Gastrointestinal Drugs

Prof. Dr. Muhammad Ashraf

Dean FBS
Professor of Pharmacology and Toxicology
UVAS, Lahore

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 Basic Anatomy and Physiology
 The term gastrointestinal (GI) tract describes a long,
muscular tube that begins at the mouth and ends at the
anus.
 Structures:
 Oral cavity
 Esophagus
 Stomach
 Small intestine
 Large intestine
 Structures vary from monogastric animals with simple
stomachs to ruminant animals with multichambered
forestomachs

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 Control Mechanisms of the GI Tract
 One control mechanism of the GI tract is the autonomic nervous
system (parasympathetic and sympathetic branches)
 Parasympathetic stimulation increases intestinal motility, increases
GI secretions, and relaxes sphincters
 Cholinergic drugs simulate these actions
 Anticholinergic drugs inhibit these actions
 Sympathetic stimulation decreases intestinal motility, decreases GI
secretions, and inhibits the action of sphincters
 Sympathetic nerves simulate these actions

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 Drugs Affecting the GI Tract
 1. Antisialogues
 2. Antidiarrheals
 3. Laxatives
 4. Emetics
 5. Antiemetics
 6. Antiulcer drugs
 7. Antifoaming drugs
 8. Prokinetic agents (which enhance gastrointestinal motility)
 9. Enzyme supplements

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 Drugs Affecting the GI Tract
 1. Antisialogues
 Drugs that decrease salivary flow
 Used to limit the flow of excess saliva, which often occurs
secondary to anesthetic drug use
 Examples include anticholinergics such as glycopyrrolate and atropine
 These drugs can also affect peristalsis because they are also used to treat
vomiting, diarrhea, and excess gastric secretion

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 Drugs Affecting the GI Tract
 2. Antidiarrheals
 Drugs that decrease peristalsis, thereby allowing fluid
absorption from the intestinal contents
 Examples:
 Anticholinergics
 Protectants/adsorbents
 Opiate-related agents
 Probiotics
 Metronidazole

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 Drugs Affecting the GI Tract
 Antidiarrheals (cont.)
 Anticholinergics are used to treat tenemus and vomiting
 Examples:
 Atropine
 Aminopentamide
 Isopropamide
 Propantheline
 Methscopolamine
 Side effects include dry mucous membranes, urine retention,
tachycardia, and constipation

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 Drugs Affecting the GI Tract
 Antidiarrheals (cont.)
 Protectants/adsorbents coat inflamed intestinal mucosa with a
protective layer (protectants) or bind bacteria and/or digestive
enzymes and/or toxins to protect intestinal mucosa from
damaging effects (adsorbents)
 Examples:
 Bismuth subsalicylate (bismuth + aspirin-like product)
 Kaolin/pectin
 Activated charcoal
 Side effects include constipation

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 Drugs Affecting the GI Tract
 Antidiarrheals (cont.)
 Opiate-related agents control diarrhea by decreasing both
intestinal secretions and the flow of feces and increasing
segmental contractions
 Examples:
 Diphenoxylate
 Loperamide (Imodium)
 Paregoric
 Lomotil (Diphenoxylate and Atropine)
 Side effects include CNS depression, ileus, urine retention,
bloat, and constipation

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 Drugs Affecting the GI Tract
 Antidiarrheals (cont.)
 Probiotics seed the GI tract with beneficial bacteria; use is based
on the theory that some forms of diarrhea are caused by
disruption of the normal bacterial flora of the GI tract
 Must be refrigerated to maintain the viability of the bacteria
 Examples:
 Plain yogurt with active cultures
 Variety of trade-name products

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 Drugs Affecting the GI Tract
 Antidiarrheals (cont.)
 A theory regarding the development of diarrhea is that
anaerobic bacteria may increase due to disruption of normal GI
flora
 One way to treat this is to use an antibiotic effective against
anaerobic bacteria
 Metronidazole is an example of an antibiotic used to treat
diarrhea

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 Drugs Affecting the GI Tract
 3. Laxatives
 A laxative loosens the bowel contents and encourages
evacuation of stool
 Laxatives help animals evacuate without excessive straining;
treat chronic constipation from nondietary causes and movable
intestinal blockages; and evacuate the GI tract before surgery,
radiography, or diagnostic procedures
 Cathartics are harsher laxatives; purgatives are harsh cathartics

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 Drugs Affecting the GI Tract
 Types of Laxatives
 Osmotic
 Pull water into the colon and increase water content in the feces, thereby
increasing bulk and stimulating peristalsis
 Are salts or saline product that may cause electrolyte imbalances if
absorbed systemically
 Examples include: lactulose, sodium phosphate with sodium biphosphate,
magnesium sulfate, magnesium hydroxide

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 Drugs Affecting the GI Tract
 Types of Laxatives (cont.)
 Stimulant
 Increase peristalsis by chemically irritating sensory nerve endings in the
intestinal mucosa
 Many are absorbed systemically and cause a variety of side effects
 Examples include bisacodyl, phenolphthalein, and castor oil

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 Drugs Affecting the GI Tract
 Types of Laxatives (cont.)
 Bulk-forming
 Substances that absorb water into the intestine, increase fecal bulk, and
stimulate peristalsis, resulting in large, soft stool production (which tends
to look normal)
 Are not systemically absorbed, so side effects are rare
 Examples include psyllium hydrophilic mucilloid "isabgol",
polycarbophil,and bran
 (Calcium Polycarbophil is a Bulk Forming Fiber Laxative . Bulk laxatives absorb liquid in
the intestines and swell to form a soft bulky stool)
 Psyllium hydrophilic mucilloid is a bulk-forming oral laxative used to
treat constipation and promote healthy bowel movements

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 Drugs Affecting the GI Tract
 Types of Laxatives (cont.)
 Emollients
 Can be stool softeners (reduce stool surface tension and reduce water
absorption through the colon), lubricants (facilitate the passage of fecal
material, increasing water retention in stool), or fecal wetting agents
(detergent-like drugs that permit easier penetration and mixing of fats
and fluid with the fecal mass)
 Examples include docusate sodium, docusate calcium, docusate
potassium, and petroleum products

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 Drugs Affecting the GI Tract
 4. Emetics
 Drugs that induce vomiting
 Used in the treatment of poisoning and drug overdose
 Vomiting should not be induced if caustic substances have been
ingested
 Always check with poison control prior to inducing vomiting
 Activated charcoal is given if emesis is contraindicated (it
absorbs many chemicals and drugs in the upper GI tract)

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 Drugs Affecting the GI Tract
 Emetics (cont.)
 Can be centrally acting (working on the CRTZ) or peripherally
acting (working on receptors locally)
 Centrally acting
 Apomorphine
 Xylazine
 Peripherally acting
 Ipecac syrup
 Home remedies

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 Drugs Affecting the GI Tract
 5. Antiemetics
 Drugs that control vomiting that help alleviate discomfort and
help control electrolyte balance
 Most are given parenterally, as the patient may vomit the
medication before it can be absorbed through the GI tract
 Examples:
 Phenothiazine derivatives
 Antihistamines
 Anticholinergics
 Procainamide derivatives
 Serotonin receptor antagonists

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 Drugs Affecting the GI Tract
 Antiemetics (cont.)
 Phenothiazine derivatives
 Inhibit dopamine in the chemoreceptor trigger zone, thus decreasing the
stimulation to vomit
 Side effects include hypotension and sedation
 Examples:
 Acepromazine
 Chlorpromazine
 Prochlorperzine
 Perphenazine

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 Drugs Affecting the GI Tract
 Antiemetics (cont.)
 Antihistamines
 Controls vomiting when the vomiting is due to motion sickness, vaccine
reactions, or inner ear problems
 Work by blocking input from the vestibular system to the CRTZ
 A side effect is sedation
 Examples:
 Trimethobenzamide
 Dimenhydrinate
 Diphenhydramine

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 Drugs Affecting the GI Tract
 Antiemetics (cont.)
 Anticholinergics
 Block acetylcholine peripherally, which decreases intestinal motility and
secretions
 May decrease gastric emptying (which may increase the tendency to
vomit)
 Side effects include dry mouth, constipation, urinary retention, and
tachycardia
 Examples:
 Aminopentamide
 Atropine
 Scopolamine
 Propantheline

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 Drugs Affecting the GI Tract
 Antiemetics (cont.)
 Procainamide derivatives
 Work centrally by blocking the CRTZ and peripherally by speeding
gastric emptying, strengthening cardiac sphincter tone, and increasing the
force of gastric contractions
 Should not be used in animals with GI obstructions, GI perforation, or GI
hemorrhage
 An example used in veterinary medicine is metoclopramide

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 Drugs Affecting the GI Tract
 Antiemetics (cont.)
 Serotonin receptor antagonists
 Work selectively on 5-HT3 receptors, which are located peripherally and
centrally
 Work on the theory that some chemicals cause vomiting because they
increase serotonin release from small intestinal cells
 Examples:
 Ondansetron
 Dolasetron

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 Drugs Affecting the GI Tract
 6. Antiulcer drugs
 Help prevent the formation of ulcers
 Categories include
 Antacids
 Histamine-2 receptor antagonists
 Mucosal protective drugs
 Prostaglandin analogs
 Proton pump inhibitors

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 Drugs Affecting the GI Tract
 Antiulcer drugs (cont.)
 Antacids
 Promote ulcer healing by neutralizing HCl and reducing pepsin activity
 Interact with other drugs
 By adsorption or binding the other drugs
 By increasing stomach pH
 By increasing urinary pH
 May be systemic or nonsystemic
 Examples:
 Systemic: sodium bicarbonate, calcium carbonate
 Nonsystemic: magnesium hydroxide, aluminum/magnesium hydroxide,
aluminum hydroxide

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 Drugs Affecting the GI Tract
 Antiulcer drugs (cont.)
 Histamine-2 receptor antagonists
 Prevent acid reflux by competitively blocking the H2 receptors of the
parietal cells in the stomach, thus reducing gastric acid secretion
 Examples:
 Cimetidine
 Ranitidine
 Famotidine
 Mucosal protective drugs
 Combine with protein to form an adherent substance that covers the
ulcer and protects it from stomach acid and pepsin
 An example is sucralfate

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 Drugs Affecting the GI Tract
 Antiulcer drugs (cont.)
 Prostaglandin analogs
 Suppress gastric secretions and increase mucus production in the GI tract
 An example is misoprostol, which is usually given to animals taking
NSAIDs
 Proton pump inhibitors
 Bind irreversibly to the H+-K+-ATPase enzyme on the surface of parietal
cells of the stomach; this inhibits hydrogen ion transport into the stomach
so that it cannot secrete HCl
 Examples:
 Omeprazole
 Lansoprazole

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 Drugs Affecting the GI Tract
 7. Antifoaming drugs
 Reduce or prevent the formation of foam
 Used in ruminants, whose rumens are subject to acute frothy
bloat
 Make this foam less stable, breaking it up to promote gas release
through belching
 Administered as solutions by stomach tube directly into the
forestomach
 Examples include poloxalene and polymerized methyl silicone

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 Drugs Affecting the GI Tract
 8. Prokinetic agents
 (Which enhance gastrointestinal motility by increasing the frequency of
contractions in the small intestine or making them stronger, but without
disrupting their rhythm).
 Increase the motility of parts of the GI tract to enhance
movement of material through it
 Types of prokinetic agents are parasympathomimetics,
dopaminergic antagonists, and serotonergic agents
 Parasympathomimetic agents include
 Acetylcholinesterase inhibitors, which compete with ACh for
acetylcholinesterase, resulting in increased intestinal tone and salivation
 An example is neostigmine
 Cholinergics, which make a precursor to acetylcholine
 An example is dexpanthenol

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 Drugs Affecting the GI Tract
 Prokinetic agents (cont.)
 Dopaminergic agents stimulate gastroesophageal sphincter,
stomach, and intestinal motility by sensitizing tissues to the
action of the neurotransmitter ACh
 Examples include metoclopramide and domperidone
 Serotonergic agents stimulate motility of the gastroesophageal
sphincter, stomach, small intestine, and colon
 An example is cisapride

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 Drugs Affecting the GI Tract
 9. Enzyme supplements
 Pancreatic enzymes must be supplemented in the diet when the
pancreas is not functioning properly (as in pancreatic exocrine
insufficiency)
 Pancrealipase contains primarily lipase, but also contains
amylase and protease
 Can be irritating to the skin on contact and to nasal passages
upon inhalation

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  Q. Select the one best answer
1. Serotonergic agent used to increase intestinal motility
 a. Cisapride b. loperidol c. atropine d. diphenhydaramine e. domperidone

2. Proton pump inhibitor used to decrease HCl secretion

 a. Omeprazole b. metaclopramide c. dexpanthenol d. poloxalene e. aluminum hydroxide

3. Anticholenergic used as antiemetic

a. Dolasetron b. Cisapride c. Metaclopramide d. Lansoprazole e. Aminopentamide

4. Centrally acting Emetic

a. Apomorphine b. Ipecac syrup c. Chlorpromazine d. Ondansetron e. metoclopramide

5. Mucosal protective drug used for peptic ulcer

a. Sucralfate b. Cimetadine c. aluminum hydroxide d. misoprostol e. Lansoprazole

6. Opiate related antidiarrheal agent

a. Diphenoxylate b. Isopropamide c. Metronidazole d. Bismuth subsalicylate e. bisacodyl

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