Table of Contents
Page created on June 14, 2019. Last updated on January 7, 2022 at 22:23
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:
- Macrogols
- Non-absorbable salts like sodium phosphates and certain magnesium salts
- Non-absorbable carbohydrates like lactulose and sorbitol
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
Compounds:
- Opioids
- Loperamide (most important)
- Diphenoxylate
- Mebeverine
- Anticholinergics
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
- Budesonide (topical)
- Prednisolone (systemic)
- Immunosuppressants
- Azathioprine
- Mercaptopurine
- Methotrexate
- 5-ASA drugs
- Mesalazine
- Sulphasalazine
- Biological therapy (antibodies against TNF-α)
- Infliximab
- Adalimumab
Indications:
Corticosteroids are only used to treat acute episodes. The other drugs are used for maintenance of remission.
Administration:
5-ASA drugs can be taken orally or rectally as suppositories or enemas.
Budesonide is taken orally but is not absorbed and instead acts locally in the GI tract.
The antibodies are given as subcutaneous injections every 2 weeks.
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). The mechanism of action of 5-ASA is not well known. They probably act locally. Possible mechanisms include inhibition of cytokine synthesis, inhibition of COX and lipoxygenase, immunosuppression, etc.
Cholelithiasis
Compounds:
- Litholytics
- Ursodeoxycholic acid
- Analgesics
- NSAIDs
- Opioids
- 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. The therapy takes at least 6 months.
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.