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Drugs for costipation
These are the drugs that promote evacuationof bowels.
Distinction is made according to theintensity of action.
Laxatives :milder action .used for theelimination 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 byvarious g.i.t.glands and are largely
reabsorbed
Only little is excreted through faeces.
The reabsorption takes place in (a) smallintestine and (b) colon
Laxatives which act mainly in intestine
produce loss of fluid,electrolytes,nutrients.
Those which act on colon produce lessfluid loss
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Excessive use of laxatives should be
avoided except in the following conditions.
Angina, Hemorrhoidbleeding.(straining deteriotes theexisting disease.)
To clear the bowel before surgeryand for x-ray.
Drug-induced constipation.example verapamil.
Expulsion of intestinalparasites,specially with the use ofsome anthelminthics. examplepiperazine preps.
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Abuse of laxatives may lead to
Hypokalemia
Atonic non-functional colon
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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)
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MOA
All purgatives increase the water
content of faeces i) by hydrophilic or osmotic action,
retaining water n electrolytes in thelumen- 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 asprimary action n allowing less time forabsorption of salt n water as secondaryeffect.
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Certain purgatives increase motility viamyenteric plexus.
Laxtives modify the fluid dynamics ofmucosal cell n cause fluid accumulation ingut lumen by one or more of the followingmechanisms.
a) inhibiting sodiumpotasium ATPase ofvillaous cells impairing electrolite n waterabsorption.
b) stimulating adenylcyclase in cryptcells,increasing h2o n electr.secretion.
C ) enhancing PG synthesis in mucosa wchincreases secretion.
d) structural injury to the absorbingintestinal mucosal cells.
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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 of40% 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.MethylcelluloseSemisynthetic,colloidal,hydrophilic
derivative of cellulose.
Generous use of water must be taken with all bulk
forming agents.
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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.
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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 wherestrain has to be avoided.
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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 theintestine.
Magnesium salts also
stimulate intestinal
secretion.
Magnesi
um
sulphat
e
Epsom
salts
Bitter in
taste
5-15g
Magnesi
umhydroxi
de
Milk of
magnesia
Bland in
taste.used as
antacid
also.
15-30ml
Sodium
sulphat
e
Glabers
salts
Bad in
taste
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% inpatients wit Hepatic encephalopathy
it is broken down into acid( e.g. lactic acid) andreduces 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 sodiumbenzote and sodium phenyl acetate.
These combine with ammonia in blood to form
hippuric acid or phenyl acetic glutamine which arerapidly 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 electrolyteimbalance.
Hypokalaemia on regular use.
Long term use must be discourged.It produces colonicatony.
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 bydeacetylation.
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
mucosal damage.
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Anthraquinones Senna and cascara sagrada. Active constituent present as precursor glycoside
On oral administration --->anthraquinone,mainlyOxymethyl anthraquinones are liberated in intestinewhere they are partly absorbed because the release ofactive principle is very slow.
Unabsorbed in sufficient quantity are passed to largeintestine.
In colan the active anthrol form is liberated.
It acts locally or is absorbed into the circulation andgoes for entero-hepatic circulation.
It takes 6-8 hour to produce action. Amount excreted in milk is sufficient to cause
purgation.
Regular use for4-12 months causes colonic atony andrarely mucosal pigmentation.
Pulverised Senna Pod ------->Glaxenna*
Ca salt of sennosida---------->Persennid*
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Choice n use of purgatives
Functional constipation. Ch.bed ridden patients
To avoid straining at stools
(hernia ,cardio vasularafflictions ,piles, fissures n analsurgery)
Food/drug poisoning
After certain antihelmenthics
Preparation of bowel for surgerycolonoscopy 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 or6mg.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.
SPASTICCONSTIPATION
It also named as irritable bowel. stools arehard, round, stone like and difficult topass.
Dietary fibre is the first choice or bulkforming agent may be taken for
wks/months. Stimulants are C/I ted in this ATONICCONSTIPATION ( sluggish bowel )
Commonly seen in advanced age, debilityin laxative abuse.
Plenty of fluids, exercise are measures areto be taken.
In resistant cases bulk forming may betried ( 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 andmorphine etc.)
Correcting the underlying pathology like
vit.B1
defficiency,hypothyroidism,parkinsonsdise
ase DM etc.
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LUBRICANT LAXATIVE
Liquid paraffin is the eg of this type
it acts luminally and pharmacologically it is an inertmineral oil.
It is a foecal lubricant and stool softener as it retardswater 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 surfacetension offluids in the bowel and also act as wettingagent for the bowel,because by emulsifying thecolonic contents facilitate the penetration of water
into faeces.
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