Constipation and catharsis

W. Grant Thompson,* md

Constipation is endemic in the Western Of the beliefs handed down to us by In the spastic type of irritable colon world. Stool consistence and associated our forefathers, the concept of regu- syndrome the stool is hard, scybalous symptoms are more important than larity is among the most enduring. and often associated with lower abdom¬ stool frequency. The patient's attitude Since antiquity an empty colon has inal pain.4 These symptoms relate to towards his bowel habit is also been equated with purity; and what excessive segmental contraction of the important. Exclusion of "organic" generations of mothers have cherished, lower colon and rectum, and the in¬ disease, reassurance and discussion let no man put asunder. Nevertheless, dividual subsequently has a feeling of of normal variations of bowel habit are there is a logical approach to "con- incomplete evacuation. Constipation necessary first steps in treatment. stipated" patients, and physicians may alternate with periods of diarrhea. Adequate bulk in the stool must be should be firm in their convictions, Hemorrhoids and fissures may com- ensured, either through diet or which, in turn, should be based on plicate the passage of stony stools. Less bulking agents, and bowel retraining science, not fantasy. commonly, obstipation may result from attempted. should be The definition of constipation is elu- an atonic, lax colon, in which pro¬ reserved for episodes of constipation sive. The world's record for rectal con¬ gressive peristaltic activity is decreased, following enforced bedrest, or as a tinence is held by a man who resisted a condition characterized by Sir Arthur preparation for diagnostic procedures. the temptations of the toilet for 368 Hurst as dyschezia.5 This may occur Long-term use should be avoided. days.1 He is said to have become weak spontaneously but is also seen follow¬ after delivering 36 / of feces on June ing chronic abuse of laxatives. La constipation est endemique dans le 21, 1901, but "there was much rejoic- Constipation may result from a wide monde occidental. La consistance des ing in the family". Statistically the variety of local and systemic condi¬ selles et les symptdmes associes "normal population" has from three tions. Perianal disorders such as fis¬ sont plus importants que la frequence bowel movements per week to three a sures or localized proctitis may lead to de la defecation. L'attitude du day.2 The 1% of individuals who fail conscious or subconscious defence of patient a I'egard de ses habitudes outside that range are unusual but not the area by the withholding of stool. de defecation est aussi importante. necessarily abnormal. It is probable that Cancer of the colon, diverticular dis¬ Apres avoir elimine la possibilite the actual frequency of motions is not ease and volvulus are causes of a re¬ d'une cause organique, les relevant, although it may be of great cent change in bowel habit and must premieres etapes necessaires au concern to the patient. More important be rigorously excluded. In hypothyroid- traitement consistent a rassurer le are the consistence of the stool and ism or dehydration, appropriate re¬ patient et a discuter avec lui des associated symptoms. placement therapy may be curative. variations normales des habitudes de Many drugs, including codeine, some defecation. On doit assurer un volume Pathophysiologic considerations antihypertensive agents, iron, aluminum de selles adequat, par le regime and calcium compounds, are constipat- alimentaire ou a I'aide d'agents There are two modes of colonic ing. Inactivity, such as that following mucilagineux, et une reeducation des motor activity.3 The first is propulsive surgery, or travel, especially with habitudes de defecation doit etre contractions or mass movements, long change in time zones, may induce this tentee. Les laxatifs doivent etre recognized by radiologists. These peri¬ distressing nuisance, and it is a frequent reserves aux episodes de constipation staltic rushes are more frequent in diar¬ consequence of pregnancy and of old tels ceux qui suivent les periodes rhea than in constipation. The other age. Endogenous depression often pro¬ d'alitement forcees, ou a la preparation mode is segmental or nonpropulsive ac¬ duces constipation, which may im¬ pour les tests de diagnostic. Leur tivity, which appears to have a mixing prove with antidepressant therapy. utilisation en traitement prolonge and braking function. Such activity Parents reward their children for a doit etre evitee. tends to be decreased in diarrhea and successful bowel action and imbue in increased in some patients with con¬ many the idea that daily movements that succeeds in are essential for cleanliness or ?Associate professor of medicine, University stipation. Segmentation purity. of Ottawa; gastroenterologist, Ottawa Civic isolating part of the colon from the Psychoanalysts have attributed repres- Hospital remainder may generate very high pres¬ sion of defecation to anal eroticism. If Reprint requests to: Dr. W.G. Thompson, sures and result in dilatation the patient is an unmarried it is lst link, Ottawa Civic Hospital, Ottawa, ON proximal girl KIY 4E9 or diverticula formation. said that marriage may effect a cure.