Loperamide is a drug that belongs to the opioid class of drugs and is used to treat diarrhea. It is on the WHO (World Health Organization) list of essential medicines.
What is loperamide?
Loperamide is a drug that belongs to the opioid class of drugs and is used to treat diarrhea. The drug loperamide was first synthesized by Paul Janssen for the company Janssen Pharmaceutica. From a chemical point of view, loperamide is a diphenyl-piperidine. It belongs to the group of pseudopioids. The first clinical study with the active ingredient appeared in an American journal in 1973. In the same year, loperamide was launched on the market and is still available under the trade name Imodium. Loperamide has also been available on the German market since 1976. In Germany, it is the most frequently sold, non-prescription medication for diarrhea. It is recommended for the symptomatic treatment of acute diarrhea. The drug is administered orally and is also contained in some combination preparations together with the active ingredient simeticon. In all available forms, loperamide is available only through pharmacies.
Pharmacologic action
Loperamide hydrochloride binds to µ-opioid receptors in the myenteric plexus. The myenteric plexus, also known as Auerbach’s plexus, traverses almost the entire musculature of the gastrointestinal tract. It is part of the enteric nervous system (ENS) and regulates peristalsis of the intestine. It also regulates the secretion of digestive enzymes into the intestine. Via the µ-opioid receptors, loperamide reduces intestinal smooth muscle activity. In particular, the longitudinal and circular muscles of the small intestine are inhibited in their activity. Due to the weakened peristalsis, the intestinal contents remain longer in the small intestine. The intestinal contents are thus in contact with the mucosa of the small intestine for a longer period of time, so that electrolytes and fluids can be absorbed more. The stool becomes more solid. In addition, loperamide increases the muscle tension of the anal sphincter. This results in improved fecal continence. Since loperamide cannot cross the blood–brain barrier, it does not reach the opioid receptors and is therefore classified as a sham opioid. Loperamide is effective only locally.
Medical application and use
The main indications for the use of loperamide are diarrhea of any type. The drug is taken orally for traveler’s diarrhea, nonspecific diarrhea, diarrhea associated with irritable bowel syndrome, or diarrhea resulting from intestinal peristaltic disorders. Under medical supervision, loperamide is also used to treat diarrhea caused by cytostatic drugs or so-called protease inhibitors as part of chemotherapeutic treatment. In combination with the active ingredient simeticon, loperamide is administered for acute diarrhea with abdominal cramps.
Risks and side effects
It should be noted that loperamide is only symptomatic and therefore does not address the cause of the diarrhea. While it can help stop the loss of fluids and electrolytes, it should still only be taken for a short time if there is a known underlying condition or in parallel with causative therapy. Loperamide is not suitable for the treatment of infectious diarrheal diseases. These are usually manifested by mucus, blood or pus in the stool. Loperamide immobilizes the intestines and prolongs intestinal transit. This effect is desirable in some diarrheal diseases, but in infectious dysenteries it prolongs the residence time of the pathogens in the intestine. While the pathogens remain in the intestine, they can continue to release toxins into the intestine. This can be particularly dangerous in the case of infection with enterohemorrhagic E. coli (EHEC). The toxins can cause hemolytic uremic syndrome (HUS). Loperamide should also not be used in acute episodes of the chronic inflammatory bowel disease ulcerative colitis. Other contraindications include pseudomembranous colitis, use of broad-spectrum antibiotics, and any condition in which intestinal peristalsis is pathologically inhibited. These include intestinal obstruction (ileus), megacolon, and toxic megacolon. In general, loperamide is very well tolerated. However, abdominal pain, nausea, and constipation may occur due to the disruption of bowel movements. The abdomen may be distended.If acute diarrhea does not improve within 48 hours after taking loperamide, a doctor must be consulted. Prolonged use should only take place after consultation with the doctor. Normally, loperamide cannot cross the blood–brain barrier. However, if the blood-brain barrier is impaired, the drug enters the brain and can cause severe side effects. However, in interaction with other drugs, loperamide can pass the blood-brain barrier more easily. When taken concomitantly with ketoconazole, verapamil, and quinidine, loperamide may cause breathing difficulties. Interactions may also occur with ritonavir, an HIV proteinase inhibitor. It should also be noted that loperamide functionally inhibits acid sphingomyelinase (FIASMA). Any resulting dysregulation can result in serious clinical pathology.
