Anti-diarrheals-II

Diarrhoea Opioids Loperamide, Morphine, Codeine Loperamide, Morphine, Codeine Mode of action: 1. increase tone of both small and large bowel and reduce intestinal motility (enhances fluid and electrolyte reabsorption) ; 2. increase the sphincter tone and decrease secretory activity along GIT

Diarrhoea Loperamide It is a synthetic opioid agonist that has a high affinity for, and exerts a direct action on  opiate receptors in the gut wall; It is a synthetic opioid agonist that has a high affinity for, and exerts a direct action on  opiate receptors in the gut wall; also has a high first-pass metabolism so very little reaches the systemic circulation; also has a high first-pass metabolism so very little reaches the systemic circulation; effective in reducing the duration of diarrhea (25 vs 40 hrs with placebo) effective in reducing the duration of diarrhea (25 vs 40 hrs with placebo)

Diarrhoea Loperamide 50 fold more potent than morphine and 2- 3 times more potent than diphenoxylate in its effect on GI motility, but penetrates the CNS poorly, thus has lower risk of CNS side effects; Other mechanisms: 1. disruption of cholinergic and non-cholinergic mechanisms of peristalsis, 2. inhibition of calmodulin function and 3. inhibition of voltage dependent Ca channels Other mechanisms: 1. disruption of cholinergic and non-cholinergic mechanisms of peristalsis, 2. inhibition of calmodulin function and 3. inhibition of voltage dependent Ca channels

Diarrhoea Loperamide Indications: traveller’s diarrhoea traveller’s diarrhoea non-specific acute diarrhoea non-specific acute diarrhoea chronic diarrhoea associated with inflammatory bowel disease chronic diarrhoea associated with inflammatory bowel disease AAP does not recommend use in children < 6 years old Used when patient is afebrile or have mild fever and does not have bloody stool Used when patient is afebrile or have mild fever and does not have bloody stool

Diarrhoea Clinical use should not be used in patients with severe ulcerative colitis, since toxic megacolon may be precipitated may prolong duration of diarrhea in patients with Shigella or Salmonella infection in patients with irritable bowel syndrome with predominant diarrhea, loperamide in doses of 2-4 mg QID may lead to substantial clinical improvement (combined with reduction of fiber, use of anticholinergic agents, & supportive counseling)

Diarrhoea Loperamide Dosage & Administration dosage forms: caplets (2 mg), and liquid (1 mg/5ml) dosage forms: caplets (2 mg), and liquid (1 mg/5ml) Dose: 4 mg initially, then 2 mg after each loose stool/ Do not exceed 16 mg/day Dose: 4 mg initially, then 2 mg after each loose stool/ Do not exceed 16 mg/day Consult product instructions for pediatric dose Consult product instructions for pediatric dose

Diarrhoea Loperamide Side effects: At usual doses: few side effects other than occasional dizziness and constipation Other: abdominal pain and distension, nausea, vomiting, dry mouth, fatigue and hypersensitivity reactions It may worsen effects of invasive bacterial infections and may cause toxic megacolon in antibiotic-induced diarrhoea If abdominal distension, constipation, or ileus occurs, loperamide should be discontinued

Diarrhoea Loperamide Contraindication Loperamide should not be used in patients with fecal leukocytes, high fever, or blood or mucus in the stool (dysentery); Loperamide should not be used in patients with fecal leukocytes, high fever, or blood or mucus in the stool (dysentery); Loperamide may cause paralytic ileus in patients with desentery Loperamide may cause paralytic ileus in patients with desentery Paralytic ileus: paralysis or inactivity of the intestine that prohibits the passage of material within the intestine. May be a result of anticholinergic drugs, injury or surgery

Diarrhoea The most widely used prescription drugs for diarrhea: diphenoxylate (with atropine), a weak analog of meperidine Difenoxin: active metabolite of diphenoxylate available as prescription medication

