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Adverse effects of laxatives: fact and fiction.

Laxatives are generally well tolerated and may be considered safe drugs. When taken at much higher than the recommended doses (laxative abuse) some side effects may occur (e.g. hypokalemia, metabolic alkalosis, renal tubular damage). It is controversial whether the laxatives currently used may lead to morphologic changes of the autonomous nervous system of the colon. Melanosis coli is due to pigment-laden macrophages within the submucosa. It occurs after long-term intake of anthraquinones and has no functional consequences. No case of 'cathartic colon' has been observed during the last few decades, and we can assume that it was probably caused by laxatives which are no longer in use.

Alkalosis↗

Laxative abuse.

Two types of laxative abuse are described, namely habitual abuse and surreptitious abuse. Phenolphthalein and the anthraquinone derivatives have been most abused in this respect. Long-term anthraquinone use may lead to melanosis coli and cathartic colon, with typical histological and radiological features. Surreptitious abuse presents as a factitious illness with diarrhoea, hypokalaemia, abdominal pain and thirst, as well as melanosis coli. Over 90% of cases occur in women, many of whom work in a paramedical situation. Wider recognition of the range of normal bowel habit and a cultural change with rejection of Victorian mores and concepts of 'intestinal auto-intoxication' have led to a decrease in inappropriate laxative consumption. However, they are still widely prescribed and bought. Although it was as long ago as 1937 that Witts [108] drew attention to the dangers associated with the use of laxatives, his lesion still needs to be preached today.

Cathartics↗

[Effects of lactulose on intestinal functions in mice and rats].

Effects of lactulose on transit of charcoal meals and the luminal water and insoluble contents in the intestinal tract of rats and mice were investigated. The ED50 value for lactulose to induce diarrhea was 3.8 g/kg (p.o.). The sufficient dose (5.4 and 8.6 g/kg, p.o.) needed to produce diarrhea increased the luminal water content of the small intestine and the caecum in rats and mice and sped transit of the intestinal charcoal in mice. In addition, the administration of lactulose at 5.4 g/kg significantly decreased the luminal insoluble contents of the rat small intestine. These results indicate the cathartic effect of lactulose in smaller animals such as rats as well as humans and suggest the possible application of full doses of lactulose to flush the luminal contents from the small intestine.

Animals↗

Pharmacological studies on root bark of mulberry tree (Morus alba L.)

Pharmacological studies were done on the root bark of mulberry tree and pharmacological effects were compared with the clinical effects of "Sohakuhi" in Chinese medicine. n-Butanol- and water-soluble fractions of mulberry root had similar effects except for those on the cadiovascular system. Both fractions showed cathartic, analgesic, diuretic, antitussive, antiedema, sedative, anticonvulsant, and hypotensive actions in mice, rats, guinea pigs and dogs. There appears to be a correlation between the experimental pharmacological results and the clinical applications of mulberry root found in the literature on Chinese medicine.

Analgesics↗

Treatment of childhood constipation by primary care physicians: efficacy and predictors of outcome.

OBJECTIVE: Childhood constipation accounts for 3% of visits to general pediatric clinics and as many as 30% of visits to pediatric gastroenterologists. The majority of children who experience constipation and whose caregivers seek medical care are seen by primary care physicians such as pediatricians or family physicians. Little is known about how primary care physicians treat childhood constipation or the success of their treatments. With this study, we prospectively examined which treatments primary care physicians prescribe to children who present for the first time with constipation and how effective those treatments are. METHODS: A total of 119 children who were between 2 and 7 years of age (mean: 44.1 +/- 13.6 months) and presented to 26 different primary care physicians (15 pediatricians and 11 family physicians) for the treatment of constipation for the first time participated in this study. Parents completed daily diaries of their child's bowel habits for 2 weeks before starting treatment recommended by their primary care physician and again 2 months after treatment. The prescribed treatment was identified by reviewing office records of the treating physicians. RESULTS: After 2 months of treatment, 44 (37%) of 119 children remained constipated. In the majority (87%) of cases, physicians prescribed some form of laxative or stool softener. The most commonly prescribed laxatives were magnesium hydroxide (77%), senna syrup (23%), mineral oil (8%), and lactulose (8%). In nearly all cases, a specific fixed dose of laxative was recommended; in only 5% of cases were parents instructed clearly to adjust the dose of laxative up or down to get the desired effect. In approximately half of the cases, physicians recommended some sort of dietary intervention. Some form of behavioral intervention was mentioned in the office records of approximately one third of cases; however, in most cases, little detail was provided. In 45% of cases, physicians prescribed disimpaction using oral cathartics, enemas, or suppositories followed by daily laxatives. In 35% of cases, physicians prescribed daily laxatives without any disimpaction procedure. In the remainder, physicians prescribed only dietary changes (5%), the use of intermittent laxatives (9%), or no therapy (7%). Treatment success corresponded to how aggressively the child was treated. Specifically, children who underwent some form of colonic evacuation followed by daily laxative therapy were more likely to have responded to treatment than were those who were treated less aggressively. CONCLUSION: Primary care physicians tend to undertreat childhood constipation. After 2 months of treatment, nearly 40% of constipated children remain symptomatic.

