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Received Jul 20, 2017; Revised Nov 9, 2017; Accepted Nov 29, 2017
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1. Background
Diarrhea is the passage of three or more loose stools. It is characterized by increased gastrointestinal motility and secretion and a decrease in the absorption of fluid and electrolytes [1, 2]. Based on the duration, diarrhea is classified into 3 types: acute diarrhea (duration < 2 weeks), persistent diarrhea (duration from 2 to 4 weeks), and chronic diarrhea (duration of more than 4 weeks) [3]. Acute diarrhea is mainly caused by enteric pathogens including viruses, bacteria, and parasites whereas most cases of chronic diarrhea result from functional or inflammatory bowel disorders, malabsorption syndromes, and drugs [4, 5]. Pathogenic agents, such as Cryptosporidium, Giardia lamblia, and enteropathogenic bacteria, are thought to be the cause of persistent diarrhea [6].
Diarrheal disease is one of the leading causes of preventable death in developing countries, and it mainly affects children and infants [3]. According to the WHO and UNICEF reports, there are about 2.5 billion cases of diarrheal disease worldwide every year, and 1.9 million children below 5 years of age die from diarrhea each year, of whom most are from developing countries. Of all child deaths from diarrhea, 78% occur in African and Southeast Asian regions [7].
Many patients with a sudden onset of diarrhea have self-limited illness requiring no treatment. However, in severe cases, dehydration and electrolyte imbalance are the principal risks, particularly in infants, children, and elderly patients, thus requiring both nonpharmacologic treatments, such as oral rehydration therapy (ORT) and zinc supplements, and pharmacological treatments [8].
Antimotility and antisecretory agents are the mainstay in the treatment of diarrhea. Opioids and their derivatives continue to be widely used in the treatment of diarrhea. Diphenoxylate, difenoxin, and loperamide are commonly used opioid antidiarrheals. There are also many other drugs that have antimotility or antisecretory effects on the intestine and can be used for the treatment of diarrhea [9, 10]. Antimicrobial agents can reduce the severity and duration of infectious diarrhea [11]. Most of the enteropathogens which cause persistent diarrhea are treatable with...