Transcript Control Mechanisms of the GI Tract

Chapter 11
Gastrointestinal Drugs
Sympathetic
=
“Fight or Flight”
Parasympathetic =
EAT TURKEY & SLEEP IT OFF
Autonomic Nervous System
Control Mechanisms of the GI Tract
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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
Gastrointestinal Disorders
Among the most common complains in
veterinary medicine
 Underlying causes include:

◦ Infectious sources, dietary excess, adverse drug
effects, systemic disease

These disorders result in clinical signs such as:
◦ Diarrhea, constipation, vomiting, bloat, ulcer
development, (generally associated with pain)
Drugs Affecting the GI Tract
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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
Glycopyrrolate (Robinul) and
Atropine
Antidiarrheals
◦ Antidiarrheals are drugs that decrease
peristalsis, thereby allowing fluid absorption
from the intestinal contents
◦ Examples:
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Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Metronidazole
Antidiarrheals
◦ Anticholinergics are used to treat tenemus and
vomiting
◦ Examples:
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Atropine
Aminopentamide
Isopropamide
Propantheline
Methscopolamine
◦ Side effects include dry mucous membranes, urine
retention, tachycardia, and constipation
Antidiarrheals

Protectants & Adsorbents
◦ Protectants coat inflamed intestinal mucosa with a
protective layer
◦ Adsorbents bind bacteria and/or digestive enzymes
and/or toxins to protect intestinal mucosa from
damaging effects
◦ Examples:
 Bismuth subsalicylate (bismuth + aspirin-like product)
 Kaolin/pectin
 Activated charcoal
◦ Side effects include constipation
Antidiarrheals

Opiate-related agents
◦ Narcotic analgesics control diarrhea by decreasing
both intestinal secretions and the flow of feces and
increasing segmental contractions
◦ Examples:
 Diphenoxylate
 Loperamide
 Paregoric
◦ Side effects include CNS depression, ileus, urine
retention, bloat, and constipation
Antidiarrheals
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Probiotics
◦ 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
Probiotics
Antidiarrheals
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Metronidazole
◦ 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
Metronidazole
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
Laxatives
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Types of Laxatives include:
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Osmotic
Stimulant
Bulk-forming
Emolliments
Laxatives
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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
Laxatives
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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
Laxatives
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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,
polycarbophil,and bran
Laxatives
 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
Antiemetics
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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:
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Phenothiazine derivatives
Antihistamines
Anticholinergics
Procainamide derivatives
Serotonin receptor antagonists
Antiemetics
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Vomiting has many causes including:
◦ Viral and bacterial infections, dietary indiscretion,
food intolerance, surgery, pain, or other drugs
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The vomiting center of the brain have many
inputs that tell it to activate including:
◦ Equilibrium changes in the ear, responses due to pain
or fear, intracranial pressure changes, vagus nerve
stimulation in the GI tract, and activity in the
chemoreceptor trigger zone
Antiemetics
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Phenothiazine derivatives
 Inhibit dopamine in the chemoreceptor trigger zone, thus
decreasing the stimulation to vomit
 Side effects include hypotension and sedation
 Examples:
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Acepromazine
Chlorpromazine
Prochlorperazine
Perphenazine
Antiemetics
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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
Antiemetics
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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
 Propantheline
Antiemetics
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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
Antiemetics
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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
Maropitant (Cerenia®)
Antiemetics
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Neurokinin receptor antagonists
◦ Work on NK1 receptors located in the center of the
brain
◦ Work by inhibiting substance P, the key
neurotransmitter involved in vomiting
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Maropitant citrate (Cerenia®)
◦ Used to prevent acute vomiting and motion sickness
◦ Side effects include:
 Pain at the injection site, hypersalivation, and diarrhea
Emetics
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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)
Emetics
◦ 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
Inducing Emesis
Apomorphine
Xylazine
Antiulcer Drugs
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Antiulcer drugs
◦ Help prevent the formation of ulcers
◦ Categories include
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Antacids
Histamine-2 receptor antagonists
Mucosal protective drugs
Prostaglandin analogs
Proton pump inhibitors
Antiulcer Drugs
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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
Antiulcer Drugs
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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 (Tagament®)
 Ranitidine (Zantac®)
 Famotidine (Pepcid®)
Antiulcer Drugs
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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
Antiulcer Drugs
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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
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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
Antifoaming Agents
◦ 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
Motility Enhancing
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Prokinetic agents
◦ Increase the motility of parts of the GI tract to
enhance movement of material through it
◦ Types of prokinetic agents are:
 parasympathomimetics
 dopaminergic antagonists
 serotonergic agents
Prokinetic Agents
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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
Prokinetic Agents
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Dopaminergic agents stimulate
gastroesophageal sphincter, stomach, and
intestinal motility by sensitizing tissues to
the action of the neurotransmitter ACh
 Examples include metoclopramide and domeridone
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Serotonergic agents stimulate motility of
the gastroesophageal sphincter, stomach,
small intestine, and colon
 An example is cisapride
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
Appetite-Stimulating Drugs
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Serotonin antagonist antihistamines
◦ Promote appetite by inhibition at the serotoninergic receptors
which control satiety
◦ Side effects include sedation and dry mouth
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Benzodiazepines
◦ Effective appetite stimulants in cats but not dogs
◦ Side effects include sedation and ataxia
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Tetracyclic antidepressants
◦ Stimulate appetite by antagonizing alpha2-receptors
◦ Side effects include sedation, vocalization
Appetite Stimulating Drugs
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Glucocorticoids
◦ Stimulate steroid-induced euphoria which stimulates
appetite
◦ Side effects include polydipsia, polyuria, dull haircoat,
weight gain, and behavioral changes
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Anabolic steroids
◦ Stimulate hematopoiesis, appetite, and weight gain
◦ Side effects include hepatotoxicity, masculinization,
and early closure of growth plate in young animals
Appetite Stimulating Drugs
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Progestins
◦ Used to stimulate appetite and promote weight gain
in anorectic cats and dogs
◦ Side effects include behavioral changes, endometritis,
and mammary enlargement
Appetite Suppression
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Dirlotapide (Slentrol®)
◦ Drug for management of obesity in dogs
◦ Side effects include vomiting, diarrhea, lethargy, and
anorexia