® CMA JOURNAL/MAY 22, 1976/VOL. 114 927 I know of no controlled trials to sub- can now be taken between the Weser lulose, hemicellulose and lignin.16 In stantiate this. and the Garonne; that the bustling pestle addition to its hydrophilic bulking prop¬ is still, the canorous mortar mute, and erties fibre may have a cathartic effect Constipation, like the irritable colon, the bowels of men locked for fourteen diverticular disease and is up due to the volatile fatty acids released appendicitis, .... degrees of latitude Without bacterial metabolism. Since there a disease of Western civilization, ap¬ for some to be by is they might months, sure, much evidence that parently attributable to our low-fibre, have carried on a lingering war; but what deficiency of fibre or bulk an refined diet.7 It has been demonstrated can they do without bark [cascara]?14 is important factor in con¬ that the daily stool weight in English stipation, it seems reasonable to in¬ crease the intake of subjects is one third that of Africans Investigation fibre by constipated living under native conditions on an patients.17 As Cleave7 forcefully states, unrefined diet.8 The transit time of the Organic disease must be excluded. this means less refined sugar and flour, bulky African stool is less than half This demands careful history-taking and more natural fruits and whole- that of the British. It would appear that and physical examination and, at least, wheat products. Bran has long been our colons have not had time to adapt sigmoidoscopy.15 Most patients should recognized as an effective to the low-bulk stool that has have a barium examination and and this has had scientific confirma- fibre-free, 9,10,18,19 resulted from the refined diet adopted an estimation of hemoglobin concen¬ tjon MiUer's bran> 6 tQ 1Q tea. over the past century. Thus, partially tration. Recent onset of constipation spoonfuls (12 to 20 g) per day, is a filled colons can generate very high seg¬ demands rigorous exclusion of local cheap and effective laxative.9'10'16,18 mental pressures, accounting for the and systemic disease, particularly car¬ Coarse bran has been shown to have pain and constipation of the spastic cinoma of the colon, hypothyroidism a greater water-holding capacity than colon. Peristaltic activity is disordered and depression. The patient's drug his¬ bran made finer by milling;11 this ac¬ and the patient may have an increased tory should be carefully reviewed to counts for the greater effectiveness of transit time. In individuals who are ensure that there is not a pharmaco¬ the former in improving transit time. given 20 g of unprocessed bran daily, logic cause for his symptoms. The resourceful patient may improve the stool bulk is significantly increased palatability of this material by adding by water entrapped in the interstices of Treatment it to cereals, sauces, meat loaves and the dietary residue.9 Such treatment other foods. Liberal use of whole-wheat speeds up transit in those in whom it General measures bread, breakfast cereals and fresh fruits was slow slows tran¬ and vegetables may assist in and, paradoxically, It is believed that exercise providing sit in those in whom it was rapid. In by many extra bulk. other increased bulk promotes a normal bowel habit. Con- Since bran in words, dietary enforced confinement to therapeutic quantities normalizes colon Coarse versely, bed, is inconvenient, many now motility.9,10 such as after a occlusion or a physicians bran is more effective than fine because coronary prescribe bulking agents. The most sa¬ of the former's greater water-holding fractured hip, is frequently associated tisfactory of these is psyllium hydro¬ capacity.11 with constipation, especially if the pa¬ philic mucilloid (Metamucil, tient must grapple with pulleys and Hydrocil). The individual with constipation may This is useful for preventing constipa¬ bedpans. Adequate fluid must also be tion and other manifestations of the complain of foul breath, furred tongue, ensured. The anorexia, flatulence, headache, irritabil- chronically constipated irritable colon syndrome, as an adjunct colon may be retrained. This is best to the of ity, insomnia, and so on. These were therapy perianal disease, and achieved by using natural reflexes to in the prevention, not the of once considered manifestations of auto- advantage. It is recognized that the