drugs for constipation

Drugs for constipation

1. Drugs for constipation Presenter: Ananya Moderator: Dr. Sadhana Holla

2. CONTENTS Definition Causes Symptoms Classification Mechanism of action Choice and use of purgatives Purgative abuse

3. WHAT IS CONSTIPATION? Constipation means delayed passage  of faeces through the intestine with defaecation process remaining normal. Evacuation associated with straining and usually incomplete.

4. If more than three days pass without a bowel movement, the intestinal contents may harden, and a person may have difficulty or even pain during elimination. Straining during bowel movements or the feeling of incomplete evacuation may also be reported as constipation. Normal range: From 3 times daily to 3 times per week.

5. CAUSES:  Ignoring the urge to pass the stools Dehydration Lack of exercise Lack of dietary fiber. Hormonal disturbances. Neurogenic disorders. Systemic illnesses.

6. Symptoms Pain or bloating  headache anorexia lethargy Straining bowel movements Lumpy or hard stools Feeling of blockade in intestine/rectum

7. Laxatives (a perients , p urgatives , c athartics) Drugs that promote evacuation of bowel. Laxative or aperients: milder action, elimination of soft but formed stools. Purgative or cathartic: stronger action, more fluid  and forceful evacuation.

8. Classification:

9. Stimulant purgatives

10. Mechanism of action 

11. Bulk purgatives  DIETARY FIBRE: BRAN Residual product of flour industry  which consist of 40% of dietary fiber. Consist of un- absorbable  cellulose, lignin, pectin, glycoproteins & other polysaccharides.

12. MECHANISM OF ACTION:-  ​ Absorbs water in the intestines, swells, increases water content of feces-softens it and facilitates colonic transit. ​ Dietary fiber supports bacterial growth in colon which contribute to  faecal  mass ​ First line approach  for most patients of simple constipation. ​ Reduces recto sigmoid intraluminal pressure. ​ Relieves symptoms of Irritable bowel syndrome  (IBS)  including pain,  constipation  as well as  diarrhea . ​

13. drawbacks Unpalatable Large quantity (20-40 g/day) needs. Does not soften faeces already present in colon or rectum. Should not be used in patients with gut ulcerations, adhesions.

14. 2.Psyllium & ispaghula Contain natural colloidal mucilage. Forms a bulky gelatinous mass by absorbing by water. Largely fermented in colon increase bacterial mass & softens the faeces.

15. Stool softener 1 .Docusates(dioctyl sodium sulfosuccinate ):   Anionic detergent Softens stools by net water accumulation in the lumen by an action on intestinal mucosa. Emulsifies the colonic content and increases penetration of water into the faeces. 100-400mg/day. Indicated when straining at stools must be avoided.

16. drawbacks Disrupt the mucosal barrier and enhance absorption of many non-absorbable drugs. Eg : Liquid paraffin- should not be combined with DOSS. Cramps and abdominal pain. Liquid preparations cause nausea

17. 2. liquid paraffin

18. Disadvantages Unpleasant to swallow  Small amount passes into intestinal mucosa         produce foreign body granuloma. Swallowing it may trickle in lungs          lipid pneumonia. Carries away fat soluble vitamins with it into the stools; deficiency may occur on chronic use. Interfere with healing in anorectal region, use occasionally.              

19. Stimulant purgatives Powerful purgatives. Produce griping.

20. 1. DIPHENYLMETHANES BISACODYL: Partly absorbed and excreted in bile. Activated in intestine by deacetylation. Irritates  colonic mucosa, produce inflammation & increase secretion. Effects appears within 6-8 hrs.

21. 2.anthraquinones ( emodins ) SENNA & CASCARA SAGRADA: Obtained from leaves and pods of cassia sp., most popularly used as traditional therapy for constipation. After administration, colonic flora converts them to the active form anthrol, acts locally and enterohepatic circulation. Side effects: skin rashes, prolonged use causes mucosal pigmentation, colonic atony.    Lactating mothers.

22. 3. 5-ht 4  agonist PRUCALOPRIDE Facilitates cholinergic neurotransmission. Increases colonic transit without affecting gastric emptying. Improves colonic transit & stool frequency in patients - chronic idiopathic constipation. Marketed in Europe, Canada, and UK for treatment in females.

23. Given in dose of 2-4mg orally OD. Low affinity for cardiac potassium channels &does not prolong Q-T. Side effects: abdominal pain ,headache, dizziness, and fatigue .

24. Lubiprostone     PG analogue (EP 4 receptor agonist).   Stimulating mucosal Cl¯ channels and increasing intestinal secretion.  Used in the treatment of constipation-predominant IBS and chronic constipation.

