Chapter 8 Drugs Used in Gastrointestinal System Disorders

. Diphenoxylate is a synthetic narcotic agent

(Class V) that is structurally similar to meperidine. Atropine sulfate is added to commercial preparations to discourage substance abuse.

Antifoaming agents act as surfactants

(reduce surface tension) and cause bubbles to break down so that gas can be relieved by eructation or by the stomach tube. These products are given orally.

Parietal cell

A cell located in the gastric mucosa that secretes hydrochloric acid.

Adsorbent

A drug that inhibits gastrointestinal absorption of drugs, toxins, or chemicals by attracting and holding them to its surface.

Motilin

A hormone secreted by cells in the duodenal mucosa that causes contraction of intestinal smooth muscle.

Dentifrice

A preparation for cleansing teeth that is available in a powder, paste, or liquid.

These drugs increase the amount of acetylcholine available to bind smooth muscle receptors.

Acetylcholinesterase Inhibitors

Cholinergic

Activated by or transmitted through acetylcholine; also called parasympathomimetic. Cholinergic drugs increase activity in the gastrointestinal tract.

Chemoreceptor trigger zone

An area in the brain that activates the vomiting center when stimulated by toxic substances in the blood

Vomiting center

An area in the medulla that may be stimulated by the chemoreceptor trigger zone, the cerebrum, or peripheral receptors to induce vomiting.

These include treatment of gastric ulcer, gastritis, esophagitis, and hyperphosphatemia in small animals. In ruminants, they are used to treat rumen overload.

Antacids

is used primarily for induction of vomiting in dogs. It is considered by many to be the emetic of choice for dogs. Its use in cats is controversial and possibly is contraindicated. Xylazine, which is safer than apomorphine, is effective as an emetic in most cats.

Apomorphine

Anticholinergic

Blocking nerve impulse transmission through the parasympathetic nervous system; also called parasympatholytic. Anticholinergic drugs may be used for the treatment of diarrhea or vomiting.

Regurgitation

Casting up of undigested or semidigested (ruminant) foodstuff from the esophagus or rumen

is used as an antiemetic in dogs and cats. It is more effective in dogs than in cats.

Chlorpromazine

is used for the treatment or prevention of gastric, abomasal, or duodenal ulcers; hypersecretory conditions of the stomach; esophagitis; gastric reflux; and experimentally as an immunomodulator.

Cimetidine

Uses include the treatment of constipation in cats and gastroesophageal reflux and gastrointestinal stasis in dogs, cats, and horses.

Cisapride

Bismuth subsalicylate is a compound found in products such

Corrective Suspension and Pepto-Bismol. Bismuth subsalicylate is converted to bismuth carbonate and salicylate in the small intestine. The bismuth has a coating and antibacterial effect, and the salicylate (an aspirin-like compound) has an antiinflammatory effect and reduces secretion by inhibiting prostaglandins (Boothe, 2012).

Melena

Dark or black stools that result from blood staining. Bleeding has occurred in the anterior part of the gastrointestinal tract.

Clinical uses are similar to those of cimetidine and ranitidine.

Famotidine

The opiates are used in

GI therapy for the control of diarrhea.

Antiulcer Medications

Gastric ulcers may occur in animals for various reasons, including stress, metabolic disease, gastric hyperacidity, and drug therapy (e.g., corticosteroids or nonsteroidal antiinflammatory agents) (Hall, 2001). Anorexia, hematemesis, pain, and melena are common signs of gastric ulcer.

The dosage is 1 teaspoon (5 mL) per 5 pounds of body weight not to exceed 45 mL

Hydrogen Peroxide

These agents are used for the relief of constipation.

Laxatives

These include treatment of constipation and fecal impaction.

Lubricants

is used as an antiemetic for parvoviral enteritis, uremic vomiting, and vomiting associated with chemotherapy. It is also used to treat gastric motility disorders

Metoclopramide

Uses may include increasing lower esophageal sphincter pressure, accelerating gastric emptying, and facilitating intestinal transit time.

Motilin-Like Drugs

Uses include the prevention and treatment of vomiting in dogs resulting from motion sickness or other causes.

NK-1 antagonists block

Even though nizatidine is an H2 receptor blocker, it is used primarily in small animal medicine as a prokinetic agent for the treatment of constipation and delayed gastric emptying

Nizatidine

H2 Receptor Antagonists

One of the primary stimuli for secretion of hydrochloric acid by gastric parietal cells is activation of H2 receptors by histamine. By blocking H2 receptors, H2 receptor antagonists reduce the release of hydrochloric acid, thus decreasing irritation of the eroded mucosa and promoting healing

This product is used to treat pancreatic exocrine insufficiency.