Diarrhoea Adsorbents Kaolin, pectin, attapulgite and bismuth subsalicylate; Kaolin, pectin, attapulgite and bismuth subsalicylate; Kaolin: a natural hydrated aluminum silicate. Not absorbed from GIT, 90% metabolized in gut and excreted in faeces Kaolin: a natural hydrated aluminum silicate. Not absorbed from GIT, 90% metabolized in gut and excreted in faeces Attapulgite is another naturally occur clay mineral, consisting of hydrous Mg-Al-silicate; Attapulgite is another naturally occur clay mineral, consisting of hydrous Mg-Al-silicate; kaolin & attapulgite have varying and relatively weak adsorptive properties in respect to diarrhoea producing bacteria kaolin & attapulgite have varying and relatively weak adsorptive properties in respect to diarrhoea producing bacteria

Diarrhoea Adsorbents Pectin is a purified carbohydrate obtained from the rind of citrus fruit of pomace (crushed apple); its mode of action is uncertain; Pectin is a purified carbohydrate obtained from the rind of citrus fruit of pomace (crushed apple); its mode of action is uncertain; Bismuth subsalicylate: claimed to pocess adsorbent properties; large doses are required and salicylate absorption may occur (be cautious!) Bismuth subsalicylate: claimed to pocess adsorbent properties; large doses are required and salicylate absorption may occur (be cautious!)

Diarrhoea Adsorbents Mode of action: 1. adsorb the microbial toxins and micro- organisms to their own surfaces drugs not absorbed from the GIT  toxins and MOs are excreted in stool; drugs not absorbed from the GIT  toxins and MOs are excreted in stool; 2.Hydrophilic adsorbents (e.g. pectin and bulk- forming agents; ispaguala, methylcellulose, and sterculia ), bind water within the intestine causing watery stool to become more formed

Diarrhoea Adsorbents the main constituents in the antidiarrhoeal preparations for young children (whom opiates and antimuscarinics are contraindicated); the main constituents in the antidiarrhoeal preparations for young children (whom opiates and antimuscarinics are contraindicated); not absorbed from GIT  harmless and safe to use not absorbed from GIT  harmless and safe to use Debate: reduce evacuation of faeces- prolong presence of pathogens/toxins in bowel. Adsorption: non-specific process (medicines) Debate: reduce evacuation of faeces- prolong presence of pathogens/toxins in bowel. Adsorption: non-specific process (medicines)

PROBIOTICS: AN UPDATE

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Diarrhoea Background Probiotics are live organisms that are ingested to provide therapeutic or preventative benefit for the host. The most commonly used are the lactic acid- producing bacteria bifidobacteria and lactobacilli. Probiotics also include the yeast Saccharomyces boulardii. Probiotics are commonly promoted to strengthen the immune defenses. Probiotics are live organisms that are ingested to provide therapeutic or preventative benefit for the host. The most commonly used are the lactic acid- producing bacteria bifidobacteria and lactobacilli. Probiotics also include the yeast Saccharomyces boulardii. Probiotics are commonly promoted to strengthen the immune defenses. 17

Diarrhoea Bifidobacteria spp Saccharomyces boulardii 18

Diarrhoea Probiotics, Beneficial Microbes Beneficial microbes such as bifidobacteria live in the intestinal ecosystem with potentially pathogenic bacteria. Beneficial microbes prevent the overgrowth of “bad bacteria” by producing antimicrobial agents. Additionally, beneficial microbes competitively limit pathogenic bacterial overgrowth by occupying receptor sites and vying for space and nutrients. Beneficial microbes may also increase intestinal production of mucin, which stimulates the production of mucus, forming a protective barrier on the intestinal lining Beneficial microbes such as bifidobacteria live in the intestinal ecosystem with potentially pathogenic bacteria. Beneficial microbes prevent the overgrowth of “bad bacteria” by producing antimicrobial agents. Additionally, beneficial microbes competitively limit pathogenic bacterial overgrowth by occupying receptor sites and vying for space and nutrients. Beneficial microbes may also increase intestinal production of mucin, which stimulates the production of mucus, forming a protective barrier on the intestinal lining 19

