Laxatives

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Laxatives

• Definition
• Laxatives are agents which promote bowel
  evacuation.

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Classification of laxatives

• Laxatives are divided into four groups
• bulk forming agents
• faecal softeners
• osmotic laxatives
• stimulant laxatives

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1- Bulk forming laxatives

• Bulk forming laxatives are indigestible,
  hydrophilic colloids
• They may be natural or synthetic
• Natural e.g. methylcellulose
• Synthetic Polycarbophil
• Mechanism of action
• Act in both the small intestine and colon by
  forming a bulky gel that distends the colon and
  increase peristalsis. They should be taken with
  plenty of water to avoid intestinal obstruction.
  Their action is slow ( onset 12-72 hours) and
  weak (used for maintaining regular bowel
  movements)
• Side effects
• Abdominal distension due to digestion of plant
  fibers by bacteria within the colon
• Contraindications
• fecal impaction or intestinal obstruction

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2- Fecal softeners

• Faecal softeners can be divided into
• Lubricants
• Surfactant agents.
• Lubricants include
• liquid paraffin
• arachis oil
• Site of Action Colon
• Onset of Action 6 - 8 hours
• They make the stool slippery, so that it slides
  through the intestine more easily and at the same
  time decrease absorption of water from stools
  thereby increase stool mass and softness.
• Liquid paraffin is specially used in fecal
  impaction
• Disadvantages
• Not palatable
• Aspiration may occur leading to lipid pneumonia
• Long term administration mal lead to deficiency
  of fat soluble vitamins

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Fecal softeners

• Surfactant agents include
• sodium docusate (oral or rectal)
• Site of Action Small and large intestine
• Onset of Action 12 - 72 hours
• Mechanism of action they soften stools by
  causing water and fats to penetrate the stool,
  making it more bulky and easier to move along the
  GIT.

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3- Osmotic laxatives

• Osmotic laxatives are soluble non-absorbable
  compounds that enter in the substance of stools,
  exert osmotic pressure and increase fluid content
  of stools leading to softening and increased
  bulk.
• Site of Action small intestine and colon
• Onset of Action 0.5 - 3 hours
• 1- Non-absorbable salts magnesium salts
• These result in rapid bowel evacuation. If they
  are given in large doses, defaecation may occur
  in one to two hours.
• Precautions magnesium salts should not be used
  for prolonged periods in patients with renal
  insufficiency for fear of hypermagnesemia
• Side effects may lead to intravascular volume
  depletion and electrolyte disturbances
• Therapeutic uses
• 1- acute constipation
• 2- bowel evacuation prior to surgical procedures
  (oral or enema).

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Osmotic laxatives

• 2- Non-absorbable sugars
• lactulose.
• Glycerine suppository
• Mechanism of action
• They enter in the substance of stools, exert
  osmotic pressure and increase fluid content of
  stools leading to softening and increased bulk.
  In addition to its osmotic effect, lactulose also
  lowers colonic pH thereby stimulating the large
  bowel). Lactulose is slower in action than
  magnesium salts.
• Side effects
• Lactulose is metabolized by colonic bacteria
  producing distension and cramps

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Osmotic laxatives

• C) Balanced polyethylene glycol
• Indications
• A solution of polyethylene glycol, sodium
  sulfate, sodium chloride, sodium bicarbonate and
  potassium chloride (so that no intravascular
  fluid or electrolyte shift occur) is used for
  complete colonic cleansing before
  gastrointestinal endoscopic procedures.
• Smaller doses may be used for treatment of
  chronic constipation. It does not cause abdominal
  distension and cramps like lactulose.

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4-Stimulant laxatives

• Mechanism of action They stimulate intestinal
  motility
• Mechanism of increased intestinal motility
• 1) Direct stimulation of the enteric nervous
  system
• 2) Colonic electrolyte and fluid secretion
• 1- Aloe, senna and cascara
• They are poorly absorbed from the GIT.
  After hydrolysis in the colon, they produce a
  bowel movement in 6-12 hours when given orally
  and within 2 hours when given rectally.
• Side effects
• 1) Chronic use may lead to melanosis coli (brown
  pigmentation of the colon)
• 2) Abdominal cramps
• 2- Castor oil
• It is hydrolysed in the upper part of the
  small intestine into ricinoleic acid which
  stimulate intestinal motility. It acts within 2-6
  hours. It is used to clean the colon before
  surgical and diagnostic procedures

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5- Tegaserod

• Tegaserod is a serotonin 5-HT4 partial agonist.
  Mechanism of the laxative action
• 1- It stimulates 5HT4 receptors on the submucosal
  plexus of nerves stimulate the peristalsis
  reflex. Therefore, tegaserod stimulates motility
  of the stomach, small intestine, large intestine
  but not the esophagus.
• 2- Tegaserod also stimulates chloride secretion
  from the colon leading to increased stool
  liquidity.