treatment, intoxication.12 of this con¬ acute diverticulitis. It is superior to Proponents resting colon may be spurred into ac¬ cept held that were elaborated methylcellulose for this purpose.20 The tion by a meal, particularly breakfast. of use in the gut as a result of constipation. appeal the of bulking agents is Many individuals insist that their their almost lack of side ef¬ In one experiment, however, five bowels function their complete only following fects, is a healthy men were required to eat nor¬ coffee or although impaction potential mally but refrain from defecation for customary morning cigarette, hazard if they are given to patients with although whether this effect is pharma¬ underlying lesions.21 Meta¬ 90 hours.13 Each man complained of or is obstructing cologic, physiologic psychologic mucil contains dextrose as a the above symptoms and experienced uncertain. The re¬ dispersing immediate relief when the situation was regular post-breakfast agent and is best taken in juice, 1 to 3 tirement with a good book to the relax- an enema. Such teaspoonfuls three times a with reversed by prompt solitude of the bathroom may have day seems to ing meals. Some patients have transient relief militate against toxemia, a effect. It is said that a low are now to salutary bloating with the commencement of and the symptoms believed toilet seat results in a squatting posi¬ therapy, but the dose may be be due to distension and mechanical which is more favourable for def¬ adjusted tion, . rectum. masses to achieve a stool that is formed irritation of the In fact, ecation. a outhouse Certainly draughty neither loose and nor and of cotton wool packed into the rectum in is no to commence watery, stony January place the For who are produce identical effects.1213 Many in¬ exercise. To initiate the habit in those fragmented. patients fussy whose colons be there is an expensive flavoured prepa¬ dividuals may empty accustomed to laxatives it may blame such common taking ration. may incorrectly be necessary to use an enema for the symptoms on constipation, and on this first while. A To understand better how psyllium basis in excessive glycerine suppository, exerts its one can the indulge purgation. while inactive pharmacologically, may effect, perform There is no doubt that set in motion the defecation reflex. Pa¬ following simple experiment. In a med¬ constipation icine 5 ml is distressful. Empires have trembled at tient attention to such details, along glass place of the psyllium Add water to make a total the prospect of doing without purga- with the use of as de¬ powder. up bulking agents of 30 ml. Stir and allow to stand for tives. In an exercise of pharmacologic scribed below, may restore even the a few minutes. You will notice that a warfare Britain placed an embargo on most recalcitrant colon to normalcy. the export of purgatives to Napoleon- soft gel forms in the glass. In the colon this action a controlled Europe.14 This strategy was gelling may soften hard, Bulking agents marble-like stool or firm a one. expounded by one Sydney Smith: watery Dietary fibre is described as "unavail- The added bulk promotes normal peri¬ What a sublime thought that no purge able carbohydrate" and includes cel¬ stalsis. 928 CMA JOURNAL/MAY 22, 1976/VOL. 114 A nticholinergics tives and should not be used in drug Abuse of diphenylmethane and an¬ combinations.35 thracene cathartics has been associated Anticholinergic drugs have a greater with a number of serious complications. action on the segmenting or braking Chemical stimulants Long-term use results in dependence of contractions of the colon than on peri¬ the bowel on these for "success¬ Chemical stimulant laxatives can be drugs stalsis.22 Thus, they may be of use in ful" function. In mice and in one wom¬ used in relative are treating colonic spasm when it mani- safety provided they an subjected to long-term administra¬ fests itself as abdominal Anti¬ not abused. The diphenylmethane laxa¬ tion of pain.23 tive intended senna, damaged myenteric cholinergics achieve an effect on the , originally neurons were demonstrated in the as a wine is in colon only in doses that cause side colouring, present many colon.48 Thus, the patient may become effects such as tachycardia and dry patent medicines. Some of the dye is and absorbed and in the urine, physiologically psychologically de¬ mouth. Further, they may aggravate appears pendent on continued purgation. A fre¬ colonic stasis and lead to drying of which, if alkaline, may become pink result is, diar¬ or red.36 It quent paradoxically, the stool.24 Dicyclomine hydrochloride may undergo enterohepatic rhea.49-52 For reasons circulation. The absorbed is be¬ best known to (Bentylol) is said to have a specific drug themselves such patients may conceal effect on smooth muscle with less effect lieved to act