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Diarrhoea In order to be effective: In order to be effective: probiotics must be able to withstand a wide range of pH variation. Many microbes cannot withstand the protective acid barrier of the stomach and the effects of bile. probiotics must be able to withstand a wide range of pH variation. Many microbes cannot withstand the protective acid barrier of the stomach and the effects of bile. must also be able to colonize the gut and be able to attach to the intestinal epithelium.must also be able to colonize the gut and be able to attach to the intestinal epithelium. Additionally, the probiotic should not disturb healthy intestinal microbesAdditionally, the probiotic should not disturb healthy intestinal microbes 21

Diarrhoea Probiotic Bacteria and Yeasts Bifidobacteria are anaerobic, rod-shaped, gram-positive bacteria. Bifidobacteria are the most prominent beneficial microbes in the colon. Bifidobacteria produce antimicrobial substances that have a broad spectrum of antimicrobial activity Bifidobacteria are anaerobic, rod-shaped, gram-positive bacteria. Bifidobacteria are the most prominent beneficial microbes in the colon. Bifidobacteria produce antimicrobial substances that have a broad spectrum of antimicrobial activity 22

Diarrhoea Bifidobacteria that are commonly used as probiotics include Bifidobacterium longum, B. breve, B. infantis, B. bifidum, B. lactis, and B. adolescentis. Bifidobacteria supplements are most commonly combined with other probiotics. Bifidobacteria that are commonly used as probiotics include Bifidobacterium longum, B. breve, B. infantis, B. bifidum, B. lactis, and B. adolescentis. Bifidobacteria supplements are most commonly combined with other probiotics. Lactobacilli are a group of gram-positive rods that are obligate and facultative anaerobes. 23

Diarrhoea Other bacteria sometimes used as probiotics include Streptococcus thermophilus and Leuconostoc species. The yeasts Saccharomyces boulardii and S. cerevisiae are also used Other bacteria sometimes used as probiotics include Streptococcus thermophilus and Leuconostoc species. The yeasts Saccharomyces boulardii and S. cerevisiae are also used 24

Diarrhoea Probiotics for Diarrhea Probiotics may be useful as adjunctive treatment of adults and children with infectious diarrhea. Several species of Lactobacillus seem to reduce the duration of diarrhea, particularly in rotaviral infections. Probiotics may be useful as adjunctive treatment of adults and children with infectious diarrhea. Several species of Lactobacillus seem to reduce the duration of diarrhea, particularly in rotaviral infections. For antibiotic-associated diarrhea, Lactobacillus rhamnosus GG, S. boulardii, and probiotic mixtures appear to be effective prophylactic agents. Given along with antibiotics, these probiotics can reduce the incidence of diarrhea by about 60% to 65%. The effectiveness of probiotics on treatment of antibiotic-associated diarrhea is less clear.For antibiotic-associated diarrhea, Lactobacillus rhamnosus GG, S. boulardii, and probiotic mixtures appear to be effective prophylactic agents. Given along with antibiotics, these probiotics can reduce the incidence of diarrhea by about 60% to 65%. The effectiveness of probiotics on treatment of antibiotic-associated diarrhea is less clear. 25

Diarrhoea Results of studies looking at probiotics for traveler’s diarrhea have been mixed. Studies using Lactobacillus species have shown very modest or no effect. Combination treatment with L. acidophilus, L. bulgaricus, B. bifidum, and S. thermophilus may be better for reducing the frequency of diarrhea, but there have been no head-to-head comparisons with single agents. S. boulardii also may modestly reduce traveler’sdiarrhea. Results of studies looking at probiotics for traveler’s diarrhea have been mixed. Studies using Lactobacillus species have shown very modest or no effect. Combination treatment with L. acidophilus, L. bulgaricus, B. bifidum, and S. thermophilus may be better for reducing the frequency of diarrhea, but there have been no head-to-head comparisons with single agents. S. boulardii also may modestly reduce traveler’sdiarrhea. 26

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Diarrhoea Other Probiotic Uses 28

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Diarrhoea SAFETY 31

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Diarrhoea SUMMARY 33

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