Gauri Gawande(9) Constipation Final.pptx

Pharmacology of Constipation

1. Dr D Y Patil COLLEGE OF PHARMACY, AKURDI constipation Guided by : Prof SHIRODE Sir Created by : Gauri P Gawande Subject : ADVANCED PHARMACOLOGY-ii M pharm 1 st yr

2. contents 1) Introduction 2) Non-therapeutic Measure to treat Constipation 3) Order of Effectiveness 4) Laxatives & Purgatives 5) Purgative abuse 2

3. 5 INTRODUCTION: Constipation is defined as delayed passage of faeces through the intestine with defecation process remaining normal. Evacuation is often associated with straining and is usually incomplete. Constipation refers to bowel movement that are infrequent or hard to pass. The stool is often hard and dry. Dyschezia: Dyschezia means derangement of defecation process which may result due to: Pain arising from haemorrhoids/ fissure Presence of hard dehydrated faecal matter in rectum Sudden cessation of a habitual use of Purgative Normal defecation clear only Descending Colon Purgative entire Colon

4. 6 Non-therapeutic Measure to treat Constipation: Fibrous count in daily diet Daily fluid intake in physical activity Not neglecting nature’s call Selecting alternative drugs which cause lesser constipation as SE Ex: Morphine, anti- cholinergics , Al/Ca gp of Antacids 6) Treating vit B1 deficiency, Hypothyroidism, DM which lead Constipation If all these measures fails then Laxative & Purgatives are used.

5. 7 Order of Effectiveness: Aperient (to get rid of) < Laxative (to loosen) < Emollient (to smooth & soften) < Evaculant (to empty) < Purgative (to clean) < Cathartic ( to utterly clean) Laxative : In higher dose act as Purgative →Result in elimination of soft semi-solid stool Purgative : In smaller dose act as Laxative, In higher Cathartic →Provide mor watery evacuation

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7. 9 LAXATIVES : Mild activity & faecal softens Used : 1) To treat Constipation 2) To avoid undue straining at defaecation in case having hernia, haemorrhoids/ CVD 3) Before/ after any anorectal Surgery 4) In bedridden patients 1) Bulk-forming Laxatives: Wheat bran, Psyllium huck, Ispaghula husk, Semisynthetic cellulose & polycarbophils synthetic fibres Site & MOA: These are luminally active , hydophilic , Indigestible vegetable fibres Stimulate peristalsis & defecation reflexes by ng faecal bulk due to their H₂O absobing & retaining capacity Dosage & latency period: Adequate amt of water must be taken Effect within 1-3 days Bran or husk powder sprinkled over stewed fud SE: -Not absorbed -Bacterial digestion of vegetable fibres within the Colon may lead to bloating & cause abdominal discomfort

8. 10 Dietary fibre is unabsorbable cell wall and other constituents of vegetable food- cellulose, lignins , gums , pectins , glycoproteins and other polysaccharides. Bran is a residual product of flour industry which consist of 40% dietary fibre. Incresaed uptake of dietary fibres causes prevention of functional constipation used for treatment of simple constipation.

9. 11 Psyllium husk derived from the seed of Plantago herb. Psyllium husk contains a hydrophilic mucilloid that undergoes significant fermentation in the COLON shows the Laxative action.

10. 12 2) OSMOTIC LAXATIVES: Lactulose(10g/15ml), Sorbitol “Non-toxic and suitable for long term use” Site & MOA: Luminally active Non-absorbable indigestible disaccharide(sugar) es faecal bulk by Hydrophilic action & due to Osmotic action Dosage & Latency period: 10g BD/TDS with plenty of water to produce 2/3 soft stools /day Latency period: 1-3 days SE: Flatulence(fart ) 3) Some people feel nauseated due to periculiar sweet taste Cramps may occur in few 3) Stool Softener( liquid Paraffin): Site & MOA: Luminally active , pharmacologically inert mineral oil Faecal lubricant, stool softener as it retard water absorption from food Dosage & Latency period: - 15-30ml/day at bed time - 1-3 days Note: Not palatable but can be given in emulsified form/ with juices SE: Frequent use deficiency of fat soluble Vit (A,D,E,K) Forcible administration lead to aspiration lipid pneumonea

