Rabbani G H
International Centre for Diarrhoeal Disease Research, Clinical Sciences Division, Dhaka, Bangladesh.
Dan Med Bull. 1996 Apr;43(2):173-85.
The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes. In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions.
这些研究的主要目的是确定潜在的抗分泌和抗菌药物在治疗霍乱弧菌和产肠毒素大肠杆菌（ETEC）所致腹泻方面的临床疗效和安全性。所评估的药物有氯丙嗪（CPZ）、烟酸、黄连素、吲哚美辛、氯喹、四环素、呋喃唑酮和生物制剂Florin。此外，还研究了前列腺素（PGs）在霍乱性腹泻发病机制中的作用。药物研究作为安慰剂对照的随机临床试验，在因霍乱弧菌和ETEC导致急性腹泻的患者中进行。所有患者均接受静脉或口服补液溶液（ORS），但除研究药物外未使用其他药物。结果表明，CPZ（1mg/kg或4mg/kg）、黄连素（200mg）和烟酸（2g）均可使腹泻患者的粪便量减少30%至50%以上，且无明显副作用。似乎黄连素对ETEC腹泻比对霍乱更有效。然而，氯喹、吲哚美辛、可乐定和生物制剂Florin没有临床有用的效果。在抗菌药物中，发现单剂量四环素对霍乱有效，因为与呋喃唑酮相比，该药物显著（p<0.05）将总粪便量从20.9±15.9降至10.5±8.6（6天内的升数，平均值±标准差）。除抗菌和抗分泌药物外，其他药物也被评估用于霍乱治疗。已表明，用生物制剂Florin（冻干粪肠球菌的细菌制剂）治疗并未显著（p>0.05）减少霍乱患者的液体流失。在动物身上进行的其他研究表明，单独或与氯阻断剂9-蒽羧酸（A9C）联合使用短链葡萄糖聚合物治疗，可显著减少分泌性腹泻大鼠模型中的肠道分泌。首次证明，急性霍乱期间空肠前列腺素（PG）E2浓度显著升高，且与粪便量和腹泻持续时间相关。此外，还表明，用PG合成的强效抑制剂吲哚美辛治疗，除了减少水和电解质的净分泌外，还可显著降低急性霍乱成人患者的空肠PGE2分泌量。总结结果得出：（1）CPZ、黄连素和烟酸是潜在的止泻剂；（2）PGs参与霍乱的发病机制；（3）四环素和呋喃唑酮是治疗霍乱有效的抗菌药物；（4）葡萄糖短链聚合物（与氯阻断剂9-蒽羧酸一起使用）是口服补液溶液中更好的碳水化合物来源。