directly on the muscle of their laxative habit from the hapless on secretion.25 If this were true it would the distal colon to stimulate peristalsis.37 physician who is dutifully investigating be the best antispasmodic to use. Other¬ It acts within 6 to 8 hours after inges¬ their diarrhea. A of tion and is not inhibited copious radiograph wise, synthetic agents offer no practical by atropine. the colon may show loss of haustrations advantages over are The usual dose is 200 mg. Even in 200 and atropine, expensive times the usual dose it is smooth, tapering contractions and are poorly absorbed from the gut. remarkably known as pseudostrictures.49 In one It is therefore a sad comment that nontoxic, although hypersensitivity re¬ such patient finger clubbing developed, atropine preparations to be taken orally actions have been reported.38 Long-term which delayed recognition of purgative are not available in Canada. Antichol¬ use and abuse, on the other hand, may abuse.53 The have effects clubbing disappeared when inergics have very little applicability in devastating (see below). the senna was to re- a relative of withdrawn, only constipation and should be tried only Oxyphenisatin, phenolph¬ appear when purgative abuse was re- in cases in which abdominal pain pre¬ thalein, has been associated with the de¬ sumed. In these misguided patients the sumably due to colonic velopment of chronic active hepati¬ of laxative abuse segmental tis.35'39"11 The diagnosis may only spasm is not controlled by bulking responsible preparation be confirmed by "locker search" or agents. Patients who have contained DSS, which may have facili- examination of the urine for postprandial tated the of phen¬ pain due to an exaggerated "gastro- absorption oxyphenisatin olphthalein or anthraquinone deriva¬ colic" reflex may occasionally benefit and its transport to the liver.35 Bisa- tives.50'51'53 A further clue to laxative is the most useful of from the administration of an effective codyl (Dulcolax) abuse be an associated this series of and can be may hypokale¬ dose before meals. drugs given mia,51'54'55 which may resemble hyper- either as a suppository or by mouth. aldosteronism.56 and The enteric-coated tablet has no action Malabsorption Stool protein-losing enteropathy have also softeners on the small bowel. If, however, the been described.50-52 tablets are taken with an alkali, Stool softeners are used to lubricate orally the may dissolve, the stool are coating allowing Saline cathartics the and often recommended to act on the small for disease. There drug bowel, causing by surgeons perianal unpleasant gastrointestinal symptoms. The saline cathartics consist of a are many reasons why (li¬ does not work for 6 hours of and sodium salts. should not be used. As¬ variety magnesium quid paraffin) or more following oral administration. Their effect depends in part upon their piration (lipoid) pneumonia has been It is therefore ideally given the night ionization, osmotic effect and low ab- reported in the elderly26'27 and in in¬ before the desired evacuation. sorbability. There is also evidence fants.28 a morning good Mineral oil is solvent for the The will have more that and sulfate ions in the fat-soluble vitamins E and suppository prompt magnesium A, D, K, action, reflexly stimulating the whole gut cause secretion of cholecystokinin.57 and thus may interfere with their ab¬ colon.42 The stimulant effect of the This hormone in turn stimulates intes¬ sorption.29'30 If used in patients with diphenylmethane cathartics is inhibited tinal and colonic motility. Magnesium enteric fistulas it may interfere with local anesthesia.43 sulfate is a if used by (Epsom salt) commonly healing.31 Further, excessively The anthracene glycosides include used saline cathartic. It has a bitter, it cause and may actually incontinence, senna and cascara and are more potent unpleasant taste but causes a semifluid oil leaking through the anal sphincter than The mechanism evacuation in less than 3 hours when cause ani.32 Mineral oil has phenolphthalein.44 may pruritis of the catharsis effected by these orally given in a dose of 5 to 15 g.43 It is even been blamed for gastrointestinal administered is due to direct ac¬ therefore useful to rid the of blood cancer. drugs gut For these reasons mineral oil tion on the submucosal nerve in in with of should be banished from the market plexus patients hepatic coma, drugs the colon; the effect is blocked by prior in poisoning situations and of worms place. application of local anesthetic.45 Senna after administration of a vermifuge. Dioctyl sodium sulfosuccinate (DSS) is the active principle of liquorice pow¬ Milk of magnesia (magnesium hydro¬ is an anionic detergent, which, by low- der. The intact glycoside is ineffective xide), more often used as an antacid, ering surface tension, is