33. Laxatives, antidiarrhoeal agents, drug treatment of inflammatory bowel disease and paralytic ileus, digestives, drugs used in cholelithiasis

Last updated on June 21, 2019 at 16:03

Introduction to laxatives

These drugs stimulate the transit of food through the intestine. The user should always ensure sufficient fluid and electrolyte intake when using any of these. Overuse can lead to an atonic colon where the natural peristaltic activity is diminished.

Indications:

  • Obstipation
  • Enteritis – to remove toxins or infective agents
  • Colon cleansing before surgery, endoscopy or radiological examination

Classification:

We differentiate four different types of laxatives:

  • Bulk laxatives – compounds that are not digested and therefore form a bulky faecal mass, which promotes peristalsis
  • Osmotic laxatives – osmotically active compounds that are not absorbed, which will trap fluid in the lumen
  • Faecal softeners – compounds that soften the stool
  • Stimulant laxatives – drugs that increase water secretion by the mucosa and stimulate peristalsis
Bulk laxatives

The most important bulk laxatives are dietary fibres containing lignin or cellulose, semisynthetic compounds like methylcellulose or agar.

Mechanism of action:

These compounds are non-digestible, so they will add bulk to the stool. The increased bulk promotes peristalsis.

Osmotic laxatives

The most important osmotic laxatives are:

  • Non-absorbable salts like sodium phosphates and certain magnesium salts
  • Non-absorbable carbohydrates like lactulose
  • Macrogols

Mechanism of action:

Sodium sulphate, certain magnesium salts and lactulose are poorly absorbed but osmotically active, so they will trap water in the lumen.

Macrogols are comprised of polyethylene glycol, which is osmotically active and not absorbable.

Faecal softeners

The most important faecal softeners are docusate (Klyx) and liquid paraffin.

Mechanism of action:

These compounds emulsify and soften the stool.

Dosing:

These compounds are given rectally as an enema.

Stimulant laxatives

The important stimulant laxatives are bisacodyl (Dulcolax) and Senna glycosides.

Mechanism of action:

Senna glycosides stimulate the myenteric plexus, resulting in increased peristalsis.

Bisacodyl also stimulates the myenteric plexus, but it also stimulates water secretion from the mucosa.

Dosing:

Senna is taken orally. Bisacodyl can be taken orally or as a suppository.

Antidiarrhoeal agents

Diarrhoea is defined as abnormally increased frequency or quantity of stools. Depending on the etiology of the diarrhoea, anti-infective agents may be necessary. Diarrhoea should always be treated with maintained fluid and electrolyte balance.

Most cases of diarrhoea are self-limiting and don’t require pharmacological treatment.

The most important drugs here are:

  • Antimotility agents – drugs that inhibit the peristaltic activity
  • Adsorbents – drugs that adsorb microorganisms and toxins
  • Dietary fibres – which absorb water
Antimotility agents

The important drugs here are loperamide, diphenoxylate, mebeverine and anticholinergic agents.

Mechanism of action:

Loperamide and diphenoxylate are peripherally acting opioids.

Mebeverine has direct inhibitory effects on the smooth muscle in the colon.

Anticholinergic agents reduce gastric motility.

Inflammatory bowel diseases

In the treatment of inflammatory bowel diseases, many drug types are used:

  • Corticosteroids
    • Prednisolone
  • Immunosuppressants
    • Azathioprine
    • Mercaptopurine
    • Methotrexate
  • 5-ASA drugs
    • Mesalazine
    • Sulphasalazine
  • Immune therapy (antibodies against TNF-α)
    • Infliximab
    • Adalimumab

Mesalazine and sulphasalazine are salicylates that are designed to be released locally in the GI rather than to be absorbed. They’re only effective in ulcerative colitis and not in Crohn disease.

Indications:

Corticosteroids are only used to treat acute episodes. The other drugs are used for maintenance of remission.

Mechanism of action:

These drugs are anti-inflammatory and decrease the inflammatory component of IBD.

The active compound of mesalazine and sulphasalazine is 5-aminosalicylic acid or 5-ASA (not acetylsalicylic acid, which is aspirin). 5-ASA, like aspirin, inhibits COX.

Cholelithiasis

Two drugs are important in the treatment of cholelithiasis and biliary colic; ursodeoxycholic acid, and buprenorphine.

Indications:

Ursodeoxycholic acid can dissolve cholesterol stones.

Buprenorphine is used to provide analgesia for biliary colic.

Mechanism of action:

Ursodeoxycholic acid inhibits the synthesis of cholesterol, thereby decreasing the amount of cholesterol in the bile. In the long run this may cause the cholesterol stone to dissolve.

Buprenorphine is an opioid which has µ agonist and κ and δ antagonist effects. This gives opioid-like analgesia but doesn’t cause the opioid-induced constriction of the sphincter of Oddi.

Pancreatic enzyme supplementation

In chronic pancreatitis there is a deficiency of pancreatic enzymes, causing maldigestion and malabsorption. Pancreatic enzymes can be supplemented. Pancreatin and pancrelipase are commercial preparations of pancreatic enzymes designed to be released from their capsule when it reaches the duodenum. They should be taken with every meal.

Hepatic encephalopathy

Hepatic encephalopathy is caused by excessive amounts of ammonia (NH3) in the CNS. Treatment involves decreasing the production of ammonia by enteric bacteria. For this, several drugs can be useful:

  • Lactulose
  • Broad-spectrum non-absorbable antibiotics (neomycin, rifaximin)

Dietary protein restriction is mentioned on the lecture however this should only be used as a temporary measure. Long-term protein restriction increases protein catabolism, which increases endogenous ammonia production. Also, people with hepatic encephalopathy have cirrhosis and therefore have a high demand for proteins. Protein restriction in patients with cirrhosis can cause malnutrition and increased mortality.

Mechanism of action:

Lactulose decreases the pH of the gastrointestinal lumen. This causes ammonia (NH3) to be converted to its corresponding base, ammonium (NH4+). This compound is less absorbed and less toxic.

Non-absorbable antibiotics can decrease the ammonia-producing bacterial flora in the gastrointestinal tract.


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