CONSTIPATION

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www.pharmacology4students.com

• A ppt on
• DRUGS FOR CONSTIPATION
• AND DIARRHOEA
• by
• Dr DEEPIKIA SONI ,Dr. PRASHANT,MD.
• Dr Swati Prashant,MD.
  
• 
  
  
  
• 
  
  

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CONSTIPATION

• DRUGS FOR CONSTIPATION
• LAXATIVE - milder in action ,elimination of soft
  but formed stools.
• PURGATIVE - stronger in action, more fluid
  evacuation.

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CLASSIFICATION

• BULK FORMING-
• Dietary fiber
• Bran ,psyllium ,ispaghula ,methylcellulose
• STOOL SOFTENER-
• Docusates(DOSS), Liquid paraffin
• STIMULANT PURGATIVES-
• Diphenylmethane
• Phenolphthalein,Bisacodyl,sodium picosulfate

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• STIMULANT PURGATIVES-
• 1 Diphenylmethane-Phenolphthalein,Bisacodyl,sodi
  um picosulfate

2 Anthraquinones(emodins)-senna ,cascara
sagrada 3 Fixed oil-castor oil
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OSMOTIC PURGATIVESMagnesium salts
suflate,hydroxidesodium salts sulfate
,phosphatesod.pot.tartratelactuloseC/I Renal
insuffTEGASEROD-5-HT-4 AGONIST-releases
ACH,Calcitonin,CGRP,-IBS
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BULK PURGATIVE-

• DIETARY FIBRE- BRAN
• Consist of unabsorbable cellulose
  ,pectins,glycoprotiens other polysacchrides.

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MECHANISM OF ACTION-

• Absorbs water in the intestines,swells,increases
  water content of faeces-softens it and
  facilitates colonic transit
• binds bile acid promote their excretion in
  faeces degradation of cholestrol in liver is
  enhanced plasma LDL-cholestrol is lowered

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USES-

• Reduces Recto sigmoid intraluminal pressure
• Relieves symptoms of irritable bowel syndrome
  (IBS) including pain ,constipation as well as
  diarrhoea ,and colonic diverticulosis.

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DRAWBACKS

• Unpalatable
• does not soften faeces already present in colon
  or rectum
• It should not be used in patients with gut
  ulcerations, adhesions stenosis when feacal
  impaction possibility

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PSYIIIUM ISPAGHULA

• They contain natural colloidal mucilage
• MECHANISM OF ACTION
• Forms a gelatinous mass by absorbing by water
• USES
• Useful in both constipation diarrhoea
• DRAWBACKS
• If taken dry ,can cause esophageal impaction
• DOSE
• 3-12 gm refined husk freshly mixed with water or
  milk and taken daily acts in 1-3 days.

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STOOL SOFTNER

• DOCUSATES(DIOCETYL SODIUM SULFOSUCCINATEDOSS
• MECHANISM OF ACTION
• By a detergent action, it emulsifies the colonic
  content
• USES
• Indicated the when straining at stools must be
  avoided

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• DRAWBACK
• can disrupt the mucosal barrier and enhance
  absorption of many non-absorbable drugs, eg
  liquid- paraffin should not be combined with it
• Cramps and abdominal pain can occur.
• It is bitter liquid preparation may cause
  nausea.
• Hepatotoxicity is feared on prolonged use.

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LIQUID PARAFFIN

• It is a viscous liquid a mixture of petroleum
  hydrocarbon
• DRAWBACK
• -Unpleasant to swallow
• -Carries away fat soluble vitamins with it into
  the stools deficiency may occur on chronic use
• USES
• -Soften stools and is said to lubricate hard
  scybali by coating them
• DOSE
• 15-30ml/day-oil as such or in emulsified form

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STIMULANT PURGATIVES

• DIPHENYLMETHANES
• Phenolphthalein
• Bisacodyl
• Activated in intestine by deactylation
• Both this ,in colon irritate the mucosa,
  semiformed motions occur after 6-8 hours
• DOSE
• -Phenolphthalein-60-130 mg (not to be chewed)
• -Bisacodyl 5-15 mg DULCOLAX 5 mg tab

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DRAWBACK

• Mucosa becomes more leaky
• Allergic reaction-
• skin rashes, fixed drug
  eruption
• Stevens-Johnson syndrome have been reported

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Sodium Picosulfate

• MACHANISUM OF ACTION-
• It is hydrolyzed by colonic bacteria to the
  active form ,which then acts locally to irritate
  the mucosa and activate myenteric neurons
• USES
• Used to evacuate the colon for colonoscopy or
  surgery.
• DOSE
• 5-10 mg at bed time

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ANTHRAQUINONES

• Senna is obtained from leaves and pod of certain
  Cassia sp., while Cascara sagrada is the powdered
  bark of the buck-thorn tree.
• These contain anthraquinone-glycosides ,also
  called Emodins.

