Drug for constipation and enema

1. CONSTIPATION AND ITS
MANAGEMENT
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3. CONSTIPATION
• Water normally accounts for 70%–85% of total stool weight.
• Net stool fluid content reflects a balance between
✓ luminal input (ingestion of fluids) & luminally directed secretion
of water and electrolytes
✓And output (absorption) along the length of the GI tract.
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4. • Hormonal imbalances
• Neurogenic disorders
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6. MANAGEMENT OF CONSTIPATION
• Majority of people do not need laxatives…..MOST self-prescribe
• For most people, intermittent constipation is best prevented with:
➢High-fiber diet
➢Adequate fluid intake
➢Regular exercise
➢Heeding of nature’s call
Those who don’t respond to the above should undergo medical
evaluation be4 initiating long-term laxative Tx.
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7. Prevalence
• Common in the
-elderly
-patients with advanced, progressive illnesses
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8. DRUGS FOR CONSTIPATION
• Usually called laxatives, cathartics, purgatives, aperients, evacuants
• Often are used interchangeably
• Laxation: the evacuation of formed fecal material from the rectum
• Catharsis: The evacuation of unformed, usually watery, fecal
material from the entire colon
• Most of the commonly used agents promote laxation, but some are
actually cathartics that act as laxatives at low doses
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9. Classification of Laxatives
➢Luminally active agents
• Hydrophilic colloids; bulk-forming agents (bran, psyllium, etc.)
• Osmotic agents (nonabsorbable inorganic salts or sugars)
• Stool-wetting agents (surfactants) and emollients (docusate,
mineral oil)
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10. ➢ Nonspecific stimulants or irritants (with effects on fluid
secretion and motility)
• Diphenylmethanes (bisacodyl), Anthraquinones (senna and
cascara)
• Castor oil
➢Prokinetic agents (acting primarily on motility)
• 5HT4 receptor agonists, Dopamine receptor antagonists, Motilides
(erythromycin)
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11. LAXATIVES
Classification according to mechanism of action
✓Bulk-forming Laxatives
✓Stool Surfactant Agents (Softeners)
✓Osmotic Laxatives
✓Stimulant Laxatives
✓Chloride Channel Activator
✓Opioid Receptor Antagonists
✓Serotonin 5-HT4 -Receptor Agonists
✓Guanylate Cyclase C Agonists
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13. 1. BULK-FORMING LAXATIVES
MOA: Indigestible, hydrophilic colloids that absorb water, forming a
bulky, emollient gel that distends the colon and promotes peristalsis.
EXAMPLES
• Natural plant products e.g. psyllium, methylcellulose, ispaghula, agar
• Synthetic fibers e.g. polycarbophil
Onset of action…2-3days
NOTE: Bacterial digestion of plant fibers within the colon may lead to
↑sed bloating & flatus.
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14. 2. STOOL SURFACTANT AGENTS (SOFTENERS/emollient laxatives)
MOA: soften stool material, permitting water and lipids to penetrate.
May be admin orally or rectally
EXAMPLES
1. Docusate (oral or enema)- commonly prescribed in hospitalized patients to
prevent constipation and minimize straining.
• Glycerin (suppository)-absorbed when given orally but acts as a hygroscopic
agent and lubricant when given rectally.
• The resultant water retention stimulates peristalsis & usually produces a bowel
movement in less than an hour
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15. 3. Lubricant laxative eg Mineral oil/ Liquid paraffin , olive oil
Mineral oil: clear, viscous oil that lubricates fecal material, retarding water
absorption from stool, softens it and makes it easier to move thru the
intestines
• may be mixed with juices (coz its not palatable)
• used to prevent & treat fecal impaction in young children & debilitated
adults
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16. CAUTION: Aspiration can result in a severe lipid pneumonitis.
Long-term use can impair absorption of fat-soluble vitamins (A, D, E, K).
Liquid paraffin not recommended—risk of aspiration & lipoid pneumonia.
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17. 4.OSMOTIC LAXATIVES
• Are soluble but non absorbable cpds that result in ↑sed stool liquidity
due to an obligate ↑ se in fecal fluid.
• Non absorbable Sugars or Salts- TX of acute constipation or the
prevention of chronic constipation
EXAMPLES
➢Saline Laxatives. Laxatives containing magnesium cations or phosphate
anions
• Include:-magnesium sulfate, magnesium hydroxide, magnesium citrate,
and sodium phosphate
MOA: cathartic action of magnesium salts is believed to result from
osmotic water retention, which then stimulates peristalsis
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18. • Magnesium hydroxide (milk of magnesia)- should not be used for
prolonged periods in patients with renal insufficiency due to the
risk of hypermagnesemia
❖Phosphate salts
• Are better absorbed than Mg2+-based agents
• Need to be given in larger doses to induce catharsis.
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19. • Associated with acute phosphate nephropathy, hence are not
recommended & should be completely avoided in patients at risk
➢Nondigestible Sugars and Alcohols (Sorbitol, mannitol & lactulose)
MOA: Are hydrolyzed in the colon to short-chain fatty acids, which
stimulate colonic propulsive motility by osmotically drawing water into
the lumen
- metabolized by colonic bacteria, producing severe flatus & cramps
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20. • High doses of osmotically active agents produce prompt bowel evacuation
(purgation) within 1–3 hrs
• most commonly used purgatives are magnesium citrate & sodium phosphate
❖Balanced Polyethylene Glycol
Lavage solutions contain an inert, nonabsorbable, osmotically active sugar (PEG)
with sodium sulfate, sodium chloride, sodium bicarbonate, potassium chloride.