Cathartics↗

Adverse effects of drugs used in the management of constipation and diarrhoea.

Most laxatives, if used intermittently in the absence of contraindications, are relatively safe. Bulking agents may diminish absorption of some minerals and drugs, but this is not usually clinically significant. Ispaghula can cause serious allergic reactions. The chronic ingestion of stimulant laxatives has been blamed for the development of the 'cathartic colon', but there are no definitive studies which have demonstrated this. Dantron (danthron) preparations should only be used in older patients and the terminally ill because of the risk of hepatotoxicity with this drug. Oral oxyphenisatine should no longer be used. Senna would appear to be the stimulant laxative of choice during pregnancy and lactation. Bisacodyl is the polyphenolic derivative of choice. Lactulose, sorbitol and lactilol rarely cause significant adverse effects. Magnesium salt laxatives and phosphate enemas can cause serious metabolic disturbances in babies and young children. Liquid paraffin is contraindicated if there is any risk of aspiration. Interference with the absorption of fat soluble vitamins would not appear to be clinically significant. Docusate sodium may potentiate the hepatotoxicity of other drugs, but reports of this are rare. The role of cisapride in constipation has not been established. Antidiarrhoeal drugs are second line drugs whose use is aimed at minimising inconvenience and discomfort. No antidiarrhoeals can be recommended for children under 4 years of age. Loperamide is the drug of choice in older children and adults. The atropine component of diphenoxylate/atropine combinations can cause significant adverse effects. Bismuth salicylate is an inconvenient treatment for travellers' diarrhoea as large frequent doses of the liquid formulation are needed. Some bismuth can be absorbed and there is the potential to cause encephalopathy. Octreotide, methysergide and cholestyramine have a role for specific causes of diarrhoea only. Octreotide is effective in high output states from the small or large bowel, with few adverse effects. Clonidine and lidamidine may have a role in the treatment of chronic diabetic diarrhoea. The role of lidamidine in nondiabetic chronic diarrhoea has not been established.

Antidiarrheals↗

Which drugs affect potassium?

A number of drugs can affect potassium levels by a variety of different mechanisms. Diuretics remain the most important cause of drug-induced alterations. ACE inhibitors may produce hyperkalaemia, particularly in patients with autonomic neuropathy, adrenal insufficiency, renal impairment and when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). Cathartic and/or diuretic abuse should be suspected when hypokalaemia occurs in young patients suspected of having an eating disorder. NSAIDs may occasionally produce hyperkalaemia, particularly in patients with renal impairment or when used with ACE inhibitors. Sympathomimetics and theophylline derivatives may lower serum potassium levels, but this is usually only of clinical significance when overdosage occurs.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II).

Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth subcitrate, sucralfate); antacids and prostaglandin analogues; antiemetics and prokinetics (metoclopramide, domperidone, cisapride); and antispasmodics. In Part II, we consider the anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics.

Anti-Inflammatory Agents, Non-Steroidal↗

Economic aspects of pharmacotherapy for chronic constipation.

Constipation is one of the most common digestive complaints. It is a symptom, not a disease. The subjectivity that this involves means that assessments of clinical epidemiology, socioeconomic costs and pharmacotherapy are difficult, since there is no definition of 'normal' bowel habit. Although constipation can affect all ages, the problem increases with age, and is of particular concern for those who are frail and in long term care. Cultural influences may affect the prevalence in older people. Drug therapy of constipation cannot be considered in isolation, since there are issues in the prevention of constipation and the principles of good management that also apply. Furthermore, some consideration of the pathophysiology and diagnosis is important. This is because a number of remediable causes can be identified, and the diagnostic process involves patient education, which in turn may be effective in reducing costs. It is the complaint of constipation which leads either to self-medication or to consultation with the medical profession. Both of these courses of action have a significant influence on utilisation of laxatives (cathartics), obtained both over-the-counter and by prescription. Although there are a large number of laxative preparations available, therapy has changed little in half a century. Costs may vary considerably, and with such a significant problem there is a need for comparative studies. However, study methodologies are difficult, and a significant placebo response may be found. Education and preventive measures have been shown to reduce laxative use and costs in institutions. Unfortunately, there are few comparative studies of individual laxatives and even fewer cost-effectiveness studies. Those that there are have been based in institutions, and so extrapolation to other situations may be difficult. In general, little attention is given to constipation. It is, however, an area with significant resource implications in which education and preventive measures have been shown to be beneficial. Even so, there is still a need for good comparative studies, particularly where cost effectiveness is concerned.

