Drugs for Diarrhea

1. Oral Rehydration and Supportive Care

2. Antimotility Agents (Opioid Derivatives)

Loperamide (Imodium)

• Mechanism: Peripheral mu-opioid receptor (MOR) agonist; 40-50 times more potent than morphine as an antidiarrheal. Does NOT cross the blood-brain barrier, so no CNS side effects or addiction risk. Also increases anal sphincter tone and has antisecretory activity (against cholera toxin, some E. coli toxins)
• Dose: 4 mg initially, then 2 mg after each loose stool; max 16 mg/day in adults
• Uses: Acute nonbloody, nonfebrile diarrhea; traveler's diarrhea; chronic diarrhea (adjunct); IBD-associated diarrhea (with caution)
• Available OTC (capsule, liquid, chewable tablet); peak effect in 3-5 hours; t½ ~11 h
• Caution: Avoid in active colitis (risk of toxic megacolon). FDA black-box warning - exceeding recommended dose can cause cardiac arrhythmias (torsades de pointes, cardiac arrest). Not recommended in children under 2 years
• "Loperamide is arguably the best agent for acute, nonbloody, nonfebrile diarrhea" - Sleisenger and Fordtran's GI and Liver Disease

Diphenoxylate + Atropine (Lomotil)

• Mechanism: Phenylpiperidine opioid derivative (related to meperidine); combined with atropine in a subtherapeutic dose to discourage misuse
• Dose: 2 tablets initially, then 1 tablet every 3-4 h; max 20 mg/day (diphenoxylate)
• Schedule V controlled substance; peak plasma levels in 1-2 h; t½ ~12 h
• Active metabolite: Difenoxin (also available alone as Schedule IV/V)
• Less effective than loperamide overall; has some CNS penetration

Codeine

• An opioid with antidiarrheal properties, sometimes used as an alternative but has higher abuse potential and CNS effects.

3. Bismuth Subsalicylate (Pepto-Bismol)

• Has antimicrobial, antisecretory, and anti-inflammatory properties from its bismuth and salicylate components
• Reduces stool liquidity and frequency
• Useful for mild diarrhea and traveler's diarrhea prophylaxis/treatment
• Low incidence of side effects (black stool/tongue discoloration are cosmetic; tinnitus at high doses)
• Caution: avoid with aspirin (salicylate toxicity); not in children with viral illness (Reye's syndrome risk)

4. Antisecretory Agents

• Racecadotril (acetorphan): Enkephalinase inhibitor - reduces intestinal hypersecretion. Available in many countries (not the US); produces less constipation than loperamide; efficacious and safe in children with acute diarrhea
• Octreotide: Somatostatin analogue used for secretory diarrhea, VIPoma-associated diarrhea, carcinoid syndrome, and post-surgical/dumping syndrome diarrhea

5. Adsorbents (Weak Evidence)

• Kaolin, pectin, activated charcoal: Decrease stool liquidity but do NOT reduce intestinal fluid loss or number of bowel movements. Limited clinical benefit.
• Anticholinergic agents (dicyclomine, hyoscyamine) may relieve cramping but do not alter diarrhea significantly.

6. Antibiotics (Specific Infectious Causes)

7. Probiotics

• Some evidence of benefit in reducing duration of diarrhea; commonly used in IBS-associated diarrhea. Evidence varies by strain.

Quick Summary by Setting

Drugs for Vomiting (Antiemetics)

1. Serotonin (5-HT3) Receptor Antagonists - FIRST LINE

• Mechanism: Block 5-HT3 receptors at the CTZ and vagal terminals in the GI tract
• Uses: Undifferentiated vomiting, chemotherapy-induced nausea/vomiting (CINV), post-operative nausea/vomiting (PONV), gastroenteritis (children)
• Adverse effects: Headache, dizziness, QT prolongation (mild)
• "Ondansetron is the first-line antiemetic due to its low side effect profile" - Rosen's Emergency Medicine
• Pediatrics: Ondansetron 0.15 mg/kg IV or PO is the first-line agent for vomiting in children with acute gastroenteritis; shown to reduce need for IV hydration and hospitalization

2. Dopamine (D2) Antagonists - Prokinetics

Metoclopramide (Reglan)

• Mechanism: Blocks D2 and 5-HT3 receptors at CTZ; also D2 in stomach and lower esophageal sphincter (prokinetic effect)
• Dose: 10-20 mg IV/IM, may repeat every 6 hours
• Uses: Undifferentiated vomiting, gastroparesis, dysmotility, hyperemesis gravidarum (drug of choice in pregnancy-associated vomiting)
• Adverse effects: Dystonic reactions, tardive dyskinesia (FDA black-box warning with prolonged use), neuroleptic malignant syndrome, akathisia
• First-line in the emergency department (second to ondansetron)

3. Phenothiazines (Dopamine Antagonists)

• Mechanism: Block D1/D2 receptors at CTZ; promethazine also has H1 antihistamine activity
• Uses: General-purpose antiemetics; considered third-line in the ED due to side effects
• Adverse effects: Sedation, extrapyramidal effects (dystonia, akathisia), hypotension, QT prolongation
• Warning: Promethazine IV extravasation can cause severe tissue necrosis - deep IM injection is preferred; if IV given, must dilute in 10-20 mL saline and infuse over 10-15 minutes

4. Butyrophenones (Dopamine Antagonists)

5. NK1 (Neurokinin-1) Receptor Antagonists

• Mechanism: Block substance P (NK1) receptors in the area postrema/CNS
• Combined with a 5-HT3 antagonist + dexamethasone: prevents acute emesis in 80-90% of patients on highly emetogenic chemotherapy
• Adding olanzapine 10 mg (days 1-4) further reduces CINV by 15-30%
• Metabolized by CYP3A4 - drug interactions with many chemotherapy agents

6. Corticosteroids

• Dexamethasone: 8-20 mg IV before chemotherapy, then 8 mg/day for 2-4 days
• Mechanism unknown, but potentiates 5-HT3 antagonists for both acute and delayed CINV
• Adjunct, not used alone

7. Antihistamines (H1 Antagonists)

• Act on H1 receptors in CTZ and vestibular pathways
• Sedating; do not combine with promethazine due to additive sedation

8. Anticholinergics

• Scopolamine (transdermal patch): Best for motion sickness; acts on muscarinic receptors in the vomiting center and vestibular system
• Adverse effects: dry mouth, blurred vision, urinary retention, sedation

9. Special Situations

ED Stepwise Approach (Adults)

1. Ondansetron 4 mg IV (first-line) + IV fluids if severe
2. Metoclopramide 10-20 mg IV/IM (if ondansetron fails)
3. Droperidol 1.25 mg IV or haloperidol 5 mg IV (after ECG to check QT)
4. Prochlorperazine 10 mg IV or promethazine 12.5 mg IM/IV (third-line)
5. Consider hospitalization if unresponsive to escalating therapy