11. 13 4) Surfactant Laxatives: Dioctyl Na sulfosuccinate(Docusate Na) Site & MOA: Luminally active agent & anionic surfactant which softens the stool by ing surface tension of fluids in bowel - Act as Wetting agent for bowel by emulsifying Colonic contents & mixing of water into faeces Dosage & Latency period: - 100-400mg orally/ day 1-3 days SE: Nausea as bitter in taste Cramps & abdominal pain Hepatotoxicity if prolonged use Absorption of “Paraffin” hence should not given together

12. 14 PURGATIVES: Used for Complete Colonic Cleansing prior to GI endoscopy Needed for bed ridden patients Needed for neurologically impaired patients Osmotic Purgatives: (lead to watery evacuation) Solutes that are not absorbed in the intestine retain water osmotically and distend the bowel increasing peristalsis indirectly. Mg sulphate, Na sulphate, MgOH (Milk of Magnesia), Na phosphate, PEG Site & MOA: Act on small as well as large intestine Faecal absorption by retaining water by Osmotic effect thus increasing intestinal secretion & peristalsis SE: 1) Vomiting as need to ingested with enough water 2) Mg salts on long term use renal insufficiency

13. 15 2) Irritant/Stimulant Purgatives: They are powerful purgatives: often produce griping. Secretion is enhanced by activation of cAMP in crypt cells as well as by increased PG synthesis. Larger doses of stimulant purgatives can cause excess purgation resulting in fluid and electrolyte imbalance. Hypokalaemia can occur on regular intake. Routine and long-term use must be discouraged, because it can produce colonic atony. Anthraquinones/ Emodins : Senna(most common), Cascara, Aloe Diphenylmethanes/Organic Irritants: Phenolphthalein, Bisacodyl, Sod bicosulphate 5-HT4 agonist: Prucalopride Fixed oil: Castor oil, Croton oil Diphenylmethane Derivatives: It is the only diphenylmethane derivative available in the U.S. It is marketed as entericcoated and regular tablets and as a suppository for rectal administration. Phenolphthalein is a litmus-like indicator which is in use as purgative from the beginning of the 20th century. It turns urine pink if alkaline. Shows protracted action due to its enterohepatic Bisacodyl more popular. They are partly absorbed and re-excreted in bile. Bisacodyl is activated in the intestine by deacetylation. The primary site of action of diphenyl methane is in the colon where they irritate the mucosa, produce mild inflammation and increase secretion

14. 16 Allergic reactions: 1) Skin rashes 2) Fixed drug eruption 3) Stevens-Johnson syndrome have been reported. 4) Morphological alterations in the colonic mucosa have been observed; the mucosa becomes more leaky.

15. 17 ANTHRAQUINILONES(Emodins): Senna obtained from Leaves and pods of certain Cassia sp. Cascara sargada powdered bark of buck-thorn tree which contain Anthraquinolone glycosides SE : Cramps, excessive purging Skin rashes, fixed dose eruption Regular use4 foe 4-12 months cause colonic atony & mucosal pigmentation

16. 18 ii) 5-HT4 agonist: Prucalopride When other laxatives fail to provide adequate relief in chronic constipation in women then Prucalopride is used (marketed in country like Europe, UK and Canada). Prucalopride is shown to have low affinity for 5-HT1B/ID receptor, & cardiac K+ channels. It is therefore, no cardiovascular risk. SE: 1) Headache 2) dizziness 3) fatigue 4) abdominal pain and diarrhea

17. 19 iii) Fixed oil: Castor oil (oldest purgatives) Castor oil is a bland vegetable oil obtained from the seeds of Ricinus communis. It mainlymcontains triglyceride of ricinoleic acid which is a polar long chain fatty acid. Ricinoleic acid, being polar, is poorly absorbed. The primary action is now shown to be decreased intestinal absorption of water and electrolytes, and enhanced secretion by a detergent like action on the mucosa.

18. 20 Purgative abuse: Some individuals are obsessed with using purgatives regularly. This may be the reflection of a psychological problem. Others use a purgative casually, obtain thorough bowel evacuation, and by the time the colon fills up for a proper motion (2-3 days) they get convinced that they are constipated and start taking the drug regularly. Chronic use of purgatives must be discouraged. Once the purgative habit forms, it is difficult to break. Dangers of purgative abuse are: 1. Flairing of intestinal pathology, rupture of inflamed appendix. 2. Fluid and electrolyte imbalance, especially hypokalaemia . 3. Malabsorption syndrome. 4. Protein losing enteropathy. 5. Spastic colitis.

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