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DOSE PURSENNID 18 mg

• MACHANISM OF ACTION-
• In the colon bacteria liberate the active
  anthrol form, which either acts locally or is
  absorbed into circulation- excreted in bile to
  act on small intestine
• The active principle acts on the myenteric plexus
  to increase peristalsis and decrease segmentation

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DRAWBACK

• SKIN RASHES,FIXED DRUG ERUPTION ARE SEEN
  OCCASIONALY
• REGULAR USE FOR 4-12 MONTHS CAUSES COLONIC ATONY
  AND MUMUSOSAL PIGMENTATION (MELONOSIS)

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CASTOR OIL

• Castor oil is a bland vegetable oil obtained from
  the seeds of ricinus communis
• MECHANISM OF ACTION
• It mainly contain triglyceride of ricinoleic
  acid which is a polar long chain fatty acid
• Decreased intestinal absorption of water and
  electrolytes

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DRAWBACKS

• Due to its unpalatably,
• Frequent cramping, rather violent action,
  possibility of dehydration and after constipation
  (due to complete evacuation of colon ),it is no
  longer a favored purgative

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OSMOTIC PERGATIVE

• Solute that are not absorbed in the intestine
  retain water osmotic ally and distend the bowel
  increasing peristalsis indirectly
• DOSE
• Mag.hydroxide (as 8 w/w suspension-milk of
  magnesia)30mlbland in taste also used an
  antacid.
• Mag.sulfate(epsom salt)515gbitter in taste
• Sod.sulfate (glaubers salts) 10-15g bad in
  taste

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Sod.phosphate6-12,taste not unpleasant
Sod.pot.tartrate (Rochelle salt )8-15
mg,relatively pleasant tasting

• LACTULOSE
• It is a semi synthetic disaccharide of fructose
  and lactose which is neither digested nor
  absorbed in the small intestine-retains water.

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DIARRHOEA

• For the treatment of diarrhoea therapeutic
  measures may be grouped into
• A) Treatment of fluid depletion, shock and
  acidosis.
• B) Maintenance of nutrition.
• C) Drug therapy.

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Treatment of fluid depletion, shock acidosis.

• REHYDRATION

INTRAVENOUS ORAL
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NEW FORMULA WHO-ORS

• CONTENT
• NaCl 2.6g
• KCl 1.5g
• Trisod.citrate 2.9g
• Glucose 13.5g
• Water 1 L

• CONCENTRATION
• Na (ion) 75ml
• K (ion) 20ml
• Cl (ion) 65ml
• Citrate 10ml
• Glucose 75ml

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MAINTENANCE OF NUTRITION

• Boiled potato, buffalo milk ,rice ,chicken soup,
  banana, sago etc
• DRUG THERAPY
• Specific antimicrobial drugs
• Nonspecific antidiarrhoel drugs

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A . Antimicrobials are of no value In diarrhoea
due to noninfective causes, such as

• Irritable bowel syndrome (IBS)
• Coelic disease
• Pancreatic enzyme deficiency
• Tropical sprue (except when there is secondary
  infection)
• thyrotoxicosis

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B. ANTIMICROBIAL ARE USEFUL ONLY IN SEVERE
DISEASE

• Travelers diarrhoea mostly due to ETEC ,
  campylobacter or virus cotrimoxazole,
  norfloxacin , doxycycline and erythomycin reduces
  the duration and total fluid needed only in
  severe cases.
• EPECis less common ,but causes shigella like
  invasive illness. Cotrimoxazole,colistin,nalidixic
  acid or norfloxacin may be used in acute cases
  and in infants

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• Shigella enteritisonly when associated with
  blood and mucus in stools may be treated with
  ciprofloxacin ,norfloxin or nalidixic acid
  cotrimoxazole and ampicillin are alternatives
• Salmonella typhimurium enteritis is often
  invasive severe cases may be treated with a
  fluroquinolone , cotrimoxazole or ampicillin
• Yersinia enterocolitica common in colder places
  , not in tropics. cotrimoxazole is the most
  suitable drug in severe cases ciprofloxacin is
  an alternative

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ANTIMICROBIALS ARE REGULARLY USEFUL in

• Cholera though not life saving ,tetracyclines
  reduce stool volume to nearly 0.5 . Cotrimoxazole
  is an alternative ,especially in children .
  Lately,multidrug resistant cholera strains have
  arisencan be treated with norfloxacin/ciprofloxin
  ampicillin and erythromycin are also effective

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• CAMPYLOBACTER JEJUNINORFLOXIN AND OTHER
  FLUOROQUINOLONES ERADICATE THE ORGSNISM FROM THE
  STOOLS AND CONTROL DIARRHOEA.ERYTHOMYCIN IS
  FAIRLY EFFECTIVE IN CHIDREN.
• CLOSTRIDIUM DIFFICILE PRODUCE ANTIBIOTIC
  ASSOCIATED PSEUDOMEMBRANOUS ENTEROCOLITIS .THE
  DRUG OF CHOICE FOR IT METRONIDAZOLE ,WHILE
  VANCOMYCIN GIVEN ORALLY IS AN ALTERNATIVE
  .OFFENDING ANTIBIOTIC MUST BE STOPPED .