thought to fa- in the colon.45'46 When administered is also a saline cathartic but has a cilitate penetration of the fecal mass orally it is apparently hydrolyzed by relatively mild action. Magnesium-con- by water and fat.32 Like mineral oil it colonic bacteria to release aglycones, taining salts should be given with cau¬ produces its laxative effect by softening which cause peristalsis of the trans¬ tion to patients with impaired renal the stool, apparently through inhibition verse and descending colon and de¬ function. Sodium-based compounds of water absorption.34 This substance crease sigmoid segmentation,47 a pro¬ may be taken orally, but the most should be reserved for those situations cess that requires 6 to 8 hours. Agly¬ commonly used sodium-containing sa¬ in which a stool softener is required for cones are ineffective when adminis¬ line cathartic, sodium phosphate-bi- a short period that is, acute perianal tered orally.45 Long-term use leads to a phosphate compound (Fleet), is avail¬ disease. DSS may facilitate the absorp¬ peculiar pigmentation of the rectal mu¬ able as an enema. This hyperosmolar tion of other normally unabsorbed laxa¬ cosa called melanosis coli.48 solution is available in small plastic CMA JOURNAL/MAY 22, 1976/VOL. 114 929 containers. It is sometimes described as lease of gas. It is effective in treating tific convictions and defy this costly a "disposable enema", although one is constipation and changes the nature of and harmful tide. the colon flora.59 The main indication unlikely to encounter an enema that I thank Miss Diane Moore for typing the anyone would wish to keep. This prep- is portal-systemic encephalopathy be- manuscript. aration is most useful in fecal or bari- cause it decreases the availability of um impaction and in preparing the ammonia and other amines from the References rectum for sigmoidoscopy. A hyper- gastrointestinal tract to the brain.00 The 1. GEIB D, JONES JD: Unprecedented case of tonic or any other type of enema may drug is too costly for routine purgation constipation. JAMA 38: 1305, 1902 cause mucosal irritation, which inter- and with long-term use there is risk 2. CONNELL AM, HILTON C, IRVINE G, et al: Variation of bowel habit in two population feres with interpretation of sigmoido- of superinfection.61 samples. Br Med 1 2: 1095, 1965 scopic findings.58 Therefore, it is better There are other traditional laxatives 3. Misntwicz JJ: Colonic motility. Gut 16: 311, to attempt the examination first and that are now considered obsolete. These 1975 4. THOMPSON WG: The irritable colon. Can at least get a look at the mucosa. One include mercury-containing compounds Med Assoc 1 111: 1236, 1974 can administer an enema subsequently such as calomel, and mucosal irritants 5. Hustsr AF: Constipation and Allied Intestinal if necessary. such as croton oil. The latter has been Disorders, London, Oxford U Pr, 1919 6. TRUELOVE SC, REYNELL PC: Diseases of the used to alter the political views of pri- Digestive System, 2nd ed, Oxford, Blackwell, soners and would seem to have limited 1972, p 389 Miscellaneous 7. CLEAVE TL: The Saccharine Disease, Bristol, appeal in a democracy.62 Podophyllum, Wright, 1974 Castor oil, a triglyceride expressed a resin used to remove warts, is no 8. BUluurr DP, WALKER ARP, PAINTER NS: from the seeds of a tropical African Effect of dietary fibre on stools and transit longer considered a practical cathartic. time and its role in the causation of disease. plant, has been used as a cathartic Oral bile salts have a direct stimulating Lancet 2: 1408, 1972 for 3500 years. It is hydrolyzed in the 9. HEATON KW, PAYLER D, POMARE EW, et al: effect on the colon and, in addition, The relationship between intestinal transit small intestine by pancreatic enzymes inhibit the absorption of salt and time and stool weight, and the effects of to release and ricinoleic acid ;43 water.63 The resultant catharsis explains bran (abstr). Gastroenterology 66: 843, 1974 10. LYFORD C, FIsHER J, Buass B, et al: Con- the latter produces hypermotility of the the durability of that ancient prepara- trolled clinical trial of bran in irritable Castor oil pro- bowel syndrome (abstr). Gun Res 23: 247, small and large bowel. tion still on druggists' shelves, Caroid 1975 duces abdominal cramping and loose and Bile Salts. Because of the adverse 11. KIRWAN WO, SMITH AN, MCCONNELL AA, bowel motions within 2 hours and if effects of bile salts in the stomach and et al: Action of different bran preparations used in excess may induce electrolyte on colonic function. Br Med 1 4: 187, 1975 the existence of many other effective 12. ALVAREZ WC: Intestinal autointoxication. Phy- imbalance. Because of this violent ac- agents, this preparation can no longer stol Rev 4: 352, 1924 tion it is unsuitable for routine use and be considered