Indian Journal of Drugs, 2013, 1(2), 23-37 ISSN: 2348-1684 CHEMICAL AND HERBAL REMEDIES FOR CONSTIPATED PATIENTS: A REVIEW Neeraj Kumar1* and Kamal Kishore2 1Assistant Professor, Shri Ram Murti Smarak College of Engineering and Technology (Pharmacy), Nainital road, Bareilly- 243202, U.P. (India). 2Associate Professor, Department of Pharmacy, M. J. P. Rohilkhand University, Bareilly-243006, U.P. (India). *For Correspondence: Abstract Corresponding author email: Constipation is a condition in which the feces are dry and hard [email protected], Mob: +919897325740 with infrequent difficult evacuation. In 5-25 % children and 2% of Received: 26.08.2013 total population experiences great difficulty with elimination of Accepted: 22.12.2013 food waste, accompanied with pain, fear, and avoidance, treated Access this article online by laxatives, the agents that add bulk to intestinal contents or Website: stimulation of intestinal secretion or motility. The foods like www.drugresearch.in prunes, pears, bran cereals, chemicals like salts of magnesium, Quick Response Code: cellulose, plants like senna, encourage intestinal contractions and easier time moving of bowels. This systematic review contains a huge collection of references for chemicals, natural products, plants having laxative action and also provides the information about medical conditions and diseases responsible for constipation. Keywords: Constipation, laxative, stimulants, transit time, defecation. INTRODUCTION axatives are the agents that increase committee and American college of the ease and frequency of defecation gastroenterology chronic constipation task Lby adding bulk to intestinal contents by force specify that symptoms must have retaining the water in bowel or by occurred for at least 12 weeks in the increasing motility or by stimulating preceding of 12 months (Hsieh, 2005). intestinal secretion (Ashafa, 2011). Several Some conditions of body like metabolic, types of laxative agent are used, including anorectic problems, fiber deficiency in body osmotic agents, bulking agents, stimulants and certain drugs can cause constipation. and lubricating agents. Constipation is a Constipation occurs in diabetic patients condition of bowel idiopathic or originated with unknown pathogenesis or may be due by various identifiable disease processes to autonomic dysfunction with lack of and result into dry and hard feces which synchronicity between gut musculature and making evacuation difficult and result sphincter (Bekele and Kabadi, 1996). In 5- infrequent (Kumar et al., 2007) or defined 25% of children feels pain, fear, avoidance as less than 3 bowel movements per week and great difficulty in elimination of food or according to Rome II functional waste (Alcantaraa and Mayer, 2008) while gastrointestinal disorders coordinating in order adults its prevalence is increased IJOD, 2013, 1(2), 23-37 www.drugresearch.in due to decreased mobility and co-morbid older peoples use laxative more than once medical trauma i.e. spinal card injuries face in a week (Hara et al, 2008). the problem of constipation, distension DISEASES INDUCED CONSTIPATION rectal bleeding, abdominal pain (Ebert, Diabetes mellitus may lower the peristaltic 2012), faecal incontinence (Coggrave et al., movements and secretion of 2006) while some other diseases like gastrointestinal glands (Bekele and Kabadi, Parkinson disease, sialorrhea, dysphagsia 1996) same as in hypothyroidism (Bennett and Dysautonomia, this condition is very and Heuckeroth, 2012). Uremia can common (Evatt et al., 2009). In two third produce mucosal abnormalities which may patients with uremia may face edema to leads to ulceration (Kang, 1993) while ulceration and other gastrointestinal Amyloidosis can decreases the secretion of mucosal abnormalities (Kang, 1993). endocrine cells that secrete hormone like Constipation is more common in women, serotonin and also alters motility of lower socioeconomic populations of rural intestine (Sattianayagam et al., 2009). areas (Hsieh, 2005) due to various risk Neuropathy and spinal cord injury impairs factors like dietary habits, physical the sensory and motor function and slows inactivity, medication age, gender and the transit time. psychological behavior, presently 20-30% of Table-1: Diseases and conditions associated with constipation Category Disorder Probable mechanism of constipation Endocrine and Diabetes mellitus Lowers peristaltic movement and secretion of GI glands metabolic diseases Hypercalcemia Manifests as polyuria, polydipsia, vomiting, dehydration Hyperparathyroidism Causes smooth-muscle atony Hypothyroidism Lowers peristalsis Uremia Gastrointestinal mucosal abnormalities, ulceration Myopathic conditions Amyloidosis Decreased intestinal endocrine cells that secrete hormones