Aged↗

An analysis of hypermagnesemia and hypomagnesemia.

Serum magnesium (Mg) was measured in 6,252 patients; in 1,246 (19.9%) the value was abnormal. Hypermagnesemia (serum Mg greater than or equal to 3.9 mg/dl) was observed in 51 patients (0.8%) and hypomagnesemia (Mg less than or equal to 1.5 mg/dl) in 165 (2.6%). Hypermagnesemia was found in patients with renal failure treated with Mg-containing antacids or cathartics, or with eclamptic convulsions treated with Mg sulfate. The most frequent clinical finding of hypermagnesemia was urinary disturbance, although various other neurological signs and symptoms were observed. Hypomagnesemia was seen in patients with various diseases such as cancer, hepatic cirrhosis, cerebrovascular disease, and generally poor condition. Abnormalities of electrolytes other than Mg were also frequently observed. The most common clinical findings of hypomagnesemia were personality changes and depression. The differentiation from psychiatric disease is important.

Antacids↗

The fine structure of colonic submucosal nerves in patients with chronic laxative abuse.

Ultrastructural studies of colonic biopsies from patients with a history of long-term laxative abuse, predominantly with stimulant cathartics such as anthraquinone derivatives or bisacodyl, indicated that submucosal nerve fibres may be severely damaged in relation to dosage and time of addiction. The main pathological features found were ballooning of axons, reduction of nerve-specific cell organelles, lysosomal activity, and increase of melanin-loaded macrophages. Morphometric analysis revealed a significant increase (P less than 0.01) in axonal area, with simultaneous reduction of neurotubules. Nerve endings showed a significant decrease of neurosecretory granules when compared with those of normals. It is concluded that these alterations might be a morphological correlation to the clinically evident disturbance of gut motility in patients with chronic laxative abuse, because the intact enteric plexus system is a prerequisite for coordination of normal gut peristalsis.

Cathartics↗

Drug overdose--reducing the load.

OBJECTIVE: To review available information about various methods for reducing gastrointestinal absorption of a poison or drug. DATA SOURCES: Articles on overdose and accidental poisoning generated by the Australian Medlars Service and concentrating on the period between 1985 and 1990 were surveyed. Earlier studies were included if relevant. STUDY SELECTION AND DATA EXTRACTION: English language articles with an emphasis on studies using objective methods to measure individual and comparative efficacy of gastrointestinal decontamination techniques were selected. A total of 65 articles were reviewed. DATA SYNTHESIS: Gastric emptying procedures (gastric lavage or emesis caused by syrup of ipecac) are only effective if performed within one hour of drug ingestion. Gastric lavage is superior to syrup of ipecac. Oral administration of activated charcoal is more effective than either gastric emptying procedure, and is recommended for most cases of poisoning. Cathartics (sorbitol) can be used with activated charcoal. Whole bowel lavage with polyethylene glycol is indicated in selected cases of potentially lethal overdose where the toxic substance cannot be absorbed by charcoal and has passed the pylorus. CONCLUSIONS: Children--syrup of ipecac can be given at home to children older than 12 months. Most children who reach hospital can be treated by charcoal alone. ADULTS--Most patients are managed with supportive care and, in the absence of contraindications, a single dose of activated charcoal if seen within four hours of ingestion of the poison or drug. Gastric lavage is used if the patient presents within one hour of ingestion and has clinical features of toxicity.

Adult↗

Bulimarexia and related serious eating disorders with medical complications.

Bulimarexia, an eating disorder that is characterized by binge eating followed by self-induced vomiting or abuse of cathartic or diuretic drugs, has been defined as both a sequela of anorexia nervosa and a distinct eating disorder. In this review the presentation, prevalence, and complications of the various eating disorders--anorexia nervosa, pica, rumination disorder of infancy, and bulimia/bulimarexia--are discussed. Detailed attention is given to the potential medical hazards of bulimarexia. These hazards may be categorized according to the organ system affected or the individual behavioral components of bulimarexia. Because bulimarexia is commonly practiced in secrecy, its presentation may be in the form of one of its medical complications. Therefore, physicians must know the behavioral components of bulimarexia and its potential medical hazards. Optimal care of these patients requires collaborative efforts from a physician and behavioral therapist.