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Tegaserod

• Administration orally, before meals because food
  decreases its absorption
• Therapeutic uses
• Chronic constipation (effect on bowel activity
  occurs within 48 hours)
• Irritable bowel syndrome
• Adverse effects
• Diarrhoea
• Headache

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Laxatives suitable for short-term use in acute
constipation

• senna tablets (time to onset of action 6-12h)
• glycerin suppository (time to onset of action
  15-30minutes)
• micro enema 5ml (time to onset of action
  15-30min)
• phosphate enema (time to onset of action
  15-30min)
• For impaction use micro enemas at night to
  soften stool and then phosphate enema or manual
  evacuation next morning

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Treatment of chronic constipation

• Dietary and lifestyle modification
• High fiber diet
• Adequate fluid intake
• Regular exercise
• Heeding of the natures call
• Drug treatment is required if no response occurs

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Treatment of chronic constipation

• Indications for the use of laxatives
• No response to adequate dietary and lifestyle
  advice
• Faecal impaction is present
• Constipation associated with illness, following
  surgery, or during pregnancy
• Elderly patients
• Patients with a pre-existing medical problem in
  which bowel strain is undesirable (e.g. coronary
  heart disease)
• Preparation for an operation/investigation

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Treatment of chronic constipation

• The lowest effective dose of a laxative is used-
  this should be reduced once symptoms resolve
• Laxatives to consider include
• bulk forming laxatives
• of particular value if small hard stools
• these are contraindicated in bowel obstruction or
  faecal impaction
• effect may take several days
• may be appropriate for long-term use when there
  is normal gut motility and otherwise
  uncomplicated constipation
• stimulant laxatives
• effect with 6-12 hours of oral stimulant laxative
  
• osmotic laxatives e.g. lactulose

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Treatment of diarrhea

• 1- Specific treatment
• 2- Nonspecific treatment

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Nonspecific treatment of diarrhea

• 1- Opioid agonists
• 2- Colloidal bismuth compounds
• 3- Kaolin and pectin
• 4- Bile salts binding resins

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1- Opioid agonists

• Mechanism of action
• Increase tone and decrease rhythmic contractions
  through inhibition of pre-synaptic cholinergic
  nerves in the submucosal and myenteric plexuses
  of the colon. This effect leads to increased
  colonic transit and increased fecal water
  absorption and stool hardening
• Opioid agonists used are
• 1- Diphenoxylate no CNS effect in standard
  doses. Higher doses have CNS effects. Prolonged
  use may lead to dependence (atropine is added to
  it to prevent addiction and to help in the
  antidiarrhoeal action)
• 2- Loperamide opioid agonist that does not cross
  the blood-brain barrier and has no potential for
  addiction, no analgesic activity and no potential
  for tolerance.

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2- Colloidal bismuth compounds(bismuth
subsalicylate)

• Mechanism of action
• Releases salicylate in the stomach which is
  absorbed and inhibit PG production leading to
  decreased intestinal motility
• Bismuth is minimally absorbed and passes to the
  intestine where it has an antimicrobial effect

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3- Kaolin and Pectin

• Kaolin is a naturally occurring hydrated
  magnesium aluminiumsilicate and pectin is an
  indigestible carbohydrate derived from apples
• Mechanism of action
• Adsorb bacteria, toxins and fluid in the
  intestine.
• Uses
• Acute diarrhoea
• Adverse effects
• They are not absorbed and has no side effects
  except constipation.

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4- Bile salt binding resin

• Used only in diarrhoea due to diseases or
  surgical resection of the terminal ileum (where
  conjugated bile salts are absorbed). Lack of
  absorption of bile salts leads to diarrhoea
• Drugs
• 1- Cholestyramine
• Mechanism of action
• Bind Conjugated bile salts
• Adverse effects
• 1- Distension
• 2- Constipation
• 3- Fat malabsorption