Pancrelipase

These include control of vomiting (prochlorperazine alone) in dogs and cats and treatment of vomiting, gastroenteritis, diarrhea, spastic colitis, and motion sickness (combination product).

Prochlorperazine

These agents are used to control diarrhea and act as adsorbents.

Protectants/Adsorbents

These agents are used to treat gastric or duodenal ulcers and esophagitis and may be useful in treating parietal hypersecretion associated with gastrinoma and mastocytosis (DeNovo, 2002). Omeprazole has a veterinary-approved label for the treatment and prevention of recurrence of gastric ulcers in horses and foals

Proton Pump Inhibitors

Clinical uses are identical to those of cimetidine.

Ranitidine

The autonomic nervous system

Stimulation of the parasympathetic portion of the ANS increases intestinal motility and tone, increases intestinal secretions, and stimulates relaxation of sphincters. Drugs that mimic parasympathetic stimulation (i.e., cholinergic or parasympathomimetic) cause similar results. Anticholinergic, or parasympatholytic, drugs inhibit these ANS actions. • Stimulation of the sympathetic branch of the ANS decreases intestinal motility and tone, decreases intestinal secretions, and inhibits sphincters. • Stimulation of various intrinsic receptors in the GI tract, such as the myenteric plexus (stretch receptor), also may increase peristaltic activity. Some physiologists consider the intrinsic receptors (myenteric plexus and Meissner's plexus) to be a third portion of the ANS called the enteric nervous system (

Clinical uses include the treatment of hard, dry feces in small animals; impaction in horses; and occasionally digestive upset in cattle.

Surfactants/Stool Softeners

Acetylcholinesterase Inhibitors

These agents are used to treat rumen atony, to enhance gastric emptying (ranitidine), to stimulate peristalsis, to empty the bladder of large animals, and to aid in the diagnosis of myasthenia gravis (neostigmine) in dogs. They also may be used to treat curare overdose.

Proton Pump Inhibitors

These agents bind irreversibly at the secretory surface of the parietal cell to the enzyme Na-K-ATPase. This enzyme is responsible for "pumping" hydrogen ions into the stomach against a concentration gradient. When bound in this way, the enzyme is inactivated and the cell is unable to secrete acid until a new enzyme is synthesized.

Direct Cholinergics

These include postoperative treatment of ileus—or retention of flatus or feces—and equine colic (without obstruction).

Prokinetic/stimulant drugs increase the motility of

a part or parts of the gastrointestinal tract and by doing this enhance the transit of material through the tract. Several classes of drugs, including dopaminergic antagonists, serotonergic drugs, motilin-like drugs, direct cholinergics, and acetylcholinesterase inhibitors, have the ability to enhance gastrointestinal motility. As was previously noted, some H2 receptor antagonists exhibit prokinetic activity

Phenothiazine-derivative antiemetics

act centrally by blocking dopamine receptors in the CRTZ and possibly by direct inhibition of the vomiting center. These agents are in widespread use. They are very useful in preventing motion sickness in dogs and cats but may be less effective against irritant emetics

Doxirobe is placed in the periodontal pocket

after dental cleansing with the use of a cannula. Upon contact with the aqueous environment, the product coagulates and releases doxycycline for several weeks.

A 3% solution of hydrogen peroxid

an be used orally to induce vomiting. Vomiting is induced by a direct irritant effect on the oropharynx and stomach lining.

Laxatives are substances that loosen bowel

and encourage their evacuation

Metronidazole is a synthetic

antibacterial and antiprotozoal agent. This drug is prohibited from use in food-producing animals.

Cyproheptadine

antihistamine used as an appetite stimulant primarily in cats

Antiemetics

are drugs that are used to prevent or control vomiting. The use of antiemetics is a form of symptomatic treatment because these drugs do not necessarily correct the underlying cause of the vomiting.

Narcotic analgesics (opiates)

are effective agents in the control of diarrhea because of their ability to (1) increase segmental contractions, (2) decrease intestinal secretions, and (3) enhance intestinal absorption. Many clinicians consider opiates to be the drugs of choice for the control of diarrhea in dogs.

Serotonin receptors

are found on vagal nerve terminals and in the CRTZ (Plumb, 2011). Blockade of these 5-HT3 receptors causes antiemetic activity.

Substances such as histamine, serotonin, and prostaglandin

are released from specialized cells of the GI tract. Histamine attaches to H2 receptors in gastric parietal cells to cause increased release of hydrochloric acid in the stomach. The influences of serotonin and prostaglandin are not as well defined.

