LAXATIVES

Anjan Nepali
Grisha Gurung
Pratibha Mahato
Constipation

Constipation usually refers to disorder of bowel function

associated with infrequent bowel movements, staining, or hard
stools.

• Symptoms: Nausea +/- vomiting , Abdominal distension, Abdominal

and Rectal pain, Flatulence, Loss of appetite, Lethargy, Depression
 Constipation
Criteria for functional constipation:
Based on the presence of 2 of the following for at least 3 months with symptoms
onset at least 6 months prior to diagnosis:
• Straining during at least 25% of defecations
• Lumpy or hard stools in at least 25% of defecations
• Sensation of incomplete evacuation for at least 25% of defecations
• Sensation of anorectal obstruction/blockage for at least 25% of defecations
• Manual maneuvers to facilitate at least 25% of defecations (e.g. digital evacuation,
support of the pelvic floor)
• Fewer than 3 defecations per week
• Loose stools are rarely present without the use of laxatives.
MANAGEMENT
Non Pharmacological Management
For most people, intermittent constipation is best prevented:
• high-fiber diet,
• adequate fluid intake,
• regular exercise, and
• the heeding of nature’s call.
Patients not responding to dietary changes or fiber supplements should
undergo medical evaluation before initiating long-term laxative
treatment.
PHARMACOLOGICAL MANAGEMENT:
LAXATIVES
• BULK FORMING LAXATIVES
• STOOL SURFACTANT AGENTS(SOFTNERS)
• OSMOTIC LAXATIVES
• STIMULANT LAXATIVES
• CHLORIDE SECRETION ACTIVATORS
• OPOID RECEPTOR ANTAGONIST
• SEROTONIN 5-HT RECEPTOR AGONISTS
1. Bulk forming laxatives
• Bulk-forming laxatives are indigestible, hydrophilic colloids that
absorb water, forming a bulky, emollient gel that distends the colon
and promotes peristalsis.
• This is accomplished by increasing the bacterial content of stool by
fermentation of fiber (fermentable fiber) or simply by drawing water
into the stool (nonfermentable fiber).
• Bacterial digestion of plant fibers within the colon may lead to
increased bloating and flatus.
• Psyllium, methylcellulose, polycarbophil
• Effect in 10-12 hrs
• Swallowed with water/milk

• CI: Patients with obstructive symptoms, megacolon, adhesions,

stenosis.
• ADR: Abdominal distension: The fermentation process by bacteria
contributes to the production of gas, which leads to bloating. This side
effect usually improves with time.
Preparations:
• Bran: 20-40g/day
• Psyllium hydrophilic mucilloid: ISOVAC (65g/100g)
• Ispaghula: ISOGEL (27g/30g), NATURECURE (49g/100g)
• Methylcellulose: 4-6g/day
2. SOFTNERS
• These agents soften stool material, permitting water and lipids to
penetrate.
• They may be administered orally or rectally.
• Mild laxative, used when straining at stools must be avoided.

• Common: Docusate (oral or enema) and glycerin suppository.

Mineral oil (liquid paraffin)
• clear, viscous oil that lubricates fecal material, retarding water
absorption from the stool.
• used to prevent and treat fecal impaction in young children and
debilitated adults.
• It is not palatable but may be mixed with juices
• Can cause fat soluble vitamin deficiency, aspiration pneumonia.

• Dose: 15-30ml/day
Docusate
• surfactants that allow mixing of aqueous and fatty substances in the
stool.
• The docusate salts also increase intestinal fluid secretion
• Acts in 1-3 days
• Dose: 100-400mg/day

• Cramps & abdominal pain. Bitter taste & may cause nausea
• Hepatotoxicity in prolonged use
3. OSMOTIC LAXATIVES
A. Non-absorbable sugar or salts
• used for the treatment of acute constipation or the prevention of
chronic constipation

• Magnesium hydroxide, lactulose, sorbitol

• MOA: they create an osmotic force, pulling water into the stool and
creating additional bulk, in a manner analogous to that seen with the
bulk agents
lactulose
• Dose- 4-10 gm BD with plenty of water
• soft formed stools in 1-3 days
•S/E Flatulence Cramps, Nausea
•Use:
• Hepatic encephalopathy(reduces NH3 conc by 25-50%, lactulose
acidic product decrease pH of stool which ionizes ammonia
produced by bacteria in colon NH4+  not absorbed) Dose- 20g
TDS or more
Magnesium hydroxide
• Magnesium-containing laxatives may stimulate CCK release, which in turn leads to
increased fluid and electrolytes within the gut lumen and increased motility

• Magnesium hydroxide (milk of magnesia) is a commonly used osmotic laxative.

