antiemetics, anti-diarrheals and drugs for constipation and irritable bowel syndrome

1. Antiemetics, Anti-Diarrheals ,Drugs for
Constipation and Irritable Bowel
Syndrome
By - Kuldeep Kumar
M.Pharm (Pharmacology)
2nd Semester

2. Antiemetic Drugs
 Nausea and vomiting (emesis) are mechanisms to
remove toxic or noxious substances after ingestion.
However, they also may occur in response to motion,
pregnancy, or disease.
 Vomiting is controlled by the vomiting center in the
medulla, which receives inputs from the nearby
chemoreceptor trigger zone (CTZ), the vestibular
apparatus of the inner ear, the cerebral cortex, and the
GI tract.

3. The Vomiting Reflex
 The vomiting reflex begins with a single retrograde peristaltic contraction
beginning in the middle of the small intestine that propels intestinal
contents through a relaxed gastroduodenal junction into the stomach.
 Inspiration occurs against a closed glottis, lowering intraesophageal
pressure. The duodenum and antrum contract to prevent movement of
chyme back into the small intestine.
 The abdominal muscles then forcibly contract (Valsalva maneuver),
increasing intra-abdominal pressure which creates more pressure in the
stomach than in the esophagus. This forces gastric contents into the
esophagus.
 The larynx and hyoid bone are drawn forward, decreasing the tone of the
upper esophageal sphincter (UES) leading to the gastric and esophageal
contents being expelled via the oral cavity.

4. NK1 Antagonists
 Aprepitant
 Mechanism of action. Aprepitant is a neurokinin-1-receptor
(substance P) antagonist that blocks that action of neurokinin-1
in the brain.
 Pharmacokinetics – Given orally – Extensively metabolized
in the liver (via cytochrome P-450 3A4 [CYP3A4])
 Uses – Chemotherapy-induced nausea and vomiting
 Side effects – Constipation, diarrhea, and loss of appetite –
Headache, hiccups, and fatigue
 Drug interactions. Interactions may occur due to induction of
cytochrome P-450 enzymes in the liver.

5. Cannabinoid Agonists
 Dronabinol
 This agent is a derivative of marijuana.
 Mechanism of action. Dronabinol acts on the vomiting center of the brain
to prevent emesis, but the mechanism is unknown.
 Pharmacokinetics – Given orally
 Uses – Chemotherapy-induced emesis, which is unresponsive to other drugs
 Side effects - Sympathomimetic activity that leads to heart palpitations and
tachycardia
- Marijuana - like central nervous system (CNS) effects, such as
euphoria, somnolence, dizziness, and disturbances in thinking
- Abdominal pain, nausea, and vomiting
- Xerostomia (dry mouth) is very common.

6. Antidiarrheal Agents
 Antidiarrheal therapy aims to prevent the dehydration and
electrolyte imbalance that can quickly occur in severe
diarrhea, as well as preventing excessive bowel movements.
 Note: Antibacterial agents are useful only if bacteria are the
cause of the diarrhea (which is uncommon). They cause
depletion of the normal intestinal bacterial flora, which, in
turn, may cause proliferation of pathogenic bacteria, leading
to diarrhea.

7. Adsorbents
 Bismuth Subsalicylate, Kaolin, and Pectin
– Bismuth subsalicylate
– Kaolin (hydrated aluminum silicate)
– Pectin (a purified carbohydrate from acid extracts of apples or the
rinds of citrus fruits)
 Mechanism of action. These agents absorb bacterial toxins and fluid
in the gut.
 Pharmacokinetics – Bismuth subsalicylate is given as chewable
tablets or in an aqueous suspension.
– Kaolin is often given in a mixture with pectin.
 Uses – Diarrhea and dysentery
 Side effects. These drugs are not absorbed, so they do not have
systemic side effects. Constipation may occur.

8. Opioids
 Mechanism of action. These agents decrease propulsion and
peristalsis. GI contents are delayed in passage, allowing time for
feces to become desiccated. This further retards passage through
the colon.
– Opioids are effective in acute diarrheal states, but they should not
be used for enteric infections.
– Opium alkaloids are effective for controlling severe diarrhea or
dysentery, but with chronic therapy, there is a risk of dependence.
 Paregoric - Paregoric is a camphorated tincture of opium.
 Uses – Infantile diarrhea

9. Codeine and/or Morphine
 These are purified opium alkaloids.
 Pharmacokinetics. They exert a local action in the GI tract.
 Diphenoxylate. Diphenoxylate is a congener of meperidine. It is
often given in combination with atropine.
 Side effects. High or chronic doses lead to euphoria and physical
dependence.
 Loperamide. Loperamide is a derivative of haloperidol that
resembles meperidine. This agent appears to be as effective as
diphenoxylate, with few side effects reported.
 Uses – Prophylaxis and treatment of travelers’ diarrhea
– Irritable bowel syndrome (IBS)

10. Constipation
 difficult or infrequent passage of stool
 S/S: abdominal bloating, headaches, sense of rectal fullness
 Causes:
 Insufficient dietary fiber
 lack of exercise
 Medications (anticholinergic, antacids, narcotics)
 Organic problems- intestinal obstruction, IBS, tumor etc.
 Treatment :
Non pharmacologic :
 increase fluid and fiber intake
 exercise regularly
 bowel training ti increase regularity

11.  Pharmacologic :
Laxatives - stimulate defection, should not be taken if nausea, vomiting, or
abdominal pain is present
1. Bulk-forming laxatives
MOA: natural or synthetic polysaccharide that absorb water to soften stool and
increase bulk, which stimulates peristalsis
 slow onset of action (12-24 hrs, 72 hrs) thus preventive
 take with 8 oz of water
 C/I obstruction bowel lesion, intestinal strictures , Crohn's disease
 Natural bulk-forming laxatives
 Psyllium (Metamucil, Fiberall, Konsyl-D, Perdium Fiber Granules), Malt soup
extract (Maltsupex)
 Synthetic bulk-forming laxatives
 Methylcellulose, Polycarbophil (Ca Polycarbophil impairs Tetracycline absorption)

12. 2. Saline & Osmotic Laxatives
 MOA: Creates an osmotic gradient pulling water into the small and
large intestines, stimulates the activity of cholecystokinin-
pancreozymin which increases the secretion of fluids into the GI tract
 Onset of oral: 3-6 hrs: rectal - 5-30 minutes
 Saline laxatives - sodium and magnesium salts
 Should not be used in patients with HPN, CHF, & renal impairment
 Magnesium citrate, Magnesium hydroxide, Magnesium sulfate,
Sodium
 Osmotis laxatives -
 Glycerin - rectal burning
 Lactulose - decrease blood ammonia levels in hepatic
 Encephalopathy, S/E flatulence & cramping
 Sorbitol - nonabsorbable sugar
 Polyethylene glycol

13. 3. Stimulant laxatives
 MOA: stimulate intestinal motility and increase secretion of fluid into
the bowel
 Onset of action of oral: 6-10 hrs; rectal 30-60 minutes
 Chronic use can lead to cathartic colon (should not be used for more
than 1 week)
 S/E: abdominal cramping
 Anthraquinone glycoside - melanoma coli
 Sennosides - most potent
 Cascara sagrada
 Casanthranol - mild stimulant laxative
 Bisacodyl (Dulcolax) - diphenylmethane derivative, enteric-coated
 Castor oil-onset: 2-6 hrs; works in the small intestine which C/I in
pregnant women

14. 4. Emollient laxatives
 MOA: act as surfactants by allowing absorption of water into stool
 Slow onset of action: 24-72 hrs
 Should not be used with mineral oil because it facilitates systemic
absorption of mineral oil leading to hepatotoxicity
 Docusate sodium
 Docusate calcium
 Docusate potassium
5. Lubricant laxative (Mineral oil)
 MOA: works at the colon to increase water retention in the stool
 onset of action: 6-8 hrs
 May cause anal seepage, lipid pneumonotis, decrease vit. A,D,E,K
absorption

15. Irritable Bowel Syndrome (IBS)
 IBS is a chronic idiopathic condition. Symptoms include
abdominal pain, bloating, and cramps, which are associated with
bowel habit alteration in the form of constipation or diarrhea.
 Treatment is guided by the symptoms and their severity. Mild IBS
may respond to dietary changes. Drugs may be called for in
patients with moderate to severe symptoms.
 Antispasmodics, such as hyoscyamine and dicyclomine, laxatives
(docusate, bisacodyl, senna, or osmotic agents) and loperamide are
standard.
 In severe cases with diarrhea, alosetron, a potent and selective
antagonist of the 5- HT3 receptor that decreases intestinal motility
and pain may be used with caution, as it can lead to severe
constipation.

16.  pain, cramping, gassiness, constipation and/ordiarrhea
 symptoms appear after eating or during stress and result from
abnormal motility
 Treatment
 Alosetron - a serotonin antagonist which blocks serotonin in the
GI tract thereby reducing the abdominal cramping, urgency, and
diarrhea associated with IBS
 Antispasmodic - hyoscyamine, dicyclomine
 Bulk-forming agents -psyllium
 Antiflatulent - simethicone
 Loperamide