useful.64 13. DONALDSON AN: Relation of constipation to should be reserved for situations in intestinal intoxication. JAMA 78: 884, 1922 14. SMITH 5: cited in In England Now. Lancet 2: which total colonic cleanout is neces- 1079, 1973 sary, such as for a barium enema or Conclusion 15. THOMPSON WG: Sigmoidoscopy. Can Med Assoc / 110: 683, 1974 colonoscopy. Constipation, like beauty, "often lies 16. CUMMINGS JH: Progress report: dietary fibre. is a synthetic disaccharide in the eyes of the beholder". It is a Gut 14: 69, 1973 not digested by small intestinal or pan- sobering thought that many patients 17. Laxatives and . Med Lett Drugs creatic enzymes. In the colon it is meta- Ther 15: 98, 1973 purge themselves because they think 18. PAINTER NS: Aetiology of diverticular disease. bolized by the microflora, with resul- they are constipated.TM In one study, 14 Br Med 1 2: 156, 1971 tant acidification of the stool and re- 19. COWGILL OR, ANDERSON WE: Laxative ef- of 20 patients using laxatives habitually fects of wheat bran and "washed bran lfl for constipation were able to maintain healthy men. JAMA 98: 1866, 1932 20. CAss U, WOLF LP: A clinical evaluation of Table I-Types of laxatives available and a satisfactory bowel habit during a certain bulk and irritant laxatives. Gastro- time lags in their action 2-week period on a placebo.65 Thus, enterology 20: 149, 1952 21. SOUTER WA: Bolus obstruction of gut after the physician must first determine that use of hydrophilic colloid laxatives. Br Med I Type Time lag the patient is indeed constipated. Laxa- 1:166, 1965 tives should be reserved for episodes of 22. PAINTER NS, TRuU.OvE SC, ANDRAN GM, et Bulking agents Bran al: Effect of morphine, prostigmine, pethidine constipation such as may occur after and Pro-Banthine on the human colon in Psyllium Days diverticulosis studied by intra-luminal pressure Methylcellulose J barium radiography or enforced bed- recorders and cineradiology. Gut 6: 57, 1965 rest. The types of laxatives available 23. Ivav KJ: Are anticholinergics of use in the Stool softeners Mineral oil* irritable colon syndrome? Gastroenterology Dioctyl sodium D and the time lags in their action are 68: 1300, 1975 summarized in Table I. 24. INGELFINOER FJ: The treatment of chronic sulfosuccinate ays constipation. Ann NY Acad Sci 58: 503, 1954 In a lecture delivered nearly 40 years 25. GOODMAN LS, OILMAN A: The Pharmaco- Chemical Diphenylmethane ago Witts66 urged his colleagues to re- logical Basis of Therapeutics, 4th ed, New stimulants Phenolphthalein .6 hours York, Macmillan, 1970, p 540 Oxyphenisatin* r frain from ritual purgation of their pa- 26. ZURROW HB, SERGAY H: Lipoid pneumonia Bisacodyl J tients. He pointed out that purging "any in a geriatric patient. I Am Geriatr Assoc unfortunate patient who is robust 14: 240, 1966 Anthracene gly- 27. FREIMAN DO, ENGELBERO H, MEJUtIT WH: enough to stand the strain" pre- and Oil aspiration (lipoid) pneumonia in adults: a cosides 6 hours study of 47 patients. Arch Intern Med 66: Senna postoperatively is a practice "rooted in 11, 1940 Cascara archaic and primitive beliefs, rather 28. EL5TON CW: Pneumonia due to liquid paraf- than physiology and pathology." Seri- fin: a chemical analysis. Arch Dis Child 41: Saline cathartics 428, 1966 Magnesium 3 hours ously ill patients in a state of precarious 29. Effect of mineral oil on the absorption of hydroxide hydration can ill afford further gastro- carotine and vitamin A in man (E). Nutr Sodium sulfate Rev 6: 170, 1948 intestinal loss of fluid. In spite of in- 30. JAVERT CT, MACRI C: Prothrombin concentra- junctions by clinical pharmacologists tion and mineral oil. Am J Obstet Gynecol Miscellaneous Castor oil - 2 hours 42: 409, 1941 Lactulose against their long-term use, over 700 31. DONALD I: Practical Obstetrical Problems, 3rd Calomel * laxative preparations are available over ed, London, Lloyd Lake, 1964, p 743 Croton oil* the counter in the United States,17 and 32. JoNas A, GODDING EW: Management of Podophyllum* Constipation, Oxford, Blackwell, 1972, chap Caroid and Bile Salts* these are dispensed literally by the 2, part 2, p 38 ton.67 Like King Lear in the storm, the 33. Bovo JT, DOLL R: Gastro-intestinal cancer and the use of . Br I Cancer *Obsolete physician must stand firm on his scien- 8: 231, 1954 930 CMA JOURNAL/MAY 22, 1976/VOL. 114 34. SAUNDERS DR. SILLERY I, RACHMILEWFVL D: Effect of dioctyl sodium sulfosuccinate (DSS) on structure and function of human and rat Bactriin intestine (abstr). Gastroenterology 68: 979, DaImane. 