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.