25. Osmotic purgatives Solutes, not absorbed in the intestine. Increases peristalsis indirectly, retain water osmotically and distend the bowel. Preferred for preparation of bowel before surgery and colonoscopy. Magnesium salt  release cholecystokinin which augments motility and secretion.  All Organic salts used as  osmotic purgatives – similar action but differ in dose.

26. Doses of various osmotic purgatives Mag. Sulfate (Epsom salt): 5-15 g. Sod. Sulfate (Glauber's salt): 10-15 g. Sod.phosphate :6-12 g. Mag. Hydroxide( Milk of magnesia): 8% W/W suspension of 30ml. Sod.pot. Tartrate (Rochelle salt): 8-15 g.

27. lactulose Non absorbable sugar used to prevent or treat acute as well as chronic constipation. Metabolized by colonic bacteria. Used to treat and prevent constipation in pregnant and lactating mothers. In addition to purgative effect, reduces blood ammonia level in patients with hepatic encephalopathy by following mechanism. Reduces luminal pH in the colon (Breakdown product of lactulose is acidic) lactulose Ammonia converted to ammonium ion (not absorbed from gut) Decreases blood ammonia level.

28. Common side effcets – flatus and abdominal cramps. For purgative action, it is given in a dose of 10 gm BD with plenty of water.  In hepatic encephalopathy, 20 gm TDS is given but causes loose motions.

29. lactitol Disaccharide sugar alcohol. Fermented by colonic bacteria into osmotically active and weakly acidic products. Increased water content and lowered  pH. Helpful in hepatic encephalopathy  Side effects – distention ,flatulence, cramps, dyspepsia, nausea and vomiting.

30. Choice and use of purgatives

31. Indication of laxatives is prevention and treatment of acute as well as chronic constipation. Contraindicated in: Undiagnosed abdominal pain, colic or vomiting. Organic constipation: obstruction in bowel, hypothyroidism, hypercalcemia, malignancies, and certain drugs.     Eg : opiates, sedatives, antiparkinsonian, antidepressants etc.

32. Indications of laxatives Functional constipation  Stool frequency: 2days to 2-3 times/day. Constipation may be spastic and atonic. Spastic constipation (irritable bowel):  Stools are hard, rounded, stone like & difficult to pass. First choice laxative: ispaghula or soluble fibres. Stimulant purgatives are contraindicated.

33. ii . Atonic constipation (sluggish bowel) Advanced age , debility or laxatives abuse. Non drug measures: fluids, exercise, regular habits and reassurance. Bulk forming agents or osmotic laxatives like lactulose or mag.hydroxide. Poor compliance: bisacodyl or senna.

34. 2. Bedridden patients Bowel movement may be sluggish, and constipation  anticipated. Prevention:  bulk forming agents; docusates, lactulose, and liquid paraffin. Treatment: enema (soap water/glycerine); bisacodyl or senna orally. Methylnaltrexon:   opioid antagonist acting on opiod receptors in the gut. Counteract opioid analgesic induced constipation  in cancer/palliative care patients without blocking the analgesic action.

35. 3. To avoid straining at stools: To keep the faeces soft. 4. Preparation of bowel for surgery, colonoscopy, abdominal X-ray. Bowel needs to be emptied of the contents including gas. Saline purgative, bisacodyl or senna. 5. After certain anthelmintics Saline purgative or senna- flush out the worm and drug. 6. Food/drug poisoning To drive out the unabsorbed irritant/poisonous material from intestines.

36. Misconception about constipation? That a bowel movements every day is necessary. Wastes stored in the body are absorbed and are dangerous to health or shorten the life span. These misconceptions have led to a marked overuse and abuse of laxatives.

37. Purgative abuse Some individuals are obsessed with using purgatives regularly. This may be the  reflection of psychological problem. Others use a purgative casually, obtain through bowel evacuation, and by the time colon fills up for a proper motion(2-3 days) they get convinced that they are constipated and start taking the drugs regularly.

38. Chronic use of purgatives must be discouraged. Once the purgative habit forms, it is difficult to break. Drawbacks of purgative abuse: Fluid and electrolyte imbalance, hypokalemia. Steatorrhea, malabsorption syndrome. Protein loosing enteropathy. Spastic colitis.

39. reference KD Tripathi, Essentials Of Medical Pharmacology, 8 th edition , Jaypee medical publishers(Ltd) New Delhi 2019, drugs for constipation and diarrhea, Pg. 721-726. HL, KK Sharma, Sharma & Sharma’s principle of pharmacology, 3 rd edition, Paras medical publishers 2017,drugs for constipation, Hyderabad, Pg. 411-414 . Satoskar R.S, Rege N. Nirmal, Bhandarkar S.D, Pharmacology and pharmacotherapeutics, elsevier,24 th edition 2015, pharmacotherapy of constipation, pg.610-620.

40. Thank you