ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03530.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Stress ulceration, a disease associated with the stress of severe injury, sepsis, and organ failure, has declined in frequency during the last decade. Factors contributing to this decrease include more rapid transport of trauma patients, early resuscitation, avoidance and treatment of complications, and prophylactic maintenance of increased gastric mucosal pH. The pathophysiology of these lesions remains to be elucidated completely; however, both aggressive factors (acid, duodenal reflux, etc.) and a deficiency in defensive mechanisms (gastric mucosal blood flow, gastric mucosal barrier, mucus, bicarbonate, etc.) play a role in their inception. The hemorrhagic complication of stress ulcer, which is usually seen between the fifth and tenth days after admission, remains a sequela associated with a significant rate of mortality.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03531.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Advances in the care of critically ill patients and in diagnostic techniques, such as fiberoptic endoscopy, have enabled greater recognition of stress‐related mucosal damage (SRMD). This condition is distinguished from chronic peptic ulcer disease by its greater number of lesions, proximal location in the acid‐producing portion of the stomach, and superficial bleeding. Endoscopy is considered the best method for detecting and monitoring mucosal damage. The onset of SRMD occurs early, within hours of the traumatic insult. Pharmacologic treatment has been oriented toward suppressing intraluminal acid and enhancing mucosal defense mechanisms. Antacid therapy is considered the best method for treatment of SRMD, although extensive experience has been gained with the H2‐receptor antagonists. The vast majority of experience with the H2‐receptor antagonists has been with cimetidine, which is as effective as antacids, as shown by endoscopy. Investigations of alternative forms of therapy (e.g., prostaglandins) are in p

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03532.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Cell injury produced by hydrochloric acid is the final common denominator for stress‐related mucosal damage. Actions of therapeutic agents designed to prevent such damage are directed toward either inhibiting acid secretion or stimulating protective mechanisms. Newer agents that fall into the former category include omeprazole, an inhibitor of the H+‐K+–ATPase pump, prostaglandins, and somatostatin. In addition to inhibiting acid, prostaglandins stimulate mucus and bicarbonate secretion and therefore provide a two‐pronged protective action. Tranexamic acid is an antifibrinolytic agent that is postulated to promote clotting at bleeding sites in upper gastrointestinal lesions. Analyses of composite data suggest that (1) prostaglandin E preparations appear to be as effective as currently recognized forms of therapy, such as antacid and H2‐receptor antagonist administration; (2) little enthusiasm can currently be generated for use of somatostatin or tranexamic acid; and (3) omeprazole is a theoretically attractive agent that remains to be tested in the prophylactic treatment of gastrointestinal ulceration due to seve

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03533.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The H2‐receptor antagonists cimetidine, ranitidine, and famotidine are well tolerated, with a low frequency and similar spectrum of adverse effects. The occasional problematic effects that have been associated with these agents include central nervous system symptoms (mental confusion, headache, and depression), rare cases of thrombocytopenia, and cardiovascular events related to the rate of intravenous infusion. Severe renal and hepatic impairment appear to be associated with a higher occurrence of central nervous system effects. Because the H2‐receptor antagonists elevate gastric pH, bind to and inhibit the hepatic cytochrome P‐450 enzyme system, and undergo renal tubular secretion, competition with other drugs sharing these pathways has resulted in a number of drug interactions, most of which are not clinically significant. The interaction that occurs with theophylline and warfarin when the cytochrome P‐450 enzyme system is inhibited by cimetidine and ranitidine requires monitoring. Recent data suggest that administering cimetidine 800 mg at bedtime has less effect on the serum concentrations of warfarin and theophylline than other dosing regimens. Evidence to date indicates that famotidine does not bind to cytochrome P‐450 to a significant extent, and interactions with drugs metabolized by this system have not been reported; however, clinical experience with this agent is ver

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03534.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Epidemiologic evidence has shown that elevated levels of high‐density lipoproteins (HDL) protect against the development of coronary heart disease (CHD). These observations have prompted the evaluation of various factors thought to affect HDL and its subspecies, HDL2and HDL3. Numerous behavioral and physiologic factors have been shown to elevate HDL levels. These are currently being researched as potential tools in preventing CHD. Several pharmacologic agents are known to alter HDL levels. Studies show that patients with peptic ulcer disease treated with the H2‐receptor antagonist cimetidine show significant elevations in their HDL, HDL2, and HDL3profiles. In contrast, ranitidine has no effect, or may even decrease HDL levels. These divergent effects may be related to differences in pharmacologic activity unrelated to H2‐receptor blockade. It should be noted that many of the variables affecting HDL levels were not controlled in these studies, and definite conclusions should not be extrapolated to the general population at risk for CHD. Currently, well‐controlled trials to study the effect of cimetidine on HDL levels are in p

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03535.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Suppressor T lymphocytes play a major regulatory role in the function of the immune system. Since the discovery of histamine (H2) receptors on the surface of these immune cells, studies have demonstrated that cimetidine diminishes the effect of suppressor T cells in both cellular‐ and humoral‐mediated (antibody) immune reactions. Preliminary clinical results demonstrate that cimetidine has a beneficial effect on a variety of immune functions. An antineoplastic effect among tumor‐bearing animals has also been found, suggesting the drug may be effective against certain human cancers, probably as an immune potentiator. Cimetidine has been used in the treatment of human cancer in combination with interferon or coumarin and as a single agent. Modest tumor response rates have been observed. The finding that cimetidine accelerates healing of herpesvirus infections is intriguing. These encouraging, albeit preliminary, results emphasize the need for additional studies on the drug's antiviral prope

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03536.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Acetaminophen, a drug frequently taken in intentional and accidental overdose, causes liver toxicity when concentration of the cytochrome P‐450‐derived metabolite exceeds the metabolic capacity of available glutathione. Present treatment of acetaminophen overdose involves oralN‐acetylcysteine (NAC), which enhances liver glutathione synthesis. An alternative or additive approach to therapy would be to inhibit the formation of the toxic metabolite by inhibiting the cytochrome P‐450 system. The H2‐receptor antagonist cimetidine inhibits the cytochrome P‐450 system, does not interfere with the administration or function of NAC, and therefore affords additive protection. Also, it has little effect on the nontoxic routes of elimination of acetaminophen and is itself quite nontoxic. That cimetidine protects against acetaminophen toxicity in animal models has been demonstrated on the basis of improved survival, as well as decreases in several critical elements used to monitor acetaminophen toxicity: classic histologic changes, aminotransferase activity, metabolite covalent binding, and liver glutathione depletion. Administration of cimetidine well after the overdose is also protective. In contrast, animal models of acetaminophen toxicity demonstrate that ranitidine does not afford protection from acetaminophen hepatotoxicity. Clinical data in well‐done trials in humans will be needed to support the experimenta

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03537.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1987.tb03538.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY