Drugs used in Gastrointestinal system disorders
Drugs used in Gastrointestinal system disorders
Vomiting:
Is forceful ejection of the contents of the stomach, and sometimes the contents of proximal small intestine, through the mouth. It is intiated by activation of vomiting (emetic) center in the medulla of the brain, which is connected by nerve to the chemoreceptor trigger zone(CTZ), cerebral cortex and peripheral receptors in the inner ear, pharynx, GIT, urinary system and heart. The disease of these organs in addition to pain, excitement, fear, drugs, uremia ketonemia endotoxemia and others.
Emetics:
Are drugs that induce vomiting, used for animals that have ingested toxic materials. These drugs should not be used (contraindicated)in animals that do not normally vomit such as rabbits, some rodents and horses, comatose animals, seizure, depressed pharyngeal reflexes, shock, dyspnea, ingestion of strong acid, alkali or other substances
Emetics are classified according to their site of action into two groups:
1- Centrally acting emetics:
These drugs acting on the CTZ such as apomorphine and xylazine.
a- Apomorphine:
- Is a morphine derivative that stimulate dopamine receptors in the CTZ, which then activate vomiting center.
- Poorly absorbed orally.
- Administered topically in the conjuncival sac or parentrally.
- Used to induce vomiting in dogs.
- Contraindicated in cat.
- Side effects: protracted vomiting, restlessness and depression.
b- Xylazine:Used to induce vomiting in cats.
2- locally acting emetics: these drugs act on peripheral receptors such as
Ipecac :
- obtained from plant root.
- contains alkaloids that irritate the gastric mucosa and induce vomiting within 10-30min.
- It may also stimulate CTZ.
- Used to induce vomiting in dogs and cats.
- Side effects include cardiotoxicity (inhigh dose), lacrimation and salivation.
Antiemetics:
drugs that are used to prevent vomiting, usually given parentrally.
1- phenothiazine derivatives
- include chlorpromazine and prochlorperazine.
- antiemetics that act by blocking dopamine receptors in the CTZ.
- May inhibit the vomiting center directly.
- Useful in preventing motion sickness in dogs and cats.
- Side effects include hypotesion and sedation.
2- procainamide derivatives:
Metaclopramide:
- acts centrally by blocking dopamine receptors in the CTZ and peripherally by increasing gastric contraction, speeds gastric empting and strengthens cardiac shincter tone.
- Indicated as antiemetic in paroviral eneritis, uremic vomiting and vomiting associated with chemotherapy. Also used for tretment of gastric motility disorders.
3- Antihistamines:
- include trimethobenzamide (used in dogs only), dimenhydrinate, diphenhydramine, meclizine and promethazine.
- They used maily in motion sickness in addition to allergic condition.
4- Anticholinergics:
- include: atropine, aminopentamide and propantheline which act peripherally.
- Atropine and aminopentamide also block the CTZ.
- Used in treatment of abdominal spasm and associated nausea, vomiting and diarrhea.
- Side effects include dry mucous membranes, constipation, tachycardia and urinary retention.
5- Butyrophenones:
- include droperidol, haloperidole and pimozide.
- Group of tranqulizers block CTZ and vomiting center.
- Rarly used in vet. Medicine.
6- Serotonin receptor antagonists:
- include ondansetron and others.
- Used as antiemetic during chemotherapy.
7- NK-1 receptor antagonists:
- maropitant blocks the binding of substance P to NK-1 receptors in CTZ.
- Used as antiemetic in dogs.
- Side effects include diarrhea, bloody stool, anorexia and otitis.
Antiulcers drugs:
Gastric ulcers may occur due to stress, metabolic disease, gastric hyperacidity and drug therapy (corticosteroids and NSAIDs). Anorexia, hematemesis, pain and melena are common sings of gastric ulcer. Antiulcer drugs include:
1- H2 receptor antagonists:
- include cimetidine, ranitidine, fomatidine and rizantidine.
- All these drug act by blocking H2 receptor on gastric parietal cells reduce acid secretion,thus decreasing irritation of the mucosa and promoting healing.
- Cimetidine is the prodrug, less potent, has microsomal enzyme inhibition action and antiandrogenic effect ( gynecomastia and galactorrhea).
- Ranitidine and others are being more potent, less toxic, less side effects, has a weaker inhibitory effect on hepatic drug metabolism and do not have antiandrogenic effect.
