resulted in drugs that blocked acid secretion and had no H4-agonist or antagonist effects. Like the other histamine receptors, the H2 receptor displays constitutive activity, and some H2 blockers are inverse agonists. 

Delavirdine has an oral bioavailability of about 85%, but this is reduced by antacids or H2-blockers. It is extensively bound ( 98%) to plasma proteins and has correspondingly low cerebrospinal fluid levels. Serum half-life is approximately 6 hours. 

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