Adolescent↗

Fatal hypermagnesemia.

Severe symptomatic hypermagnesemia is a rare clinical problem that predominantly results from excess exogenous magnesium intake in patients with renal failure. This report describes an elderly woman who was given a magnesium-containing cathartic for pre-operative bowel preparation in the context of unrecognized acute renal failure. She subsequently developed one of the highest serum magnesium concentrations ever reported. The hypermagnesemia was successfully treated with continuous arteriovenous hemodialysis, but she ultimately died from complications of hypermagnesemia, that included junctional bradycardia, myocardial infarction and respiratory failure. This case illustrates the importance of ensuring intact renal function prior to administering large quantities of oral magnesium. More specifically, large doses of magnesium salts should be avoided in patients with acute renal failure.

Acute Kidney Injury↗

Inhibitory actions of laxatives on motility and water and electrolyte transport in the gastrointestinal tract.

Castor oil and magnesium sulfate were studied for their effects on gastrointestinal contractile activity in vivo. Ricinoleic acid, the active ingredient in castor oil, magnesium sulfate and mannitol were studied and compared for their effects on net water and electrolyte absorption in vitro. Extraluminal strain gauge transducers were implanted in dogs and used to monitor the circular smooth muscle activity of the antrum, duodenum, ileum and colon after water, castor oil or a 30 percent solution of magnesium sulfate. Substances were tested during the interdigestive (fasted) and digestive (fed) states. Decreases in total activity were found for both cathartics in the antrum and ileum. Further analysis revealed that decreases in the ileum occurred primarily by a decrease in contractile rate, whereas antral decreases could be attributed primarily to a decrease in force per contraction. Proximal colonic activity tended to decrease after laxatives and feeding. The effects of ricinoleic acid, isotonic and hypertonic solutions of magnesium sulfate and mannitol on net water and electrolyte absorption were tested on everted segments of hamster jejunum. Sodium ricinoleate (2.0 mM) reduced net water transport by 48 percent (P smaller than .01). Magnesium sulfate, like mannitol, only reduced net water absorption when present as a component of a hypertonic mucosal solution. The results suggest that both inhibition of water absorption and reduced circular smooth muscle activity may be important factors in castor oil- and magnesium sulfate-induced catharsis.

Animals↗

[Paraquat poisoning and hemoperfusion with activated charcoal].

Paraquat is a common herbicide in Spain. In our country there are a few cases of this intoxication and it presents a high mortality even if the patients ingest a minimal amount. We present two cases of accidental poisoning with paraquat. These patients were admitted three hours after ingestion of toxin. They were treated with with orogastric lavage, activated charcoal, N-acetylcysteine, Fuller's earth, cathartics, support measures and hemoperfusion with activated charcoal. With these treatments both patients had a undetectable levels of paraquat 48 hours after and improvement of their symptoms, gastric and intestinal predominantly . We present the graphics of evolution of the plasma and urine levels of paraquat in both patients. We review the different aspects of treatment and update of this poisoning.

Accidents↗

Lethal iatrogenic hypermagnesemia.

The administration of magnesium is an effective therapeutic option in such conditions as preeclampsia, ischemic heart disease, cardiac arrhythmia, and asthma. It has also been used as a cathartic in the treatment of constipation. As a medical therapy, magnesium enjoys an acceptable safety record. Because magnesium is almost exclusively excreted in the urine, significantly elevated levels of magnesium are typically anticipated only in patients with renal dysfunction. With wider application, emerging reports suggest that additional factors such as intestinal hypomotility and chronic constipation should be considered before using magnesium to avoid toxicity.

Aged↗

[A case of successfully treated nifedipine-poisoning].

Calcium antagonists have been prescribed for treatment of hypertension and several other diseases, and the incidence of poisoning involving these agents is increasing. We encountered and successfully treated a case of nifedipine poisoning. The patient was a 52-year-old man who ingested 76 tablets of nifedipine 20 mg while drinking alcohol. He was brought to a clinic and transferred to our emergency department. Since systolic blood pressure on arrival was 110 mmHg, primary care involved gastric lavage, infusion of lactated Ringer solution, and administration of activated charcoal and cathartics. Hypotension subsequently developed and continuous infusion of dobutamine was initiated. Arrhythmia did not appear during the course of treatment, and the patient was discharged after four days.

Calcium Channel Blockers↗