Chapter 11Chapter 11

Gastrointestinal DrugsGastrointestinal Drugs

Autonomic Nervous Autonomic Nervous SystemSystem

Sympathetic = “Fight or Flight”

Parasympathetic = EAT TURKEY & SLEEP IT OFF

Control Mechanisms of the GI Control Mechanisms of the GI TractTract

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 DisordersGastrointestinal DisordersAmong the most common complains

in veterinary medicineUnderlying 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 Drugs Affecting the GI TractTract

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 Glycopyrrolate (Robinul) and AtropineAtropine

AntidiarrhealsAntidiarrheals

◦Antidiarrheals are drugs that decrease peristalsis, thereby allowing fluid absorption from the intestinal contents

◦Examples: Anticholinergics Protectants/adsorbents Opiate-related agents Probiotics Metronidazole

AntidiarrhealsAntidiarrheals◦ 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

AntidiarrhealsAntidiarrhealsProtectants & 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

AntidiarrhealsAntidiarrhealsOpiate-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

AntidiarrhealsAntidiarrhealsProbiotics

◦ 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

ProbioticsProbiotics

AntidiarrhealsAntidiarrhealsMetronidazole

◦ 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

MetronidazoleMetronidazole

LaxativesLaxatives

◦ 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

◦ CatharticsCathartics are harsher laxatives; purgativespurgatives are harsh cathartics

LaxativesLaxativesTypes of Laxatives include:

◦Osmotic◦Stimulant◦Bulk-forming◦Emolliments

LaxativesLaxativesOsmotic

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

LaxativesLaxativesStimulant

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

LaxativesLaxatives

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

LaxativesLaxativesEmollients

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

AntiemeticsAntiemetics 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

AntiemeticsAntiemeticsVomiting 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

AntiemeticsAntiemeticsPhenothiazine 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

AntiemeticsAntiemeticsAntihistamines

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

AntiemeticsAntiemeticsAnticholinergics

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

AntiemeticsAntiemeticsProcainamide 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

AntiemeticsAntiemeticsSerotonin 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®)Maropitant (Cerenia®)

AntiemeticsAntiemeticsNeurokinin 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 (Cerenia®)◦ Used to prevent acute vomiting and motion

sickness◦ Side effects include:

Pain at the injection site, hypersalivation, and diarrhea

EmeticsEmetics 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)

EmeticsEmetics

◦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 EmesisInducing Emesis

Apomorphine

Xylazine

Antiulcer DrugsAntiulcer DrugsAntiulcer drugs

◦Help prevent the formation of ulcers◦Categories include

Antacids Histamine-2 receptor antagonists Mucosal protective drugs Prostaglandin analogs Proton pump inhibitors

Antiulcer DrugsAntiulcer DrugsAntacids

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 DrugsAntiulcer DrugsHistamine-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 DrugsAntiulcer DrugsMucosal 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 DrugsAntiulcer DrugsProstaglandin 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

Antifoaming AgentsAntifoaming 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 EnhancingMotility EnhancingProkinetic 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 AgentsProkinetic AgentsParasympathomimetic 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 AgentsProkinetic AgentsDopaminergic 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

Enzyme SupplementsEnzyme 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 Appetite-Stimulating DrugsDrugsSerotonin antagonist antihistamines

◦ Promote appetite by inhibition at the serotoninergic receptors which control satiety

◦ Side effects include sedation and dry mouthBenzodiazepines

◦ 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

Appetite Stimulating Appetite Stimulating DrugsDrugsGlucocorticoids

◦ 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

Appetite Stimulating Appetite Stimulating DrugsDrugsProgestins

◦ Used to stimulate appetite and promote weight gain in anorectic cats and dogs

◦ Side effects include behavioral changes, endometritis, and mammary enlargement

Appetite SuppressionAppetite SuppressionDirlotapide (Slentrol®)

◦ Drug for management of obesity in dogs◦ Side effects include vomiting, diarrhea,

lethargy, and anorexia