Drugs for costipation

These are the drugs that promote evacuation of bowels. Distinction is made according to the intensity of action.  Laxatives :milder action .used for the elimination of soft and formed stools  Purgatives or cathartics: strong action. results in more fluid evacuation.  Many drugs in low doses act as laxatives and in large doses as purgatives.
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LAXATIVES

Miscoception about bowel habit leads to excessive use of laxatives Ingested water and fluids are excreted by various g.i.t.glands and are largely reabsorbed Only little is excreted through faeces. The reabsorption takes place in (a) small intestine and (b) colon Laxatives which act mainly in intestine produce loss of fluid,electrolytes,nutrients. Those which act on colon produce less 2 fluid loss

Excessive use of laxatives should be avoided except in the following conditions.

Angina, Hemorrhoid bleeding.(straining deteriotes the existing disease.) To clear the bowel before surgery and for x-ray. Drug-induced constipation. example verapamil. Expulsion of intestinal parasites,specially with the use of some anthelminthics. example piperazine preps.
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Abuse of laxatives may lead to

Hypokalemia Atonic non-functional colon

Classification
1) Bulk forming (eg;dietary
fibre, bran, psyllium, isphagula, methylcellose)

2) Stool softeners (eg; Docusates,liq.paraffin) 3) Stimulant purgatives

(A) Diphenylmethanes (phenophthaleine,Bisacodyl,sodim picosulfate) (B) Anthraquinones(senna,cascara,) (C) 5HT4 agonist (tegaserod) (D) fixed oil (eg; castor oil)

4) Osmotic purgatives (eg; mg.salts. sod.salts and lactulose)

 MOA All purgatives increase the water content of faeces i) by hydrophilic or osmotic action, retaining water n electrolytes in the lumen- increase volume of colonic content n make it propelled easily. ii) by acting on ints. Mucosa, decrease net absorption of water n electrolyte. ints.transit is increased indirectly by the fluid bulk. iii) by increasing propulsive activity as primary action n allowing less time for absorption of salt n water as secondary effect. 6

 Certain purgatives increase motility via myenteric plexus. Laxtives modify the fluid dynamics of mucosal cell n cause fluid accumulation in gut lumen by one or more of the following mechanisms. a) inhibiting sodiumpotasium ATPase of villaous cells impairing electrolite n water absorption. b) stimulating adenylcyclase in crypt cells,increasing h2o n electr.secretion. C ) enhancing PG synthesis in mucosa wch increases secretion. d) structural injury to the absorbing intestinal mucosal cells. 7

Bulk purgatives Dietary fibre (bran)

Most appropriate method and first line approach for prevention and treatment of functional constipation . Consists of unabsorbable cell wall and other constitutes of vegetables food (polysaccharides). Bran consists of 40% dietary fibre Some dietry fibers like gums. lignins. pectins bind with bile acids promotes excretion in faeces.reduces plasma LDL cholestrol. Should not be used in patients with Gastric ulceration,Adhesion,Stenosis. Commonly used are :isphaghula (isogel), husk in granular form.Methylcellulose Semisynthetic,colloidal,hydrophilic derivative of cellulose. Generous use of water must be taken with all bulk forming agents. 8

Stool softener
Docusate Mild laxative Specially indicated when straining at hard stool must be avoided Bitter liquid ,may produce nausea,cramps and abdominal pain. Prolonged use may cause hepototoxicity. It should not be given along with liquid paraffin. because due its detergent action, it can disrupt the mucosal barrier and enhance the absorption of non-absorbable drug like paraffin.

Lubricant laxative
Emollient laxative Example:Liquid Paraffin Mineral oil.Viscous.Mixture of hydrocarbons obtained from petroleum. Pharmacologically inert. Lubricated hard Scybali by coating them Straining avoided due to lubricant action. Disadvantages Bland but unpleasant to swallow(oily). Embracing due to leakage of oil from postanal sphincter. While swallowing it may trickle into lungs and may cause lipid pneumonia(rare). Used mainly in post-operative conditions or where 10 strain has to be avoided.

Osmotic (saline) purgatives

Certain salts, when given orally, are not much absorbed and are retained in g.i.t. They exert osmotic pressure and thus retain considerable amount of water . Thus increases the bulk and distends the intestine. Magnesium salts also stimulate intestinal secretion.
Magnesi um sulphat e Magnesi um hydroxi de Sodium sulphat e Epsom salts Bitter in taste 5-15g

Milk of magnesi a

Bland in taste. used as antacid also. Bad in taste

15-30ml

Glabers salts

10-15g

sodium potassi um tartrate

Rochell e salts

Relative ly pleasan t taste

8-15g

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 These salts have to be dissolved in 150-200ml water and then taken. 1-2 fluid evacuation within 1 hour. Hence they are taken early in the morning before breakfast. In the doses mentioned above causes complete evacuation of bowel. Smaller doses may have a milder laxatives action. They are preferred purgatives for preparation of bowel before surgery and colonoscopy. Food and drug poisoning After purge in the treatment of tapeworm infestation. Mg salts are C/I in renal insufficiency. Sodium salt in C.H.F and other sodium-retaining states.

