Purgatives & Laxatives, by Baqir Naqvi.pptx

Purgatives & Laxatives, by Baqir Naqvi.pptx

1. Purgatives & Laxatives (Pharmacology & Therapeutics-1) Lecture By Dr. Syed Baqir Raza Naqvi (BSc, Pharm-D, M. Phil-Pharmacology) Nazar College of Pharmacy DAKSON Institute of Health Sciences, Islamabad 1

2. Purgatives & Laxatives Drugs used for constipation are called purgatives & laxatives. Constipation It is infrequent or difficult evacuation of hard stool. May also described as “ A sense of incomplete evacuation.” Causes: Irregular bowel habits Spasm of small segments of sigmoid colon. Irritable colon syndrome Mega colon (Abnormally large dilated colon) Hypothyroidism Drugs causing Constipation 1. Opioids analgesics 2. Anti depressants 3 . Ca, Aluminum containing antacids 4. Anti inflammatory agents 2

3. Purgatives These are the drugs which promotes defecation Drugs which are used for evacuation of feces or bowel. Therefore, these are also termed as evacuants. These are also called emollients as they have softening and soothing effects on fecal matter & on GIT. Purgatives may be; Cathartics Laxatives 3

4. Cathartics Laxatives Cathartics are stronger in action. Causes severe purgation. Cause gripping (contraction of colon muscles resulting in spasm & pain) . Cause the passage of watery stool. Cathartics in low doses acts as laxatives. Laxatives are weaker in action. Do not causes gripping Causes the passage of soft formed stool. Laxatives in higher doses act as cathartics 4

5. C haracteristics of Ideal purgatives 5

6. Classification of purgatives & laxatives 6

7. Classification on the basis of mechanism of action 1. Bulk forming purgatives 1 7

8. A). A nthracene Purgatives 1. Natural anthracene purgatives (Senna, Cascara, Rhubarb, Aloe) 2. Synthetic anthracene purgatives (Danthron) B). Others Castor oil, Phenolphthalein, B isacodyl 2. Stimulant purgatives Classification on the basis of mechanism of action 3 . Lubricant purgatives Mineral oil / Liquid paraffin 8

9. Classification on the basis of onset of action 2 9

10. Classification on the basis of Site of action 3 10

11. Summary of commonly used l axatives 11 Book reference: Lippincott's illustrated review of Pharmacology (6 th edition) Page # 410

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13. A. Stimulant Purgatives 1. Senna This agent is a widely used stimulant laxative. Its active ingredient is sennoside (a natural complex of anthraquinone glycosides). Taken orally, senna causes evacuation of the bowels within 8-10 hours. It also causes water and electrolyte secretion into the bowel. In combination products with a docusate containing stool softener, it is useful in treating opioid-induced constipation 13

14. 2. Bisacodyl It is a diphenyl methane derivative. It is stimulant & irritant purgative. Mode of action: It is also called contact purgative because it shows its effect by directly acting on mucosa. It reflexively stimulate the colonic nerve fibers present in the mucosa of large gut & increase peristaltic movements. Dose: Rx’ Dulcolax by Merk 5 mg tablets. 14

15. Clinical Uses It is an orally acting purgative & especially effective in constipation in elderly patients & women after pregnancy. To empty the gut before proctoscopy & radiological examination of gut. Bisacodyl suppositories are used in babies to remove constipation 15 Adverse effects Abdominal pain Because of contraction of colonic muscles. Bisacodyl suppositories can cause rectal irritation. Precautions A Should not be chewed as it leads to emesis because the tablet is enteric coated. Bisacodyl

16. 3. Castor oil It is an irritant/stimulant purgative. It is a fixed oil extracted from castor oil Plant ( Ricinus communis ) . Seeds of castor oil contains two important constituents. Racin (A toxic protein also called as tox -albumin) Ricinolic acid (Important constituent responsible for drastic purgative effects ) Mode of Action In small intestine castor oil undergoes dissolution & is hydrolyzed by pancreatic lipase into triglycerides & ricinolic acid. Castor oil Triglycerides + Ricinolic acid 16 (Pancreatic lipase)