- These drugs are used for treatment or prevention of gastric, abomasal, or duodenal ulcers, hypersecretory conditions of the stomach, esophagitis, gastric reflux.
2- Proton pump inhibitors:
- include omeprazole and lansoprazole.
- These drugs inhibit irreversibly Na-K-ATPase at the secretory surface of the parietal cell which is responsible for pumping H+ into the stomach.
- Indication include gastric ulcer, duodenal ulcer, esophagitis, hypersecretion associated with gastrinoma and mastocytosis.
- Side effects include constipation, sedation, pancreatitis and CNS effects.
3- Antacid:
- these are nonabsorbable salts of aluminium, calcium or magnesium.
- Used to decrease acid levels in stomach as an aid in the treatment of gastric ulcers.
- In ruminants, antacid (MgOH) used to treat rumen acidosis and as laxative.
- Antacid bind with intestinal phophorus and reduce hyperphosphatemia.
- Uses include gastric ulcer, gastritis, esophagitis and hyperphosphatemia.
- Side effects include constipation or diarrhea.
4- gastromucosal protectants:
- Sucralfate is disaccharide that when administered orally, forms a paste-like substance in the stomach that binds to the surfaces of gastric ulcers. This paste-like material forms a barrier over the ulcer to protect it from further damage and to promote healing.
- Used in treatment of oral, esophageal, gastric and duodenal ulcers.
5- prostaglandin E-1 analogs:
- Misoprostol is PGE1 analog that directly inhibits the parietal cell from secreting H+ into the stomach and increasing production of mucus and bicarbonate.
- Used in treatment and prevention of gastric ulcer associated with the use of NSAIDs.
- Side effects include diarrhea, vomiting, flatulence and abdominal pain.
Diarrhea:
- It is the passage of loose or liquid stools with increased frequency.
- The mechanism include hypersecretion, increased permeability, osmotic overload, altered intestinal motility.
- Causes of diarrhea includeparasitism, bacterial endotoxins for different bacteria, viruses
- Diarrhea result in electrolyte and fluid losses, dehydration, acidosis, weakness and anorexia.
Antidiarrheal drugs:
1- narcotic analgesics (Opiates):
- mechanism by increase segmental contractions, decrease intestinal secretions and enhance intestinal absorption.
- Used in treatment of diarrhea in dogs and calves, but not in cats and horses due to CNS stimulation.
- Side effects include constipation, ileus, sedation and CNS excitement.
2- Anticholinergics (Antispasmodic):
- include aminopentamide, methscopolamine, hyoscyamine, propantheline.
- these drugs decrease intestinal motility.
- side effects include dry mouth, constipation, urine retention and blurred vision.
3- protectants (adsorbents):
- The coating action of these drugs protects inflamed mucosa from further irritation.
- Their adsorbent activity binds bacteria or their toxins to protect against the harmful effects of these organisms.
- kaolin and pectin are used in protectant compounds.
- Bismuth subsalicylate is another protectants which is converted to bismuth carbonate and salicylate in the small intestine. The bismuth has a coating and antibacterial effect and the salicylate has an antiinflammatory effect and reduces secretion by inhibiting PGs.
- Activated charcoal is an adsorbent that is used primarily to treat poisoning.
- uses of these drugs to control diarrhea and act as adsorbent.
Laxatives:
- are substances that loosen bowel contents and encourage their evacuation.
- Laxatives with strong effect called cathartics or purgative. They include:
1- saline (hyperosmotic agents):
- contain magnesium o phosphate anions that are very poorly absorbed from the GIT.
- These anions hold water in the tract osmotically, and inceased water in the GIT result in softens the stool and stimulates strech receptors to enhance peistalsis.
- These agents used to relief constipation.
- Side effects include cramping or nausea, overuse may result in hyperphosphatemia or hypocalcemia especially in cats.
2- bulk- producing agents:
- these are indigestible plant materials (cellulose or hemicellulose) that act by absorbing water and swelling to increase the bulk of intestinal ontents, thereby stimulating peristalsis.
- Indication include constipation and some types of impaction in horses.
- Side effects are rare.
3- Lubruicants:
- These are typically oils or other hydrocarbon derivatives thet soften the fecal mass and make it easier to move through the GIT.
- Used for constipation and fecal impaction.
- Side effecst are minimal.
4- Surfactants (stool softeners):
- these agents reduce surface tension and allow water to pentrate GIT centents, thus softening the stool.
- Used in treatment of constipation and impaction in horses.
