ANTI-DIARRHEA
NON-SPECIFIC THERAPY
Oral and Parenteral rehydration
Oral rehydration solution (ORS)
→ Balanced mixture of glucose and electrolytes
● Sip with food
Mechanism:
● Glucose and Na+ absorption is linked with water uptake.
● Matched glucose and Na+ volume prevents dehydration.
Limitations:
● Does not reduce stool volume
● Low efficacy in: shock, severe emesis, high stool output
Ringer’s Lactate Solution (RL)
→ ​Mixture of NaCl, sodium lactate, KCl, CaCl2 in
water
● Replaces fluids and electrolytes
● Injection
Sfx:
● Infection at injection site
● Venous thrombosis
● Hypervolemia
Anti-motility and antisecretory agents
Opioids
● Acts on opioid receptors (at CNS, PNS, GI)
○ Reduces ​GI motility
● Morphine-like effects → pain relief, diarrhea suppression
○ ↑ segmentation and ↓ propulsive movement →
increased time for absorption
○ Antisecretory
○ ↑ Internal anal sphincter tone and ↓ respose to full
rectum stimulus
Loperamide (Imodium)
● MOR activity
● Does ​NOT​ cross BBB → x addiction
● Slows gut motility, negligible CNS effects
Tx:
● Specific + non-specific diarrhea
● Acute + chronic + traveller’s diarrhea
ADR:
● Abdominal pain, constipation, hypersensitivity, N/V
● OD → crosses BBB → CNS depression, paralytic ileus
Diphenoxylate
● Anti-diarrheal effect
● No analgesic property
● Higher doses → CNS effects
● Long-term → ​opioid dependence
Atropine
● Combined to discourage OD, but acts on anticholinergic
receptors to case sfx
Sfx: ​Dry mouth, blurred vision, urinary retention, bradycardia
Somatostatin
→ ​14 amino acid peptide released in GI, pancreas
and hypothalamus
● Inhibits hormone secretion
● ↓ intestinal secretion
● ↓ GI motility
⇒ ​Limited by short half-life (3 mins)
Octreotide
→ ​synthetic octapeptide, similar action to
somatostatin
● Longer half-life (1.5 hour IV, 6-12 hour SC)
Octreotide and somatostatin
→ ​Reduces secretion
● Symptomatic Tx of carcinoid tumor + peptide
secreting tumors
ADR:
● Steatorrhea​ → fat in stool
● Nausea, abdominal pain ,flatulence,
diarrhea, hyperglycemia, bradycardia
Adsorbents
● Coats GI walls
● Binds to agent/toxin → elimination in stool
Kaolin-Pectin
→ Combined hydrated MgAl silicate + indigestible carbohydrate
● Adsorbs bacterial toxin
● Tx: acute diarrhea
● ADR: none
Activated Charcoal
→ Black, odorless power (tasteless, nontoxic)
● Adsorbs chemicals → ↓ toxicity
● Excreted in feces
Bismuth subsalicylate (Pepto-Bismol)
→ Hydrolyzes to ​bismuth oxychloride and salicylic acid
● Anti-secretory, anti-inflammatory, antimicrobial effects
○ Stimulates fluid absorption
○ Inhibits prostaglandins
Sfx: ​dark stool, black staining tongue
● N/V, tachycardia
● Salicylism if taken > 6 weeks (salicylic acid toxicity)
Bile salt-binding resins
Cholestyramine
Colestipol
Colesevelam
● Binds bile salts that cause diarrhea from
malabsorption
Sfx:
● Bloating, flatulence, constipation, fecal
impaction
ADR:
● Cholestyramine and colestipol reduces drug
and fat absorption​ so should be used spaced
out from other drugs and may cause
fat-soluble vitamin deficiency.