1975 35. NA.ss K: Oxyphenisatin and jaundice. JAMA 212: 1961, 1970 36. FANTus B, DYNIEwIcz JM: Phenolphthalein Roche studies. Elimination of phenolphthalein. Roche JAMA 110: 1656, 1938 37. BLIcK P, BERARDI JB, WOZASEK 0: The mode of the laxative action of phenolphthalein. Am J Dig Dis 9: 292, 1942 (fiurazepam) 38. AsItAMOwITz EW: Phenolphthalein today: a critical review. Am J Dig Dis 17: 79, 1950 39. REYNOLDs TD, LAPIN AC, PamIts RL, et al: Puzzling jaundice: probable relationship to laxative ingestion. JAMA 211: 86, 1970 40. MAcHARDY G, BALART LA: Jaundice and oxyphenisatin. Ibid, p 83 Rx summary Rx summary: 41. PEARsON AJG, GRAINGER JM, SCHAUER DJ, Indications Useful in all types of insomnia et al: Jaundice due to oxyphenisatin. Lancet IndicatIons characterized by difficulty in falling asleep, 1: 994, 1971 frequent nocturnal awakenings and/or early The following types of infections when caused by morning awakening. Dalmane' can be admin- 42. KocK NG, KEWENTER J, SUNDIN T: Studies susceptible pathogens: istered effectively for short-term and intermittent on the defecation reflex in man. Scand I * Genitourinary tract infections: acute, recurrent, use in patients with recurring insomnia and Gastroenterol 7: 689, 1972 and chronic cystitis, pyelonephritis, urethritis poor sleeping habits; however, the safety and 43. GOoDMAN LS, GILMAN A: Pharmacological (including uncomplicated gonococcal urethritis), efficacy of long-term use has not been 1020 prostatis, vaginitis, cervicitis, salpingitis established. Basis of Therapeutics, op cit, p * Upper and lower respiratory tract infections Contraindications Known hypersensitivity to the 44. HusAcHER MH, DOERNBERO S: Laxatives. (particularly chronic bronchitis and including drug and, because of lack of sufficient clinical II. Relationship between structure and po- acute and chronic otitis media) experience, in children under fifteen years of age. tency. J Pharm Sci 53: 1067, 1964 * Gastrointestinal tract infections Warnings Safety in women who are or may 45. HARDCASTLE JD, WILKINS JL: The action of It is not indicated in infections due to Pseudomonas, become pregnant has not been established sennosides and related compounds on human Mycoplasma, or viruses. hence as with all medication, Dalmane should colon and rectum. Gut 11: 1038, 1970 Contraindications be given only when the potential benefits have on the Evidence of marked liver damage; blood dyscrasias; been weighed against possible hazard to mother 46. SMITH B: Effect of irritant purgatives known hypersensitivity to trimethoprim or sulfona- and child. myenteric plexus in man and the mouse. Gut Precautions Use in fhe Elderly: In elderly and 1968 mides; or marked renal impairment where repeated 9: 139, serum assays cannot be carried out. debilitated patients, it is recommended that the 47. WALLER 5: Comparative effects of codeine Infants during the first few weeks of life (especially dosage initially be limited to 15 mg to preclude and senna on the motor activity of the left the development of oversedation, dizziness colon (abstr). Gut 16: 407, 1975 premature infants). and/or ataxia reported in some patients. For the time being, during pregnancy. Use in Emotional Disorders: The usual precau- 48. BocKus HL, WILLARD JH, BANK J: Melanosis Adverse reactions tions are indicated for severely depressed coli: the etiological significance of the an- Most frequent: nausea; vomiting; gastric intolerance; patients or those in whom there is any evidence thracine laxatives. A report of 41 cases. and rash. of latent depression, particularly the recognition JAMA 111: 1, 1933 Less frequent: diarrhea; constipation; flatulence; that suicidal tendencies may be present and 49. RAWSON MD: Cathartic colon. Lancet 1: anorexia; pyrosis; gastritis; gastroenteritis; urticaria; protective measures may be necessary. 1121, 1966 headache; and liver changes (abnormal elevations Potenfiafion of Drug Effects: Since Dalmane has a central nervous system depressant effect, 50. FRENCH JM, GADDIE R, SMITH N: Diarrhoea in alkaline phosphatase and serum transaminase). 1956 Occasionally reported: glossitis; oliguria; hema- patients should be advised against the simul- due to phenolphthalein. Lancet 1: 551, tuna; tremor; vertigo; alopecia; and elevated BUN, taneous ingestion of alcohol and other central 51. CUMMINO5 JH, SLADEN GE, JAMES OFW, NPN, and serum creatinine. nervous system depressant drugs during et al: Laxative-induced diarrhoea: a continu- Hematological changes, occurring particularly in Dalmane' therapy. ing clinical problem. Br Med 1 1: 537, 1974 Physical and Psychological Dependence: As the elderly, are mostly transient and reversible with any hypnotic, caution must be exercised in 52. HEIZER WD, WARSHAW AL, WALDMANN TA, (primarily, neutropenia and thrombocytopenia; less administering to individuals known to be et al: Protein-losing gastroenteropathy and frequently, leukopenia, aplastic or hemolytic anemia, addiction-prone or those whose history suggests malabsorption associated with factitious diar- agranulocytosis, and bone marrow depression). they may increase the dosage on their own rhea. Ann Intern Med 68: 839, 1968 Precautions initiative. 