Metoclopramide is used for treatment of

astroesophageal reflux and delayed gastric emptying, for stimulation of the gastrointestinal tract in foals, and for gastrointestinal motility disorders in dogs and cats.

Irritants act by irritating the gut wall

ausing stimulation of GI smooth muscle and increased peristalsis. These drugs are seldom used in veterinary medicine. This category includes several agents that are sometimes used in the treatment of constipation in humans. • Bisacodyl (Dulcolax) • Castor oil

Cimetidine

competitively inhibits histamine at H2 receptors of gastric parietal cells, thereby reducing hydrochloric acid secretion by these cells. Cimetidine, the least potent of the H2 receptors, must be given 3 to 4 times daily to be effective

Emetics

drugs that induce vomiting. are administered to animals that have ingested toxins, but they must be used carefully to avoid serious complications.

Anticholinergics and antispasmodics have been widely used in veterinary medicine

for the treatment of diarrhea. Because hypomotility rather than hypermotility is now considered to be associated with most cases of diarrhea, anticholinergics and antispasmodics should be used with caution for the treatment of diarrhea. A few commercial antidiarrheal preparations contain an anticholinergic plus a CNS depressant.

Antifoaming agents are used to treat

frothy bloat in ruminants. In this condition, gas bubbles form and become trapped in the rumen fluid as a result of consumption of wheat pasture or legumes, such as alfalfa or clover. The trapped bubbles cause a form of bloat that cannot be relieved by usual means.

Lubricants are typically oils or other hydrocarbon derivatives

hat soften the fecal mass and make it easier to move through the GI tract.

Dopaminergic antagonists used as prokinetics

in veterinary medicine include metoclopramide and domperidone

Metoclopramide

is a derivative of procainamide and has central and peripheral antiemetic activities. Centrally, it blocks dopamine receptors in the CRTZ, whereas peripherally, it increases gastric contraction, speeds gastric emptying, and strengthens cardiac sphincter tone. Metoclopramide has a limited influence on GI secretions. This drug has a short half-life and may have to be administered often or in a continuous drip in severe cases of vomiting

Apomorphine

is a morphine derivative that stimulates dopamine receptors in the CRTZ, which then activates the vomiting center. This drug is poorly absorbed after oral administration and is therefore usually administered topically in the conjunctival sac or parenterally.

Segmentation

is a periodic, repeating pattern of intestinal constrictions that serves to mix and churn the contents.

Prochlorperazine

is a phenothiazine derivative agent with moderate sedative effects and strong antiemetic effects. The approved form of this drug is a combination product that contains an anticholinergic agent (Darbazine). Prochlorperazine is available singly as Compazine (human label).

Chlorpromazine

is a phenothiazine-derivative tranquilizer that has little popularity as a tranquilizer in veterinary medicine and is more often used as an antiemetic.

Misoprostol

is a prostaglandin E1 analogue that directly inhibits the parietal cell from secreting hydrogen ions into the stomach. It also protects the gastric mucosa by increasing the production of mucus and bicarbonate.

Peristalsis

is a wave of contractions that propels contents along the digestive tract

Ranitidine

is also an H2 receptor antagonist that competitively inhibits histamine at parietal cell receptors and reduces hydrochloric acid secretion. Ranitidine has little effect on hepatic microenzymes and is unlikely to cause drug interactions. Ranitidine is the H2 receptor antagonist preferred by many clinicians because of its greater potency (five times that of cimetidine) and greater duration of action. Ranitidine also has prokinetic activity in that it promotes gastric emptying

Nizatidine

is an H2 receptor antagonist that also has prokinetic activity, similar to ranitidine.

Famotidine

is an H2 receptor antagonist that is considerably more potent than cimetidine. It is administered once a day and may have fewer drug interactions than cimetidine or ranitidine.

Sucralfate

is the only gastromucosal protectant in common use in veterinary medicine. This drug is a disaccharide that, when administered orally, forms a pastelike substance in the stomach that binds to the surfaces of gastric ulcers.

Diarrhea

is the passage of loose or liquid stools, often with increased frequency

Hydrogen peroxide

is the primary agent. Other locally acting emetics that have been used with various degrees of effectiveness include mustard and water, syrup of ipecac, and warm salt water.

Saline or hyperosmotic laxatives contain

magnesium or phosphate anions that are very poorly absorbed from the GI tract. It generally is believed that these anions hold water in the tract osmotically.