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lactulose
Neither digested nor absorbed in small intestine. retains water. 4-19g TID, with plenty of water Produces soft formed stool Not a favored purgative because flatulence is common. but lactulose can reduce blood NH3 by 25-40% in patients wit Hepatic encephalopathy  it is broken down into acid( e.g. lactic acid) and reduces the pH of the stool.  NH3 produced by bacteria in colon or due to heptatic dysfunction is  For this purpose ,20g TID or more is needed.  Other drugs used to NH3 in hepatic coma are sodium benzote and sodium phenyl acetate.  These combine with ammonia in blood to form hippuric acid or phenyl acetic glutamine which are rapidly excreted in urine.

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stimulants
Powerful purgatives and often produce griping pain. Large doses of these can cause excess purgation, n produce fluid and electrolyte imbalance. Hypokalaemia on regular use. Long term use must be discourged.It produces colonic atony. C\ I in subacute and chronic intestinal obstruction. Reflexly stimulates gravid uterus.C\I during pregnancy. But often used at the time of labour to help induction of labor. Phenophthalein o Used as indicator and purgative. o It turns urine pink if alkaline.
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 It was added later but is used more popularly. They are partly absorbed and re-excreted in bile. The entero-hepatic circulation is more important for phenophthalein because it produces protracted action.

BISACODYL
Bisacodyl is activated in the intestine by deacetylation. The action of both these are in the colon. Thus action is 6-8 hours. Therefore to be taken at bedtime Bisacodyl is active as suppository also. Suppository acts by irritating the anal and rectal mucosa and reflexy increases Motility. Action with in 20-40 minutes. Regular use by this route may cause inflammation and 15 mucosal damage.

Anthraquinones
Senna and cascara sagrada. Active constituent present as precursor glycoside On oral administration --->anthraquinone,mainly Oxymethyl anthraquinones are liberated in intestine where they are partly absorbed because the release of active principle is very slow. Unabsorbed in sufficient quantity are passed to large intestine. In colan the active anthrol form is liberated. It acts locally or is absorbed into the circulation and goes for entero-hepatic circulation. It takes 6-8 hour to produce action. Amount excreted in milk is sufficient to cause purgation. Regular use for 4-12 months causes colonic atony and rarely mucosal pigmentation. Pulverised Senna Pod ------->Glaxenna* 16 Ca salt of sennosida---------->Persennid* Castor oil--------Absolete.Rarely used now.

Choice n use of purgatives

Functional constipation. Ch.bed ridden patients To avoid straining at stools (hernia ,cardio vasular afflictions ,piles, fissures n anal surgery) Food/drug poisoning After certain antihelmenthics Preparation of bowel for surgery colonoscopy n abd .x-ray.
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 TEGASEROD
New selective 5HT4 partial agonist wch has no action on other receptors It acts n activates prejunctional 5HT4 receptors on intrinsic enteric afferents. It increases CGRP ( calcitonine gene related peptide ) and also increases excitatory transmitter Ach wch inturn helps peristalitic reflex n colonic secretions by increasing cAMPmediated cl- efflux. The propulsive movement is more prominent in colon n less in stomach n ileum. DOSE: 2mg or 6mg.BD before meals. PK: Small fraction is absorbed. unchanged is excreted in faeces.t1/2 is 11 hrs. Indications: 1) IBS; relieves abd pain, bloatinf and increses frequency of stools. 2) ch. Constipation. S/Es: Flautulance, loose motions, headche.
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 Constipation may be spastic or atonic. SPASTIC CONSTIPATION It also named as irritable bowel. stools are hard, round, stone like and difficult to pass. Dietary fibre is the first choice or bulk forming agent may be taken for wks/months. Stimulants are C/I ted in this ATONIC CONSTIPATION ( sluggish bowel ) Commonly seen in advanced age, debility in laxative abuse. Plenty of fluids, exercise are measures are to be taken. In resistant cases bulk forming may be tried ( isphagula, methyl cellulose )
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Functional constipation
It is corrected by Increase in fibre content of regular diet. Increase in daily fluid intake. Increase in physcical activity. Not neglecting the natures call Adjusting the daily routine Selecting alternativr drugs ( wch cause costipation shud be avoided like antihistaminics,anticholinergics and morphine etc.) Correcting the underlying pathology like vit.B1 defficiency,hypothyroidism,parkinsonsdise 20 ase DM etc.

LUBRICANT LAXATIVE
Liquid paraffin is the eg of this type it acts luminally and pharmacologically it is an inert mineral oil. It is a foecal lubricant and stool softener as it retards water absorption from the stools. It is given as 15-30 ml syrup at bed time. Latency period is 1-3 days.

SURFACTANT LAXATIVE
DOCUSATE AND GLYCERINE SUPPOSITORIES ARE EGS OF THIS TYPE. They act luminally. acts by decreasing the surface tension offluids in the bowel and also act as wetting agent for the bowel,because by emulsifying the colonic contents facilitate the penetration of water into faeces.

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