Diarrhoea 2 - Pharmacology Flashcards
Diarrhoea
• Diarrhoea can be good! Removes irritating substances for gut.
• May be due to underlying disease
• May lead to significant fluid & salt loss (reduced fluid
absorption) which can be lethal
Causes of acute diarrhoea
- infectious diarrhoea
- drug and alcohol use
- medical conditions
- other
Causes of chronic diarrhoea
- metabolic disease
- auto-immune disease
- functional
- cancer
- endocrine
- malabsorption
- medical intervention
- emotional
- constipation
Diarrhoea - Treatment
– Identify cause of diarrhoea
– restore fluids/electrolytes –oral re-hydration therapy
– elimination of infection may be necessary – absorbent agents eg kaolin (clay)
– anti-diarrhoeal drug
Antidiarrheal drugs are indicated in the following circumstances:
• Severe or prolonged diarrhea (>2 to 3 days), – to prevent severe fluid and electrolyte loss
• Severe diarrhea in young children and older adults. – less able to adapt to fluid and electrolyte losses.
• When specific causes of diarrhea have been determined
• In chronic inflammatory diseases of the bowel (ulcerative colitis and Crohn’s disease)
– to allow a more normal lifestyle
• In ileostomies (surgical excision of portions of the ileum)
– to decrease fluidity and volume of stool
Contraindications to the use of antidiarrheal drugs include diarrhoea caused by:
• toxic materials,
• microorganisms that penetrate intestinal mucosa (eg,
pathogenic E. coli, Salmonella, Shigella),
• or antibiotic-associated colitis.
- In these circumstances, antidiarrheal agents that slow peristalsis may aggravate and prolong diarrhea.
- Opiates (morphine, codeine) usually are contraindicated in chronic diarrhea because of possible opiate dependence.
- Difenoxin, diphenoxylate, and loperamide are contraindicated in children younger than 2 years of age.
Anti-Diarrheal Agents
-Anti-motility Agents
• Reduce peristalsis by stimulating opioid receptors in the bowel
• Decrease GI motility
• Increase absorption of water from the bowel
-Adsorbents and bulk-forming drugs
• Bulk forming agents can be useful in some forms of low- grade chronic diarrhoea
• Adsorbents such as Kaolin not recommended for acute diarrhoea
Anti-Dhiarrhoea Drugs 1 - Opioids
- Opioids continue to be used widely
- Mechanism of action: 1.Intestinal motility u receptors
- Intestinal secretion delta receptors
- Intestinal absorption u and delta receptors
• Commonly used opioids act via peripheral receptors
• Preferred over opioids that penetrate central nervous system
- loperamide is the strongest and widely used opioid anti-dhiarrhoeal drug
Loperamide (Imodium)
• 40-50 times more potent than morphine as an anti- diarrheal agent
– Increases small intestinal and mouth to cecum transit time; Increases anal sphincter tone; Anti-secretory activity against cholera toxin and some forms of E.coli toxin
– Effective in travellers diarrhea; Adjunctive treatment in almost all forms of chronic diarrheal diseases.
• Half- life 11 hours
• Dose: 4mg by mouth initially followed by 2mg after each
subsequent stool, up to 16mg/day.
• Lacks significant abuse potential as very little gets into brain
• ADR: Abdominal cramps; dizziness, drowsiness and urticaria
Codeine
-slow release pro drug of morphine
• Weak opiate
• 30 mg 3-4 times daily by mouth
• Duration of action 4-6 hrs; Action largely due to metabolism to morphine (which can get into brain)
• ADRs: drowsiness; long list of opioid-related minor side effects Can cause physical dependence
• Cautions: impaired respiratory function; driving
• CIs: Acute respiratory depression; paralytic ileus (low muscle tone in ileum)
Morphine
- Strong opiate
- Used as Kaolin and Morphine Mixture: 550- 800 mcg/10mL dose, once every 6 hours
- Sedation and risk of dependence greater than for codeine, but ADRs, cautions and CIs similar.
Co-Phenotrope
- Combination of diphenoxylate and atropine
- Diphenoxylate – opiate
- Atropine – antiperistaltic and ADR’s reduce abuse potential
- Opiate can cross BBB → can cause euphoria, respiratory depression, drowsiness, diziness
- Avoid in patients with acute inflammatory disease of bowel (ulcerative colitis, Crohn’s disease) – cause acute toxic megacolon
Adsorbents
• Non-selectively absorbs intestinal fluid – Regulates stool texture and viscosity
– Bind bacterial toxins and bile salts
• Kaolin
– 30-120mL 20% suspension after each loose stool
• Can bind other medications, must space out from others by 2 to 3 hours
Probiotics
replace normal microflora to restore intestinal function after use of antibiotic and by doing so suppresses overgrowth of pathogenic bacteria such as C.Diff
• Replaces normal colonic microflora
– Restores intestinal function and suppresses the growth of pathogenic bacteria
• Lactobacillus acidophilus (Lactinex®)
– 2 tabs or 1 packet of granules 3-4 times daily
given in diary form
• Dairy Products
– 200-400 grams of lactose
– Special ‘lactobacillus’ containing yogurts
Adsorbents
NOT RECOMMENDED FOR USE IN
ACUTE DIARRHOEA
