Definition

Diarrhea is a condition characterized by an increased frequency of passing stool, typically three or more times a day, accompanied by a change in stool consistency to a more liquid form. Drug-induced diarrhea occurs after consuming certain medications. The heightened frequency of diarrhea is often attributed to the intestine being the primary absorption site for ingested medications. Many drugs can have side effects that disrupt fluid absorption in the gastrointestinal tract, particularly in the small and large intestines. Common side effects of drugs include heartburn, nausea, vomiting, diarrhea, and constipation.

Based on the onset of diarrhea it can be classified into two categories: acute diarrhea, which occurs a few days after taking medications, and chronic diarrhea, which manifests after two weeks of medication consumption.

Causes

More than 700 drugs have been identified as potential causes of diarrhea. However, the mechanisms underlying the diarrhea-inducing effects of these drugs are not always well understood. These drugs can impact the regulation of the gastrointestinal system, leading to diarrhea. The effect may be a direct consequence of the drug itself or arise from disruptions caused by the drug within the gastrointestinal tract.

Some known mechanisms that can cause drug-induced diarrhea, which may co-occur, include:

• The consumption of solutions that are difficult to digest or have a high concentration of dissolved substances. Examples include mannitol, sorbitol, lactulose, or magnesium, found in laxatives and antacids for treating stomach symptoms
• Increased fluid and ion output in the gastrointestinal tract
• Disruption of fluid absorption in the tissues of the gastrointestinal tract
• Motility problems in the gastrointestinal tract
• Release of blood, mucus, and proteins into the gastrointestinal tract due to inflammation or injury in the gastrointestinal tract
• Disorders in fat and carbohydrate metabolism and absorption

Some medications that can cause diarrhea include:

• Antibiotics: Penicillin, Cephalosporin, Clindamycin, Quinolone, Macrolide, etc. In normal conditions, the intestine harbors many bacteria that maintain the balance of intestinal flora. Antibiotic use can eliminate these bacteria, allowing other bacteria to grow rapidly. Clostridium difficile is a bacteria that can cause diarrhea due to antibiotic use. Antibiotic-induced diarrhea typically starts soon after drug consumption, is mild, and gets better after discontinuation.
• Laxatives work by absorbing water into the intestine or increasing intestinal contractions
• Stomach medications like antacids containing Magnesium or Calcium, Lansoprazole, Esomeprazole, Omeprazole, Pantoprazole, and Rabeprazole
• Selective serotonin reuptake inhibitor (SSRI) type antidepressants: Citalopram, Escitalopram, Fluoxetine, Sertraline, and Paroxetine
• Diabetes mellitus drugs: Acarbose can disrupt glucose absorption in the gastrointestinal tract, leading to diarrhea. Metformin, Liraglutide
• Cancer medications: Methotrexate, Cyclophosphamide, Doxorubicin, etc. These drugs can disrupt food digestion and small intestine function, leading to diarrhea.
• Antihypertensive drugs: Captopril, Lisinopril
• Cholinergic drugs: Neostigmine, Pyridostigmine, Edrophonium, Rivastigmine, and Donepezil
• Immunosuppressant drugs: Mycophenolate mofetil (commonly used by transplant recipients), Tacrolimus, Ciclosporin, and Corticosteroids
• Anti-inflammatory drugs (NSAIDs): Mefenamic acid, Sodium diclofenac, Piroxicam, Meloxicam, and others
• Other drugs: Colchicine (for gout patients), Diacerein, Antiretroviral drugs, Misoprostol, Cisapride, Digoxin, Metoclopramide, Orlistat, and Sildenafil

Risk Factor

Drug-induced diarrhea can occur in all people who consume medication. However, someone is more at risk of experiencing drug-induced diarrhea if they: 

• Have a history of drug-induced diarrhea
• Consuming medication for a long period
• If you are using multiple drugs, determining or identifying the exact drug that is causing diarrhea can be more challenging.

Symptoms

Symptoms of drug-induced diarrhea include:

• Increased frequency of passing stool, typically 3 or more times a day or more than 250 g of feces daily
• Changes in feces consistency, becoming more watery
• Antibiotic-induced diarrhea: When Clostridioides difficile growth occurs, diarrhea can be more severe and may be associated with blood and mucus. Other symptoms may include low fever, nausea, and a reduced appetite.
• Fatty diarrhea
• Abdominal cramps
• Dehydration is due to a lack of fluids, manifesting as signs of thirstiness, paleness, and dry lips. Severe dehydration signs include a parched mouth, excessive thirst, reduced frequency and quantity of urine, a feeling of lightheadedness, weakness, and reduced consciousness.
• Weight loss due to fluid and nutrition loss

Diagnosis

Drug-induced diarrhea is suspected if there is a period between medication consumption and the onset of diarrhea. It is diagnosed if diarrhea occurs not long after consuming a particular medication (within 6-8 weeks) and if diarrhea reduces or stops after discontinuation. However, examinations need to be conducted to exclude other causes of diarrhea, such as blood tests or fecal tests. Additional examinations, like endoscopy or radiology tests, are recommended for indications or suspected complications.

Management

In some cases, diarrhea may resolve spontaneously while continuing the medication due to the adaptation of the gastrointestinal tract. However, this is not universally applicable, and the most straightforward approach to managing drug-induced diarrhea is to discontinue the causative drug and switch to an alternative medication. If discontinuation is not feasible, reducing the dosage of the implicated drug may be considered. Typically, symptoms improve within a few days after making these adjustments.

Drugs that stop diarrhea, like loperamide, bismuth subsalicylate, and kaolin-pectin, can be taken to make symptoms go away faster. However, it is essential to note that loperamide is not recommended for severe diarrhea. In cases of severe diarrhea, loperamide may impede the elimination of bacteria and toxins, potentially causing further complications.

In addition to antidiarrheal drugs, probiotics can be used to restore the normal flora of the intestine. Doctors may prescribe antibiotics that specifically target Clostridioides difficile (C. difficile) in cases of diarrhea. It's important to note that there are no specific drugs explicitly designed for the treatment of drug-induced diarrhea.

Complications

Drug-induced diarrhea seldom causes severe complications if handled correctly. However, in some cases, diarrhea can be severe and lead to complications such as:

• Damage to the mucous layer of the gastrointestinal tract results in a slower healing period. For example, antibiotic-induced diarrhea can cause inflammation in the large intestine, a condition known as pseudomembranous colitis. This condition can be detected through endoscopy and biopsy examinations
• Severe dehydration, if not appropriately managed, can lead to unconsciousness and, in extreme cases, death
• An ion imbalance can result in an irregular heartbeat

Prevention

Some preventive measures for drug-induced diarrhea include:

• Consider probiotic consumption, as some studies suggest it can be helpful for therapy and prevention of diarrhea, especially when induced by antibiotics
• Avoid drugs or medications known to induce diarrhea. If possible, explore alternative medications
• Consult with a doctor or physician before consuming drugs, and only use medication if necessary

When to See a Doctor?

If you experience severe and prolonged diarrhea, especially if accompanied by fever and weight loss, it is recommended to consult with a doctor or physician. They can provide appropriate management and conduct examinations, such as fluid therapy, electrolytes, and the right nutritional supplements. If the suspected drug causing diarrhea cannot be stopped, it is advisable to consult with the doctor for further guidance on management.

Want to know more information about other diseases? Click here!