like serotonin, altered intestinal motility Myotonic dystrophy Muscular disability Scleroderma Low acid secretion Neurologic diseases Autonomic neuropathy Weakness of nerves Cerebrovascular disease Bowel dysfunction Hirschsprung’s disease Absence of ganglion cells in the distal bowel Multiple sclerosis Abnormalities of colon and slow transit time Parkinson’s disease Dysautonomia-related gastrointestinal symptoms Spinal cord injury Impaired sensory and motor functions. Psychological conditions Anxiety Slow down colonic transit Depression Slow down colonic transit Structural abnormalities Anal fissures, strictures Decreased blood flow in midline portion of anus hemorrhoids Swollen, inflamed veins in the anus or rectum Rectal prolapse or Decrease the intestinal motility and prolonged alimentary rectocele transit time Colonic strictures Structural abnormalities Inflammatory bowel Inflammatory myopathy disease Obstructive colonic mass May be due to colon cancer Other Pregnancy Slower colonic transit may due to progesterone IJOD, 2013, 1(2), 23-37 www.drugresearch.in DRUG INDUCED CONSTIPATION Medications are the important secondary cause of constipation and specially those drugs which affect central nervous system, nerve conduction and smooth muscle function. Such type of constipation can easily measurable by calculating colonic transit time, anorectal manometry, defecography or balloon expulsion test (Hsieh, 2005). The NSAIDs used to relieve pain but also reduces the mucous and bicarbonate secretion while antihistaminic inhibits gastric acid secretion (Souter 2006; McKay, 2012). Anticholinergics drugs like carbamazepine and diuretics may inhibits sodium channels (Ettinger, 1992) while sympathomimitics like ephedrine relaxes the smooth muscles of intestine and muscle relaxant, antimotility drugs like diphenxylate reduce peristalsis and ultimately constipation. Some drugs which may cause constipation during treatment are mentioned in table 2. Table-2: Drugs which causes constipation Class Generic Name Probable mechanism of constipation Analgesic NSAIDs Reduce mucus and bicarbonate secretion Antacids Bismuth Sub silicate Neutralizing the stomach acid and act as buffer Calcium and Aluminum salts Sympathomimitics Ephedrine Smooth muscle relaxation Sympatholytics Clonidine Stimulates absorption and inhibits secretion of fluid and electrolytes and increase intestinal transit time Anticholinergics Benztropine Decreased Ach mediated stimulation of M2 receptors in the GI tract decreasing motility and secretions Anticonvulsant Carbamazepine Stabilizes the inactivated state of sodium channels, potentiate GABA receptors made up of alpha1, beta 2, gamma 2 subunits Antihistaminic Diphenhydramine Inhibition of gastric acid secretion Antimotility Diphenxylate Reduce peristalsis Loperamide Antimuscarinic Oxybutinin CNS adverse events Tolteradine Benzodiazepines Alprazolam CNS adverse events Calcium Channel Verapamil Reduced motility and may promote intestinal electrolyte and Blocker water absorption Diuretics Thiazides Inhibition of sodium-chloride symporter Ganglionic Blocker Trimethaphan CNS adverse events Camsylate Lipid Lowering Cholestramine - Pravastatin Muscle Relaxant Cyclobenzaprine Reduce peristalsis Metaxolone Opiate Codeine Predominately through mu and nu receptors-decreased propulsive peristaltic waves Morphine Psychotherapeutic Phenothiazenes CNS adverse events Sedative-Hypnotic Phenobarbital CNS adverse events Zolpidem Iron Ferrous salts Possibly due to iron induced changes in intestinal bacterial IJOD, 2013, 1(2), 23-37 www.drugresearch.in flora Other Barium Sulfate - Iron Memantine Phenelzine Sucralfate Vinca Alkaloids CHEMICALS WITH LAXATIVE EFFECT The chemicals with natural and synthetic origin play an important role in the development of laxatives. Chemicals from natural origin like Bentonite, cellulose ethulose, lactulose, mannitol while chemicals from semi-synthetic and synthetic origin like carboxymethylcellulose, glycerin, liquid paraffin, sorbitol etc possess very good laxative action. Synthetic drugs like bisacodyl, bisoxatin, dantron, pentaerythritol and salts of magnesium and sodium like magnesium hydroxide, sodium picosulfate are widely used laxatives. Table-3: Chemicals with laxative effect (Bass and Dennis, 1981; Bustos et al., 1991; Sharif et al., 2001; Faruqui and Joshi, 2012) Chemical Name Common Name Type Dose Side Effect (Daily) Bentonite Clay Bulk-Forming 5-10 mg Intestinal Obstruction Bisacodyl Dulcolax Contact 5-15 mg Allergic Reaction Bisoxatin - Contact 60 mg Nausea Carboxy methylcellulose Cellulose Gum Bulk-Forming 2-6 mg Allergy Cellulose Natural Laxative Bulk Laxative 30 g Allergic Dantron Chrysazin Stimulant 5-10 ml Carcinogenic Ethyl hydroxyl ethyl Ethulose Bulk-Forming - Abdominal Pain