53. SILK DDA, Glasovi JA, MURRAY CRH: Re- As with other sulfonamide preparations, benefit General: All patients should be cautioned versible finger clubbing in a case of purgative should be critically appraised against risk in against engaging in activities requiring precision abuse. Gastroenterology 68: 790, 1975 patients with liver damage, renal damage, urinary and complete mental alertness such as in obstruction, blood dyscrasias, allergies, operating machinery or driving a motor vehicle 54. SCHWARTZ WB, RELMAN AS: Metabolic and or bronchial asthma. shortly after ingesting the drug. Should renal studies in chronic potassium depletion Dalmane' be used repeatedly, periodic blood resulting from overuse of laxatives. J Clin The possibility of superinfection with a non-sensitive 1953 organism should be borne in mind. counts and liver and kidney function tests Invest 32: 258, Dosage and administration should be performed. The usual precautions 55. HOUGHTON BJ, Pa.tRS MA: Chronic potassium Children under 12 years of age: should be observed in patients with impaired depletion due to purgation with cascara. Br Young children - according to weight renal or hepatic function. Patients' reactions will / 1: 1328, 1958 be modified to a varying extent depending on Med Under 2 years - 2.5 ml suspension, twice daily dosage and individual susceptibility. 56. FLEISCHER N, BROWN H, GRAHAM DY, et al: 2 to 5 years -2.5 to 5 ml suspension or ito 2 Adverse Effects Dizziness, drowsiness, Chronic laxative induced hyperaldosteronism pediatric tablets, twice daily lightheadedness and ataxia may occur. These and hypokalemia simulating Bartter's syn- 6 to 12 years -5 to 10 ml suspension or 2 to 4 adverse effects are particularly common in elderly drome. Ann Intern Med 70: 791, 1969 pediatric tablets or 1 adult tablet, twice daily and debilitated patients. (See Precautions). 57. HARVEY RF, READ AE: Saline purgatives act Adults and children over 12 years of age: Severe sedation, lethargy, disorientation, prob- by releasing cholecystokinin. Lancet 2: 185, Standard dosage -2 adult tablets, twice daily ably indicative of drug intolerance or overdose, 1973 Minimum dosage and long-term treatment - have been reported. 1 adult tablet, twice daily Dosage Dosage should be individualized for 58. DEVROEDE G, LaitIcHa M, SANcHEZ G, et al: Maximum dosage (overwhelming infections)- maximal beneficial effects. The usual adult Effects of hypertonic on the rectal 3 adult tablets, twice daily dosage is 3D mg before retiring. In elderly and/or mucosa (abstr). Ann R Coil Phys Surg Can Uncomplicated gonorrhea -2 adult tablets, 4 times debilitated patients, it is recommended that 8: 27, 1975 daily for 2 days therapy be initiated with 15 mg until individual 59. WESSELIUS-DE CASPARIS A, BRAADBAART 5, For acute urinary tract infections, 2 tablets twice responses are determined. Moderate to severe BERGH-BOHLKEN GE, et al: Treatment of daily should be given until the urine becomes insomnia may require 15 or 30 mg. chronic constipation with lactulose syrup: sterile. Supply Dalmane' 15, capsules (orange and results of a double blind study. Gut 9: 87, When the patient has a history of chronic reinfection, ivory) 15 mg, 100 and 500. 1968 Dalmane 3D, capsules (red and ivory) 30 mg, 1 tablet twice daily can be given as prophylaxis. 100 and 500. 60. ELKINOTON SG: Lactulose. Gut 11: 1043, Suppiy 1970 Suspension (aniseed-flavoured), each teaspoonful Complete prescribing information available mg on request. 61. Dusos RJ, SAVAGE DC, SCHAEDLER RW: The (5 ml) containing 40 mg trimethoprim plus 200 @Reg. Trade Mark indigenous flora of the gastrointestinal tract. sulfamethoxazole. Bottles of 100 and 400 ml. 10: 23, 1967 Pediatric tablets, containing 20 mg trimetho- Dis Colon Rectum prim plus 100 mg sulfamethoxazole. Bottles of 100 62. GADDUM JH: Pharmacology, 4th ed, London, and 500. Oxford U Pr, 1953, p 251 Adult tablets, containing 80 mg trimethoprim 63. MEKJIAN HS, PHILLIPS SF, HOFFMAN AF: plus 400 mg sulfamethoxazole. Bottles of 100 and Colonic secretion of water and electrolytes 500. induced by bile acids: perfusion studies in man. J Clin Invest 50: 1569, 1971 Product monograph available on request. 64. HEATON KW: The importance of keeping bile salts in their place. Gut 10: 857, 1969 *Trade Mark of Hoffmann-La Roche Limited 65. GREINER T, BROSS I, GOLD H: A method for @Reg. Trade Mark evaluation of laxative habits in human sub- jects. I Chronic Dis 6: 244, 1957 66. Wsrrs U: Ritual purgation in modern medi- cine. Lancet 1: 427, 1937 Hoffmann-La Roche Limited 67. TRAvELL I: Pharmacology of stimulant laxa- Q Hoffmann-La Roche Limited \E1III.E1I.,f Vaudreull, Quebec tives. Ann NY Acad Sd 58: 416, 1954 Vaudreull, Quebec CMA JOURNAL/MAY 22, 1976/VOL. 114 931