Diazepam

medication that produces a transient appetite stimulation when given intravenously

Loperamide is a synthetic narcotic that is available in a

nonprescription preparation. Loperamide poorly penetrates the CNS in cats and is acceptable in this species

Antibiotics are not routinely used in the treatment

of GI tract disease in small animals because these agents may destroy normal inhabitants of the GI tract and allow pathogenic bacteria (e.g., Salmonella species, C. jejuni, C. perfringens, C. difficile, Helicobacter, and others) to grow on the mucosal surface.

Bulk-producing agents are used for relief

of constipation and for relief of some types of impaction (sand primarily) in horses.

Metronidazole is used for treatment

of giardiasis, trichomoniasis, balantidiasis, plasmacytic/lymphocytic enteritis, ulcerative colitis, hepatic encephalopathy, and anaerobic infection in dogs. It is also used to treat giardiasis and anaerobic infections in cats and anaerobic infections in horses. Dosage Form

Antiinflammatory agents are used in the treatment

of idiopathic inflammatory bowel disease in animals. Increased numbers of lymphocytes, macrophages, plasma cells, or eosinophils in the intestinal wall characterize these diseases. Treatment often involves the use of hypoallergenic diets and antiinflammatory agents.

Sucralfate is used in the treatment

of oral, esophageal, gastric, and duodenal ulcers.

Hydrogen peroxide is used for the induction

of vomiting in dogs, cats, pigs, and ferrets.

Pancrelipase is a product that contains

pancreatic enzymes that aid in the digestion of fats, proteins, and carbohydrates. The powder that contains the enzymes is mixed with the animal's food, which is allowed to stand for 15 to 20 minutes before feeding.

Bulk-producing agents are often indigestible

plant materials (e.g., cellulose or hemicellulose) that act by absorbing water and swelling to increase the bulk of intestinal contents, thereby stimulating peristalsis.

Protectants/Adsorbents

roducts in this category may have protectant or adsorbent qualities in the GI tract. The coating action of these drugs protects inflamed mucosa from further irritation.

Antihistamines

s are most effective as antiemetics in dogs and cats when vomiting is a result of motion sickness or inner ear abnormalities. Antihistamines inhibit vomiting at the level of the CRTZ through H1 blockade. All antihistamines may cause sedation.

Probiotics are used to treat

stress-related GI upset, antibiotic-associated diarrhea, diarrhea associated with dietary change, inflammatory bowel disease, gingival disease, and some conditions associated with other body systems.

Probiotics are beneficial live microbe

that are administered orally to animals to support intestinal and overall health.

Cisapride is the serotonergic prokinetic

that is used in veterinary medicine. Cisapride stimulates motility of the proximal and distal gastrointestinal tract, including the gastroesophageal sphincter, stomach, small intestine, and colon

NK-1 antagonists block

the binding of substance P (a neurotransmitter involved in vomiting) to NK-1 receptors in the CRTZ.

Vomiting is forceful ejection of the contents of the stomach,

the contents of the proximal small intestine, through the mouth

xylazine

the label indicates that it induces vomiting within 3 to 5 minutes in cats and occasionally in dogs. Some clinicians consider xylazine to be the agent of choice for inducing vomiting in cats. Normal precautions should be followed regarding administration of this product.

nticholinergics/antispasmodics are used for

the treatment of diarrhea.

Prostaglandin E1 analogues are used primarily

to prevent or treat gastric ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs).

Erythromycin has been used by veterinarians

to treat bacterial and mycoplasmal infections for many years. This drug has been shown to stimulate gastrointestinal motility by mimicking the effect of the hormone motilin

Dirlotapide is a selective microsomal triglyceride

transfer protein inhibitor that blocks the assembly and release of lipoprotein particles into the bloodstream in dogs.

Antacids

used in veterinary medicine are (relatively) nonabsorbable salts of aluminium, calcium, or magnesium. Antacids are used to decrease hydrochloric acid levels in the stomach as an aid in the treatment of gastric ulcers. In ruminants, antacids such as magnesium hydroxide are used to treat rumen acidosis (rumen overload syndrome) and are used as a laxative. Antacids also may be used in patients with renal failure to bind with (chelate) intestinal phosphorus and reduce hyperphosphatemia.

Emesis

vomiting

Hematemesis

vomiting blood

Surfactants reduce surface tension and allow

water to penetrate GI contents, thus softening the stool. They also may increase intestinal secretions

. GI hormones such as gastrin, secretin, and cholecystokinin

when released from intestinal cells, exert control over many functions such as gastric secretion, emptying of the gallbladder, and gastric emptying.