➢Used for complete colonic cleansing be4 GI endoscopic procedures
➢smaller doses of PEG powder may be mixed with water or juices ingested daily
for Tx or prevention of chronic constipation
❑does not produce significant cramps or flatus
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21. 5. STIMULANT/IRRITANT LAXATIVES (CATHARTICS) eg castor oil
Induce bowel movements through a number of mxm
✓direct stimulation of the ENS
✓Colonic electrolyte and fluid secretion.
Note: Long-term use of cathartics could lead to dependence & destruction
of the myenteric plexus, resulting in colonic atony & dilation
EXAMPLES:
Anthraquinone Derivatives e.g Aloe, senna, cascara sagrada
• poorly absorbed & after hydrolysis in the colon
• Produce movement in 6–12 hrs when given orally & in 2 hrs rectally
• Chronic use leads to brown pigmentation of the colon “melanosis coli”
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22. Diphenylmethane Derivatives e.g Bisacodyl
• Available in tablet & suppository formulations
✓Tx of acute & chronic constipation.
✓Also used in conjunction with PEG solutions for colonic cleansing prior
to colonoscopy
• Induces bowel mov’t within 6–10 hrs when given orally & 30–60 min
when taken rectally
• Minimal systemic absorption (safe for acute & long-term use).
❖Phenolphthalein, another agent in this class, removed from the market
owing to concerns about possible cardiac toxicity.
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23. 6. CHLORIDE CHANNEL ACTIVATOR e.g Lubiprostone
A prostanoic acid derivative used in chronic constipation & irritable bowel
syndrome (IBS) with predominant constipation.
MOA: Acts by stimulating the type 2 chloride channel (ClC-2) in the small
intestine, increasing Cl-rich fluid secretion into the intestine, which
stimulates intestinal motility & shortens intestinal transit time
• bind to the EP4 receptor for PGE2, a GPCR that couples to Gs, activating
adenylyl cyclase and leading to enhanced apical Cl- conductance
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24. • category C for pregnancy (increased fetal loss in guinea pigs)
• May cause nausea in up to 30% of patients due to delayed gastric
emptying.
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25. 7. Prokinetic agents
SEROTONIN 5-HT 4 -RECEPTOR AGONISTS
• Stimulation of 5-HT 4 receptors on the presynaptic terminal of submucosal
intrinsic primary afferent nerves enhances release of their NT, including
calcitonin gene-related peptide, which stimulate 2nd -order enteric neurons to
promote peristaltic reflex
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26. • Cisapride & Tegaserod-5-HT 4 partial agonist-REMOVED on market
increased incidence of serious CVS events
• Prucalopride- high-affinity 5-HT 4 agonist that is available in Europe
TX of chronic constipation in women
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27. 7. OPIOID RECEPTOR ANTAGONISTS
• Do not readily cross the BBB
• Inhibit peripheral μ-opioid receptors without impacting analgesic effects
within the CNS
❑Methylnaltrexone-approved for TX of opioid-induced constipation in
patients receiving palliative care for advanced illness who have had
inadequate response to other agents
• Given SQ (0.15 mg/kg) every 2 days
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28. ❑Alvimopan (oral 12mg capsules)
-approved for short-term use to shorten the period of postoperative ileus in
hospitalized patients who have undergone small or large bowel resection.
• Possible CVS toxicity-currently restricted to short-term use in hospitalized
patients only
NALDEMEDINE-Peripherally restricted opioid antagonist
• Tx of opioid-induced constipation in adult patients with chronic noncancer
pain; dose, 0.2 mg/d, orally
Naloxegol-----composed of the MOR antagonist naloxone conjugated to a PEG
polymer
• Approved for the treatment of opioid-induced constipation
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29. 8. Guanylate Cyclase C Agonists eg linaclotide
• 14–amino acid peptide agonist of the membrane-spanning GC-C
• In the intestinal epithelium, GC-C is activatedphysiologically by guanylin and
uroguanylin, pathologically by heat-stable bacterial toxins that cause diarrhea
MOA:- Activation of GC-C results in increased synthesis of cGMP, resulting in
enhanced CL- and bicarbonate secretion into the intestinal lumen, leading in
turn to water secretion and enhanced motility.
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30. • Used in constipation-predominant IBS and chronic constipation in adults
• Side effects include diarrhea (which can be serious), gas, abdominal pain, and headaches.
• Contraindicated in children under 6 years old and is not recommended for older children
Plecanatide.
• 6-amino acid peptide related to uroguanylin; it has essentially the same mechanism of action
as linaclotide.
• Approved for the treatment of chronic idiopathic constipation in adults
• Read about use of misoprostol in constipation
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31. ENEMAS
• Are aqueous or oily solutions or suspensions or o/w type emulsions,
which are intended to introduce into rectum for cleansing,
therapeutic or diagnostic purposes
• They induce bowel movements by softening hard stool & stimulating
colonic muscle contraction in response to rectal & colonic distention
• can be used for fecal impaction
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32. Classification of enemas
✓Retention enemas e.g. Oil retention enema (120 mL vegetable oil)
✓Cleansing enemas e.g. Hypotonic enemas e.g. tap water enema,
Hypertonic enemas e.g. salt-containing enemas (phosphate and
soapsuds enemas) and Isotonic e.g. saline enemas
-Used in constipation, prior to a colonoscopy or other medical
examination
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33. ✓Carminative/anti-spasmodic enema (contains MgSO4, water plus glycerin):-
used to remove the gaseous accumulation/flatus in abdomen
✓Return flow enema/harris flush-removing painful flatus eg after
abdominal surgery
• Enemas should be used cautiously in patients with a history of bowel
stricture or recent lower bowel surgery & in immunocompromised
patients.
• READ MORE………………………….
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34. Enema administration
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