Diarrhea loperamide

Antidiarrheals decrease intestinal peristalsis, which is usually increased when the patient has diarrhea. Examples of these drug s include difenoxin with atropine (Motofen), diphenoxylate witii atropine (Lomotil), and loperamide (Imodium). 

Loperamide stimulates enteric nervous system receptors, inhibiting peristalsis and fluid secretion. It improves stool consistency and reduces the number of stools.21 Consequently, it is most useful in patients who have diarrhea as a prominent symptom. However, it can occasionally aggravate abdominal pain. 

Diarrhea may occur from effects of chemotherapy on the lower portion of the GI tract. Diarrhea can be severe and may need to be treated with intravenous fluids and electrolytes. Infectious causes, such as C. difficile, should be ruled out. Pharmacologic therapy of diarrhea can range from loperamide or cholestyramine to octreotide for severe cases of diarrhea that are refractory to usual treatments. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Loperamide is an opiate that is poorly absorbed from the G1 tract but still retains the ability to inhibit peristalsis It is useful in diarrheas that are just symptomatic and are not due to infection or organic pathology, such as inflammatory bowel disease. 

Loperamide is often recommended for managing acute and chronic diarrhea. Diarrhea lasting 48 hours beyond initiating loperamide warrants medical attention. 

Late-onset diarrhea occurs 1 to 12 days after administration, lasts 3 to 5 days, and can be fatal. Late-onset diarrhea requires aggressive, high-dose loperamide beginning with 4 mg after the first soft or watery stool, followed by 2 mg every 2 hours until symptom free for 12 hours. 

Loperamide is presently used more often as an antidiarrheal drug than as an analgesic, and it is also included in the list of over-the-counter drugs because of its insignificant action on the CNS. It reduces intestinal smooth muscle tone and motility as a result of binding to intestinal opiate receptors. It is used for symptomatic treatment of severe and chronic diarrhea of various origins. The most popular synonym for loperamide is imodium. 

This drug is a structural analog of meperidine and loperamide however, it practically duplicates all of the pharmacological properties of loperamide. Being analogous to loperamide, it is mainly used for treating diarrhea. Synonyms for this drug are fentanest, lep-rofen, and others. 

Diarrhea Do not use loperamide in acute diarrhea associated with organisms that... 

Irinotecan treatment schedules differ from 125 to 150 mg/m2 once a week for 4 wk followed by a 2-wk drug free interval (United States), to 350 mg/m2 once every 3 wk (Europe), or 100 mg/m2/wk or 150 mg/m2 every 2 wk (Japan). Differing intermittent treatment schedules using cytokine support for neutropenia, or intensive loperamide to counteract diarrhea, have also been reported (14). These tolerable CPT-11 regimens have produced median durations of response that range from 5.6 to 10.6 mo in colorectal patients disease stabilization occurs in 30 to 71 % (40). Response rates of 26% and 32% have been reported for previously untreated colorectal cancer patients higher response rates have been reported for non-5-FU-refractory patients (only 7-21%). Symptoms of diarrhea, nausea, and vomiting are common toxicities other side effects are asthenia, abdominal pain, leukopenia, and neutropenia. In the US trials at least one of these adverse... 

Codeine phosphate is still used for diarrhea predominantly based on hypermotility but the longer-acting loperamide is more convenient and has less central nervous system effects. Codeine has an exceptionally low affinity for opioid receptors and its effects are due to the fact that it is converted for approximately 10% to morphine. The active metabolite of morphine, morphine-6-glucuronide, may also accumulate during repeated administration of codeine to patients with impaired renal function. 

The dangers of dependency and addiction clearly preclude the use of such compounds as morphine, meperidine, and methadone as treatment for diarrhea. Antidiarrheal specificity therefore is of paramount importance in choosing among the synthetic opioids and their analogues (e.g., diphenoxylate and loperamide). 

Diarrhea from almost any cause can be controlled with the opioid analgesics, but if diarrhea is associated with infection such use must not substitute for appropriate chemotherapy. Crude opium preparations (eg, paregoric) were used in the past to control diarrhea, but now synthetic surrogates with more selective gastrointestinal effects and few or no CNS effects, eg, diphenoxylate or loperamide, are used. Several preparations are available specifically for this purpose (see Chapter 62). 

Loperamide is a phenylpiperidine derivative used to control diarrhea. However, due to action on peripheral M -opioid receptors and lack of effect on CNS receptors, there is renewed interest in its potential for the treatment of neuropathic pain. Its potential for abuse is considered very low because of its limited access to the brain. It is therefore available without a prescription. 

Opiates produce constipation by affecting receptors in the intestines. Opium extracts were used in this capacity to treat diarrhea. Today there are other related compounds on the market which accomplish the peripheral task without affecting the CNS because of their poor absorption from the Gl tract when taken orally. Imodium A-D , an OTC, contains loperamide. It is also available as a generic OTC. The prescription mixture of diphenoxylate and atropine is called Lomotil . 

The intestinal inhibitory action of opioids can be used for treatment of diarrhea (De Luca and Coupar, 1996). The clinically most important anti-diarrheal opioid is loperamide (Heel et al., 1978). After oral administration, loperamide acts locally within the gastro-intestinal tract. After parenteral administration, the compound is rapidly inactivated and does not reach the CNS. Therefore loperamide does not show the typical central opioid side-effects, has no analgesic action and has no abuse potential. 

Opioid derivatives used to treat diarrhea are listed in Table 27-3. Opium tincture (laudanum) and camphorated opium tincture (paregoric) are naturally occurring opiates that are very potent inhibitors of peristalsis. These natural agents are still available for treating diarrhea, but they have essentially been replaced by newer opioids such as diphenoxylate and loperamide. These newer opioids are somewhat less potent but may produce fewer side effects. 

Loperamide is a phenylpiperidine derivative used to control diarrhea. Its potential for abuse is considered very low because of its limited access to the brain. It is therefore available without a prescription. 

Pharmacological studies with selective agonists have shown that opioid control of intestinal electrolyte transport is predominantly mediated by delta opioid receptors [58], while the gastrointestinal propulsion is under the control of mu receptors [59,60]. The antidiarrheal effects of NEP inhibitors, such as acetorphan, the prodrug of thiorphan, have been compared to those of an opiate agonist, loperamide, in a model of castor oil-induced diarrhea in rats. When administered peripherally, they produced a delayed onset of diarrhea with no reduction in the gastrointestinal transit [61,62], as is commonly observed with loperamide [63],... 

Two drugs widely used to control diarrhea are diphenoxylate [di PHEN ox a late and loperamide [loe PER a mide]. Both are analogues of meperidine (see p. 138) and have opioid-like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis. Side effects include drowsiness, abdominal cramps and dizziness. Since these drugs can cause toxic megacolon, they should not be used in young children or patients with severe colitis. 

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