Antidiarrheals, Laxatives, and Analgesics

• Lecture covers antidiarrheal agents, laxatives, and analgesics.

Antidiarrheal Agents

• Antimotility agents like diphenoxylate and loperamide control diarrhea.
• Diphenoxylate and loperamide are analogs of meperidine and have opioid-like effects on the gut.
• These drugs should be avoided in young children or patients with severe colitis due to the risk of toxic megacolon.
• Bismuth subsalicylate is used for traveler's diarrhea by reducing fluid secretion in the bowel.

Laxatives

• Laxatives covered include irritants and stimulants, osmotic laxatives, saline and osmotic laxatives and electrolyte solutions

Irritants and Stimulants

• Senna is a natural anthraquinone glycoside complex that causes bowel evacuation in 8-10 hours when taken orally.
• Senna also causes water and electrolyte secretion into the bowel.
• Bisacodyl is available as suppositories and enteric-coated tablets.
• Bisacodyl stimulates the colon directly through nerve fibers in the mucosa.
• It is useful for opioid-induced constipation.

Osmotic Laxative: Lactulose

• Lactulose acts as an osmotic laxative as a sugar.
• Intestinal enzymes cannot hydrolyze it.
• Oral doses degrade in the colon via colonic bacteria into lactic, formic, and acetic acids.
• This degradation increases osmotic pressure, leading to fluid accumulation, colon distension, soft stools, and defecation.

Saline and Osmotic Laxatives

• Saline cathartics, like magnesium citrate and magnesium hydroxide, are non-absorbable salts that retain water in the intestine through osmosis.
• This process increases intestinal activity and induces defecation within a few hours.

Electrolyte Solutions

• Polyethylene glycol (PEG) are colonic lavage solutions for gut preparation before radiologic/endoscopic procedures.

Analgesics

• Prostaglandins sensitize nerve endings, transmitting pain signals to the brain and spinal cord.
• They also cause blood vessel dilation, resulting in inflammation-related redness.

Opioid Analgesics

• Opioid analgesics include: morphine, fentanyl, meperidine, propoxyphene, tramadol, methadone, and codeine.
• Partial agonist/antagonists include: pentazocin, buprenorphine, butorphanol, and nalbuphine.
• Dextromethorphan and codeine act as anti-tussives.
• Diphenoxylate and loperamide act as anti-diarrheals.
• They are used for analgesia for moderate to severe pain, cough suppression, antidiarrheal and controlling acute pulmonary edemas.
• Can also be used for anesthesia.
• Opioid use can lead to dependence with continued use of methadone or buprenorphine.

Side Effects of Opiods

• Sedation, increased intracranial pressure, nausea/vomiting, constipation, and miosis.

Withdrawal Symptoms of Opioids

• Rhinorrhea, nasal secretion, lacrimation, shivering, anxiety, diarrhea, muscle ache, and hypotension.

Non-Opioid Analgesics

• Non-steroidal anti-inflammatory drugs (NSAIDs) and Aspirin-like drugs have antipyretic analgesic qualities.

Non-Selective NSAIDs: Aspirin

• Aspirin is the prototype.
• Low doses of aspirin (<300mg/day) act as an antiplatelet.
• Moderate doses (300mg-2g/day) act as an analgesic.
• High doses (2-4g/day) act as an anti-inflammatory.