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• Diarrhoea associated with bacterial growth in
  blind loops/diverticulitis may be treated with
  tetracycline or metronidazole
• Amoebiasis metronidazole , diloxanide furoate
• Giardiasis are effective drugs

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NONSPECIFIC ANTIDIARRHOEAL AGENTS AND THEIR
INDICATION
ABSORBANTS ISPAGHULA PSYLLIUM METHYLCELLULOSE (IBS) ILEOSTOMY/COLOSTOMY DIARRHOEA
ANTISECERTORY SULFASALAZINE MESALALAZINE RECECADOTRIL ULCERATIVE COLITIS, (IBD) TRAVELLERS DIARRHOEA ,CARCINOID,
ANTIMOTILITY CODEINE DIPHENOXYLATE-ATROPINE LOPERAMIDE NONINFECTIVE OR MILD TRAVELLERS DIARRHOEA ,IDIOPATHIC DIARRHOEA IN AIDS
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ABSORBANTS

• These are colloidal bulk forming substance which
  absorb water swell. ispaghula and other bulk
  forming colloids are useful in both constipation
  and diarrhoea

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ANTISECRETORY DRUGS

• SULFASALAZINE (SALICYLAZOSULFAPYRIDINE) it is a
  compound of 5- amino salicylic acid (5-ASA) with
  sulfa pyridine linked through an azo bond that
  has a specific therapeutic effect in inflammatory
  bowel diseases like ulcerative colitis and
  crohns disease

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MECHANISM OF ACTION

• The azo bond is split by colonic bacteria to
  release 5-ASAsulfapyridine
• It inhibits both COXLOX ,decrease PG and LT
  production.
• Inhibition of cytokine ,PAF,TNF ALPHA NUCLEAR
  TRANSCRIPTION FACTOR GENERATION
• THUS MIGRATION OF inflammatory cells into bowel
  wall is interfered and mucosal secretion is
  reduced

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DOSE

• A dose of 3- 4 gm /day induces remission over a
  few weeks
• Maintenance therapy with 1.5 -2 gm/day has been
  found to postpone relapse as long as taken

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DRAWBACKS

• Rashes ,fever joint pain , haemolysis and blood
  dyscrasias
• Nausea ,vomiting , headache, malaise and anaemia
  are other frequent side effect
• Oligozoospermia and male infertility is reported.
• sulfasalazine interferes with folate absorption

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MESALAZINE

• These are 5-ASA is the active moiety in
  ulcerative colitis, formulated as delayed
  release preparation by coating with acrylic
  polymer .
• MECHANISM OF ACTION-
• (same as
  sulfasalazine)
• Less than half of the 5-ASA released from these
  preparation is absorbed , acetylated in the liver
  and excreted in urine

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DRAWBACK

• Nausea ,diarrhoea, abdominal pain and headache
  but are mild and less frequent.
• Rashes and hypersensitivity reaction are rare
• Has nephrotoxic potential
• Contraindicated in renal and hepatic impairment.
• DOSE
• A DAILY DOSE OF 2.4 g

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RACECADOTRIL

• This is a prodrug is rapidly converted to
  thiorphane ,an enkephalinase inhibitor
• MACHANISM OF ACTION
• Decreases intestinal hypersecrition ,without
  affecting motility by lowering mucosal Camp due
  to enhanced ENK action.

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DRAWBACK

• Nausea, vomiting, drowsiness flatulence
• DOSE
• 100mg (children 1.5 mg/kg) TDS for not more than
  7 days

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ANTIMOTILITY DRUG

• These are OPIODS drugs which increase small bowel
  tone and segmenting activity, reduce propulsive
  movement and diminish intestinal secretion while
  enhancing absorption

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CODIENE

• This opium alkaloid has prominent constipating
  action at a dose of 60 mg TDS.
• SIDE EFFECTS ARE Nausea, vomiting and dizziness.

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DIPHENOXYCOLATE

• Synthetic opioids, chemically related to
  pethidine used exclusively as constipating agent
  action is similar to codeine

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LOPRAMIDE

• It is an opiate analogue with major peripheral
  opioids and additional weak anticholinergic
  property
• DOSE
• 4mg followed by 2mg after each motion (max in a
  day)2mg BD for chronic diarrhoea

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BIBLIOGRAPHY

• K.D TRIPATHY

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