Antidiarrheals Notes

NOTES NOTES ANTIDIARRHEALS GENERALLY, WHAT ARE THEY? Basic information ▪ Medications used to treat mild to moderate diarrhea Key points ▪ Diarrhea: defined as stool that contains fluid weight over 200g of fluid per day ▪ Should not be used in individuals with severe illness, bloody diarrhea, high fever ▫ Can mask/exacerbate underlying conditions ADSORBENTS Figure 1.1 Adsorbents: mechanism of action. WHAT ARE THEY? Mechanism of action ▪ Bismuth subsalicylate: antisecretory, antiinflammatory, antimicrobial effects ▪ Cholestyramine: binds to bile acids in intestine → forms nonabsorbable, insoluble complex with bile acids → ↓ electrolyte and water secretion; ↑ excretion of bile acids in feces → ↓ number of stools ▪ Kaolin + pectin: bind bacterial toxins and water → stool-bulking → ↓ stool fluidity OSMOSIS.ORG 1

TYPES ▪ Bismuth subsalicylate (Pepto-Bismol): PO ▪ Cholestyramine (Questran): PO ▪ Kaolin + pectin: PO Common indications ▪ Diarrhea Drug-specific indications ▪ Bismuth subsalicylate: traveler’s diarrhea treatment/prevention; dyspepsia, eradication of H. pylori (combined with metronidazole tetracycline—BMT regimen) ▪ Cholestyramine: bile acid diarrhea (people with bile acid malabsorption) CLINICAL CONCERNS ADVERSE EFFECTS Drug-specific adverse effects ▪ Bismuth subsalicylate ▫ Bismuth: black tongue/stool discoloration ▫ Salicylate: ototoxicity (hearing loss, tinnitus); Reye’s syndrome (post-viral children) ▪ Cholestyramine ▫ Teeth discoloration, erosion ▫ Gastrointestinal (GI): abdominal pain, anorexia, nausea, flatulence ▫ Fat-soluble vitamin malabsorption (vitamins A, D, E, K) ▪ Kaolin + pectin ▫ Constipation ADMINISTRATION ▪ Cholestyramine ▫ Holding liquid in mouth can damage teeth ▫ Take other medications, fat-soluble vitamins at least 4hrs before cholestyramine ▪ Kaolin + pectin ▫ Avoid concomitant use with other medications ( associated with ↓ intestinal absorption) 2 OSMOSIS.ORG Dietary ▪ Cholestyramine ▫ Supplementation with fat-soluble vitamins may be required

Gastrointestinal Antidiarrheals Figure 1.2 Adsorbents: common drug-drug interactions. Figure 1.3 Adsorbents: general adult dosing guidelines. *Dose and dosing interval varies depending on individual characteristics OSMOSIS.ORG 3

OPIOIDS Figure 1.4 Opioids: mechanism of action. WHAT ARE THEY? Mechanism of action ▪ Stimulate μ/δ opioid receptors in enteric nervous system, intestinal smooth muscle → ↓ peristalsis → ↓ stool frequency ▫ Loperamide: antisecretory effect TYPES ▪ Diphenoxylate (Lomotil): PO ▫ High addictive potential; preparations contain subtherapeutic atropine dose (anticholinergic) → discourages abuse; works synergistically to ↓ intestinal motility ▪ Loperamide (Imodium): PO ▫ Low addictive potential (poor CNS penetration) Common indications ▪ Diarrhea 4 OSMOSIS.ORG Drug-specific indications ▪ Loperamide: chronic diarrhea; first-line treatment for traveler’s diarrhea CLINICAL CONCERNS ADVERSE EFFECTS ▪ Constipation, abdominal cramps; drowsiness, dizziness; paralytic ileus Drug-specific adverse effects ▪ Diphenoxylate ▫ Anticholinergic side effects due to atropine component (e.g. dry mouth, blurred vision, sedation, hyperthermia, urinary retention) ▪ Loperamide ▫ Boxed warning: torsades de pointes, cardiac arrest (at higher than recommended dose)

Gastrointestinal Antidiarrheals DISEASE-RELATED CONCERNS ▪ Diphenoxylate ▫ Hepatic/renal impairment: may precipitate hepatic coma ▫ Ulcerative colitis: may induce toxic megacolon ▪ Loperamide ▫ Ulcerative colitis: may induce toxic megacolon ▪ Avoid concomitant use with other CNS depressants (e.g. benzodiazepines, barbiturates) CONTRAINDICATIONS ▪ Children below the age of 4 ( ↑ risk of CNS depression) ▪ Loperamide ▫ Individuals with QT-prolongation Dietary ▪ Alcohol: ↑ risk of CNS depression Figure 1.5 Opioids: common drug-drug interactions. OSMOSIS.ORG 5

Figure 1.6 Pharmacokinetic interactions: Opioids. Figure 1.7 Opioids: general adult dosing guidelines. *Dose and dosing interval varies depending on individual characteristics 6 OSMOSIS.ORG