5- Irritants:
- These agents act by irritating the cauing stimulation of GIT smooth muscle and increased peristalsis.
- Rarely used in animals. Used for tratment of constipation in humans.
- These include bisacodyl, costor oil and emodin.
Gastrointestinal prokinetics (stimulants):
These drugs increase the motility of GIT, thus enhance the transit of material through the tract. These including several classes of drugs:
1- Dopaminergic antagonists:
- include metclopramide and domperidone.
- These agents stimulate motility of gastroesophageal sphincter and small intestine
- Used in treatment of gastroesophageal reflex, delayed gastric emptying, stimulation of GIT in foals and for GIT motility disorders in dogs and cats.
- Side effects include behavioral changes in dogs, cats and horses.
2- Serotenergic drugs:
Cisapride:
- is the serotenergic prokinetic that is used frequently in vet. Medicine.
- It stimulate motility of the GIT including gastroesophageal sphincter, stomach, small intestine and colon.
- Used for contipation in cats, gastroesophageal reflex and gastrointestinal stasis in dogs cats and horses.
- Side effects include diarrhea and abdominal pain.
3- Motilin-like drugs:
Erythromycin :
- this drug shown to stimulate GIT motility by mimicking the effect of motilin hormone.
- It stimulates motility of esophageal sphincter, stomach and smaal intestine.
- Uses may include increasing lowe esophageal shincter pressure, accelerating gastric emptying in addition to uses in bacterial and mycoplasmal infections.
- Side effects include anorexia, vomiting, dirrhea and abdominal pain.
4- Direct cholinergics:
Dexpanthenol:
- acts directly on cholinergic receptors.
- Uese include pstoperative tretment of ileus or retention of flatus or feces and equine colic (without obstruction).
- Side effects include cramping and diarrhea.
5- Acetylcholinestrase inhibitors:
Neostigmine:
- These drugs increase the amount of Ach available to bind smooth muscle receptors.
- Indications include treatment of rumen atony, enhance gastric emptying, stimulation of peristalsis, emptying the bladders of large animals, diagnosis of myasthenia gravis in dogs and may be used to treat curare overdose.
- Side effects are cholinergic and include nausea, vomiting, diarrhea, drooling, sweating, lacrimation and bradycardia.
Digestive enzymes:
Pancrelipase is a product that contains pancreatic enzymes that aid in the digestion of fats, proteins and carbohydrates. The powdre that contain the enzyme is mixed with the animal’s food. High doses may cause cramping, nausea and diarrhea.
Antibiotics:
- include metronidazole, amoxicillin, clavamox and tylosin.
- These are not routinely used in the treatment of GIT disease in small animals because these agents ma destroy normal inhabitants of GIT and allow pathogenic bacteria to grow on the mucosal surface.
- Indication of antibiotics include bloody diarrhea or signs of sepsis.
Metronidazole:
- is synthetic antibacterial and antiprotozoal agent.
- Indications include treatment of giardiasis, trichomoniasis, balantidiasis, lymphocyctic enteritis, ulcerative colitis, hepatic encephalopathy and anaerobic infection in dogs. Treatment of giardiasis and anaerobic infection in cats. Treatment of anaerobic infection in horses.
- Side effects include anorexia, hepatotoxicity, neutropenia, vomiting and diarrhea.
Antiinflammatory agents:
- include prednisone, azathioprine, sulfasalazine and olsalazine.
- used in the treatment of idiopathic inflammatory bowel disease in animals, which characterized by increasing numbersof lymphocytes, macrophages, plasma cells or eosinophils in the intestinal wall.
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.
- Used for treatment of frothy bloat in ruminants.
- Side effects are rare.
Weight-loss products:
Dirlotapide:
Is a selective microsomal triglyceride transfer protein inhibitor that blocks the assembly and release of lipoprotein particles into the blood stream in dogs. It is indicated for the manegment of obesity in dogs. Side effects include vomiting, diarrhea, lethergy, anorexia, constipation and dehydration.
Probiotics: are substances that competitively inhibit enteropathogens. They are used to treat diarrhea, inflammatory bowel disease and food allergy.
Appetite stimulants:
- These agents stimulating animal to eat to maintain optimal functioning of immune system and othe organ function.
- Cats who do not eat adequately for a period of time may develop a fatty liver syndrome that can be life threatening.
- Thease drugs include diazepam, alprazolam and cyproheptadine.
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