• It should not be used for prolonged periods in patients with renal insufficiency due
to the risk of hypermagnesemia.

• Dose- Mag sulphate- 5-15g,

Mag. Hypdroxide(8% W/W suspension”milk of magnesia”)- 30 ml

B. Balanced polyethylene glycol

• commonly used for complete colonic cleansing before GI endoscopic

procedures.
• These balanced, isotonic solutions contain an inert, nonabsorbable,
osmotically active sugar (PEG) with sodium sulfate, sodium chloride,
sodium bicarbonate, and potassium chloride.
• For treatment or prevention of chronic constipation, smaller doses of
PEG powder may be mixed with water or juices (17 g/8 oz) and
ingested daily.
4. STIMULANT LAXATIVES
• Powerful laxative
• Induces the bowel movement by direct stimulation of the enteric nervous
system and colonic electrolyte and fluid secretion.

• Stimulant laxatives are also known as irritant laxatives, and, as the name
suggests, they work by irritating the intestinal wall, which leads to an
accumulation of fluid and electrolytes and increased motility.
• Inhibits Na+ K+ ATPase at basolateral membraneous vilious cell
• Reduces Na+ water reabsorption
• Increase PG ,cAMP medicated secretion in crypt cell
• long-term use of cathartics could lead to dependence and destruction of
the myenteric plexus, resulting in colonic atony and dilation.

• Arthraquinone derivative: plants; Aloe, senna, cascara

• produce a bowel movement in 6–12 hours when given orally (before
bed time) and within 2 hours when given rectally.
• Can cause cramping, excessive purging, skin rashes occasionally
• Some patients taking anthraquinones may notice their urine coloured
brown (if acid) or red (if alkaline)
• Diphenylmethane derivatives: Bisacodyl ( tab / suppository
fom)
• It induces a bowel movement by getting activated in intestine by
deacetylation.
• Within 6–10 hours when given orally and 30–60 minutes when
taken rectally
• They may cause abdominal cramps, should be used only with
caution in pregnancy and never where intestinal obstruction is
suspected
5. CHLORIDE SECRETION ACTIVATOR
Lubiprostone
• Acts by stimulating the type 2 chloride channel (ClC-2) in the small
intestine.
• This increases chloride rich fluid secretion into the intestine, which
stimulates intestinal motility and shortens intestinal transit time
• CHRONIC CONSTIPATION: recommended dose 24mcg BD orally.
• CI: pregnancy
• Causes nausea due to delayed gastric emptying
Linaclotide and plecantide
• CI: pediatric age group
(mortality due to dehydration
in juvenile mice)
6. OPIOID RECEPTOR ANTAGONIST
• Constipation caused by opiate analgesics such as morphine is a result
of agonist effects on µ opiate receptors in the gut.
• Peripheral opiate µ antagonists are charged molecules that have
limited ability to cross into the brain; therefore they selectively block
the receptors that cause constipation without antagonizing the central
analgesic effects of the opiates.

• COMMERCIALLY AVAILABLE: Methylnaltrexone bromide and

Alvimopan
• Methylnaltrexone :opioid-induced constipation in patients receiving
palliative care for advanced illness who have had inadequate response to
other agents.
• It is administered as a subcutaneous injection (0.15 mg/ kg) every 2
days.

• Alvimopan is approved for short-term use to shorten the period of

postoperative ileus in hospitalized patients who have undergone small or
large bowel resection.
• Alvimopan (12 mg capsule) is administered orally within 5 hours before
surgery and twice daily after surgery until bowel function has recovered,
but for no more than 7 days
 7. SEROTONIN 5-HT4-RECEPTOR
AGONIST
• Tegaserod, cisapride,
prucalopride
Types of stools and latency of action of
purgative
Soft, formed faeces (take Semifluid stools (take 6- Watery evacuation
1-3 days) 8 hours) (within 1-3 hours)

Bulk forming Phenolphthalein Saline purgatives

Docusate Bisacodyl Castor oil

Liquid paraffin Sod. picosulfate

Lactulose Senna
 Before prescribing Laxative
• Laxatives should not be used in undiagnosed abdominal pain, colic or
vomiting
• Laxatives should be avoided if there is any question of pts. having an
intestinal obstruction, severe abd. pain, symptoms of appendicitis,
ulcerative colitis, or diverticulitis
• Laxative abuse from chronic use a problem, esp. with elderly
References

• Clinical Pharmacology, 9th edition, P.N. Bennett and M.J. Brown

• Basic and clinical pharmacology, katzung, 14th edition
• Applied pharmacology
THANK
YOU