SPECIFIC THERAPY
Antimicrobial agents
Ciprofloxacin, Levofloxacin, Azithromycin, Rifaximin
● Eradicates bacteria
● Stops multiplication by inhibiting reproduction and repair of genetic material
● Tx: traveller’s diarrhea
LAXATIVES
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Soften stool
Reduces intestinal transit time to stimulate defecation
Tx: constipation, cleaning colon before surgery, eliminate toxic substances
Bulk-forming laxatives
Psyllium hydrophilic mucilloid, dietary fiber
→ Fibers, resist enzymatic digestion
● Increases amount of water in stool → bulkier, softer,
hydrated stool
● ↑ water in lumen → ↑ mass → ↑ intestinal surface
distension → ↑ intestinal movement
● Take with a lot of water
● Slow onset
Tx: ​constipation, diarrhea (absorbs water to
increase bulk → decreasing watery stool)
Sfx: ​safest, most effective LONG TERM
● Flatulence, abdominal cramping
Surfactant laxatives
Docusate sodium, docusate calcium
→ ​Stool softeners/emollient agents
● Reduces surface tension to enhance water and fat
incorporation into stool
Tx:
● Constipation + ​hemorrhoids
● Post-op: reduce straining with defecation
Osmotic laxatives
MOM, Lactulose, Glycerin (rectal), PEG
→ Osmolar sugars
● ↑ water in intestinal lumen by osmosis → soften stool
● ↑ intestinal tone → ↑ peristalsis
Tx:
● Colon cleaning before surgery (PEG)
● Constipation + hepatic encephalopathy (Lactulose)
● SHORT TERM only
CI: ​Renal disorders → ↑ electrolyte imbalance
Lubricant laxatives
Mineral oil
● Coats stool with oil → ↓ water reabsorption →
softened, more easily expelled
Tx: ​Constipation
ADR
● Lung aspiration (children/elderly)
● Reduced absorption of fat-soluble vitamins
Stimulatory laxatives
Bisacodyl, castor oil, senna
● Irritates smooth muscle of intestine to stimulate
prostaglandins → increased water excretion and
reduced water absorption
● FAST ACTION
● Low-grade inflammation
Tx:
● Short-term constipation
● Colon cleaning
Sfx:
● Abdominal cramping
● Electrolyte loss
● Uterine contraction in pregnancy → x
pregnancy/breastfeeding
Chloride channel activators
Lubiprostone
→ Prescription drug
● Prostanoid activator → secretion of Cl- rich fluid →
improves stool consistency and increases intestinal
motility
Tx:
● Severe chronic idiopathic constipation in adults (stool
softeners do not work :()
● IBS-C dominant
Sfx:
● GI disturbances
CI:
● Pregnancy
● Children
Opioid receptor antagonists
Methylnaltrexone (SC), Alvimopan (PO)
● Peripherally selective Opioid μ-receptor antagonists
● Does not cross BBB ⇒ no CNS effects
● Specifically targets opioid induced constipation
Tx:
● Methylnaltrexone (SC) → palliative care
● Alvimopan (PO) → constipation after surgery (short-term)
Sfx:
● Methylnaltrexone (SC) → GI disturbances, pain
● Alvimopan (PO) → hypokalemia, dyspepsia, urinary retention, back pain
Irritable Bowel Syndrome
IBS-D
Non-pharmacological methods
● Reduce avoidance behavior
○ Regular meals, sufficient fluids, exercise
○ CBT, behavior, hypnosis → reduce stress
● Dietary modification
○ Avoid trigger foods
○ Low FODMAP diet → poorly absorbed short
chain FAs
○ Fiber supplements
Antidiarrheal medication
Loperamide (Imodium)
● 1st line
● Better safety profile as if does not cross BBB
● Tx: painless IBS-D
● Reduces stool frequency and urgency
Cholestyramine
● Tx: post-cholecystectomy IBS
IBS-C
Non-pharmacological methods
● Lifestyle
○ Increase dietary fruits and vegetables
○ Exercise
○ Fluid intake
● Fiber supplementation
○ Natural fibers
Laxative agents
Bulk-forming laxatives
● Synthetic or natural fibers
● Softens stool to reduce straining
● Does ​not​ improve pain/bloating
● ADR: ​flatulence, gas
● Safest, most effective, LONG-TERM :)
Osmotic laxatives
● Absorbs water in intestine by osmosis
Chloride channel activators
● Softens stool
● Increases intestinal motility
Secretory laxatives
● Not recommended for long-term use
● Not for IBS-C
IBS-pain
Antispasmodic medications
● Use as needed
● May worsen constipation → ​IBS-D
● Reduce muscle spasm and abdominal pain/cramping
1. Autonomic innervation
→ Anticholinergic agents
Dicyclomine, hyoscyamine, atropine
● Competitive antagonist of​ ACh at muscarinic receptor
→ ↓ motility and secretion → constipation
● ADR: ​blurry vision, constipation, urinary retention
● CI: ​glaucoma
2. Smooth muscle function
Mebeverine
● Direct effect on colonic muscle
● No antimuscarinic activity
Alverine
● Ion channel inhibitor → smooth muscle relaxation
● ADR:​ ​hypersensitivity/rash
Antidepressants
● Analgesic properties
● Low dose → relieves diarrhea, pain, cramping
● High dose → relieves depression + anxiety
→ Tricyclic Antidepressants (TCAs)
Imipramine, Amitriptyline
● Inhibits 5-HT serotonin and NE uptake → improves
mood
● Antimuscarinic receptors → Anticholinergic effect ⇒ ↓
GI motility
● CI: ​glaucoma, constipation
● ADR: ​blurry vision, urinary retention, constipation
Tx: ​low doses for chronic abdominal pain,
● No mood effect
● Sedative → take before bed
● Anticholinergic properties
Serotonin receptor altering
Serotonin 5-HT3 receptor antagonist
Tryptophan
● Regulates GI function, mood, appetite
● Blocks unpleasant visceral sensation, central response and GI motility →​ IBS-D
Alosetron
● Highly potent
● Reduces sensitivity and activity of colon
● Tx: ​severe IBS-D
● ADR: ​constipation,​ ischemic colitis
Serotonin 5-HT4 receptor agonist
Tegaserod, Prucalopride, Renzapride
● Stimulates receptors → ↑ intestinal secretion, peristalsis, bowel transit → ↑ stool liquidity
● Tx: ​short term IBS-C
● Tegaserod: ​removed from market due to CVD risk
● ADR: ​CVD, heart attack, angina, stroke