Download Cengage Learning

Chapter 11
Gastrointestinal Drugs
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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, or pain
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• Antidiarrheals
– Drugs that decrease peristalsis, thereby
allowing fluid absorption from the intestinal
contents
– Examples:
•
•
•
•
•
Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Metronidazole
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
• Paregoric
– Side effects include CNS depression, ileus, urine
retention, bloat, and constipation
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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,
polycarbophil,and bran
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• Vomiting has many causes including:
– Viral and bacterial infections, dietary indiscretion, food
intolerance, surgery, pain, or other drugs
• 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
Copyright © 2011 Delmar, Cengage Learning
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
Prochlorperazine
Perphenazine
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
– Propantheline
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
• Maropitant citrate
– Used to prevent acute vomiting and motion sickness
– Side effects include:
• Pain at the injection site, pre-travel vomiting and
hypersalivation, and diarrhea
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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)
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• Antiulcer drugs
– Help prevent the formation of ulcers
– Categories include
•
•
•
•
•
Antacids
Histamine-2 receptor antagonists
Mucosal protective drugs
Prostaglandin analogs
Proton pump inhibitors
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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,
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
Copyright © 2011 Delmar, Cengage Learning
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 domeridone
– Serotonergic agents stimulate motility of the
gastroesophageal sphincter, stomach, small intestine,
and colon
• An example is cisapride
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
• 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
• • Refer to Table 11-1 in your textbook
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
Appetite Altering Drugs
• Serotonin antagonist antihistamines
– Promote appetite by inhibition at the serotoninergic
receptors which control satiety
– Side effects include sedation and dry mouth
• Benzodiazepines
– Effective appetite stimulants in cats but not dogs
– Side effects include sedation and ataxia
• Tetracyclic antidepressants
– Stimulate appetite by antagonizing alpha2-receptors
– Side effects include sedation, vocalization
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
Appetite Altering Drugs
• Glucocorticoids
– Stimulate steroid-induced euphoria which stimulates
appetite
– Side effects include polydipsia, polyuria, dull haircoat,
weight gain, and behavioral changes
• Anabolic steroids
– Stimulate hematopoiesis, appetite, and weight gain
– Side effects include hepatotoxicity, masculinization,
and early closure of growth plate in young animals
Copyright © 2011 Delmar, Cengage Learning
Drugs Affecting the GI Tract
Appetite Altering Drugs
• Progestins
– Used to stimulate appetite and promote weight gain in
anorectic cats and dogs
– Side effects include behavioral changes, endometritis,
and mammary enlargement
• Dirlotapide
– Drug for management of obesity in dogs
– Side effects include vomiting, diarrhea, lethargy, and
anorexia
Copyright © 2011 Delmar, Cengage Learning
Dental Prophylaxis and Treatment
• Refer to Table 11-1 in your textbook
Copyright © 2011 Delmar, Cengage Learning