17. Mode of Action (continued) 2. Ricinolic acid then combine with Na & K salts present in small intestine to form stimulant compounds i.e. Na & K ricinolate . These salts then intensify the peristaltic movements in last part of small intestine by stimulating sensory nerve endings . In this way it causes discharge of fecal matter abruptly. 3 . It increases the movement of the muscles that push material through the intestines, helping clear the bowels. Clinical Uses: Limited use now a days. To empty the gut before proctoscopy (Visual examination of rectum or anus), radiation or X-ray examinations 17

18. Adverse effects: Causes gripping May cause severe nausea Its Prolong use may interfere with absorption of nutrients across G.I.T. 18 Precautions Castor oil should not be given at night time but given at day time.

19. B. Bulk forming Purgatives Bulk forming purgatives gives bulk to the feces. They increase the volume of feces by attracting water molecules in GIT, which leads to increase in feces volume that exerts pressure on small and large intestine resulting in easy passage of stool . Characteristics : Cause evacuation of soft form stool Do not cause gripping Have minimum side effects 19

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21. 1. Ispaghula Husk It is a fiber & is a hydrophilic colloid . when taken orally it reaches the gut & swells up by attracting the GIT fluids. So volume of feces increases. This large mass of feces exerts pressure on the intestinal wall, facilitating the evacuation of feces. It should be taken with plenty of water . It shows its effect after 12 hours , or sometimes 2-3 days. 21

22. 2. Mg Sulphate Also called as Epsom salt & is crystalline in nature. Also has cooling effects. Mode of action: When given orally, it reaches the intestine & is not absorbed as it is a heavy ion . It attracts the water from surroundings in the GIT. Thus the bulk of feces increases that exerts pressure that leads to rapid peristaltic movements, results in evacuation of stools. Saline purgatives stimulate the release of Cholecystokinin (A hormone which is secreted from duodenal mucosa. It stimulates the secretions of pancreatic juice & enhances GI motility.) 22

23. 3. Magnesium Hydroxide It is 7.1 - 8.5% aqueous solution of Mg(OH)₂ . In addition to laxative effects it also has antacid properties . Mechanism of Action: All Saline purgatives have same mechanism of action as of Mg sulphate . Brand name: Phillips (Milk of magnesia). 23

24. 4. Lactulose Lactulose is a semisynthetic disaccharide sugar that acts as an osmotic laxative. It cannot be hydrolyzed by GI enzymes. Oral doses reach the colon and are degraded by colonic bacteria into lactic, formic, and acetic acids . This increases osmotic pressure , causing fluid accumulation, soft stools, and defecation. Lactulose is also used for the treatment of hepatic encephalopathy , due to its ability to reduce ammonia levels. 24

25. C. Lubricant Purgatives Mineral oil and glycerin suppositories are lubricants and act by facilitating the passage of hard stools. Precaution: Mineral oil should be taken in an upright position to avoid its aspiration when orally administered. 25

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27. D. Stool softeners ( emollient laxatives or surfactants) Surface-active agents that become emulsified with the stool produce softer feces and ease passage. These include docusate sodium and docusate calcium . They may take days to become effective and are often used for prophylaxis rather than acute treatment. Stool softeners should not be taken with mineral oil because of the potential for absorption of the mineral oil and severe purgation. 27

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29. E. Chloride Channel Activators 29 Lubiprostone , is currently the only agent in this class, works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balance. Lubiprostone is used in the treatment of chronic constipation , because it does not causes tolerance or dependency. Also, it has minimum drug–drug interactions because its metabolism occurs quickly in the stomach and jejunum.

30. Summary of commonly used l axatives 30 Book reference: Lippincott's illustrated review of Pharmacology (6 th edition) Page # 410

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32. Thank you ! 32