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Drugs Acting on the Gastrointestinal tract GIT related disorders Other disorders In appetence Appetite stimulants Different drugs Diarrhoea Acids Antidiarhoeal Antiacids Indigestion Constipation Laxatives and cathartics Digestants Vomiting/Emesis Emetics/antiemetics Introduction Most of the GIT disorders are related with motility Non specific treatment of GIT disorders may be useful by - Correction of fluid and electrolyte balance - Rest of the GIT - Diet modification - Provision of nutritional support - Alleviation of visceral pain Appetite stimulants Benzodiazepines Cyproheptadine Glucorcorticoids Bitters Zinc Appetite stimulants Benzodiazepines - Diazepam - Oxazepam Mode of action- Stimulation of GABA Clinical use – Most in cats, less in Horses, dogs and goats Admn – Oral Cyproheptadine It suppreses the satiety center in the brain by acting as serotonin and Histamine (H1) antagonist Clinica use – in cats and human, not in dogs Adverse effects – Excitement and aggressive behavior in some cats Glucocorticoids Examples - Prednisolone - Dexamethazone Mode of action – may be induce euphoria Adverse effects – Immunosuppression and gastric ulcers may result Bitters These are plant derived compounds containing alkaloids such as Nux vomica Mode of action – They stimulate salivation Zinc It is essential for the sensation of taste; therefore zinc supplements may increase appetite in zinc-deficient animals Anorexigenic substances For effective anorexigenic substances include amphetamine - member of the group phenylalkylamines with central and peripheral sympathomimetic properties. Its mechanism of action is mainly in the fact that it enhances the release of nerve endings of norepinephrine and dopamine, and inhibits the reuptake of them. At the same time stimulates the central adrenergic receptors and dopamine receptors, leading to inhibition of the hunger center. In addition, amphetamine has a stimulating effect on the cerebral cortex, and perhaps secondarily inhibits the hunger center. However, due to the fact that amphetamine refers to the active psychoactive drugs and has a pronounced peripheral sympathomimetic properties when applied arise anxiety, insomnia, tachycardia, increased blood pressure may develop physical drug dependence. Therefore, as an amphetamine like drugs are not used. A series of analogues of amphetamine (fenilalkilamina derivatives) with more selective anorexigenic effects, for example Fepranon (amfepranon). Pharmacologically similar to it fenaminom, but inferior to him in ability to reduce appetite. The mechanism anoreksigennogo fepranona effect is similar to that of amphetamine, but it is less stimulates the central nervous system. In addition, it is not as pronounced Adrenomimeticalkie peripheral effects. Use of the drug combined with a decrease in food intake. Enter Fepranon inside, usually for 30-60 minutes before eating. To avoid sleep disturbance ¬ taking it out in the first half of the day. Treatment should be under the supervision of a physician. When using fepranona possible side effects of the cardiovascular system (tachycardia, hypertension, arrhythmias) and CNS (anxiety, sleep disturbance). Marked the development of addiction and physical drug dependence. The drug is contraindicated in severe arterial hypertension, coronary heart disease, cerebrovascular disorders, with glaucoma ¬ ME, thyrotoxicosis, nerve diseases, leading to increased impact ¬ wake CNS and convulsions. Anorexigenic property is possessed and back ¬ selective inhibitors of neuronal uptake of serotonin. However, previously known drugs in this group due to the side effects are no longer used. In Examples include fluoxetine, used primarily as anti ¬ tidepressanta. However, it has severe and anorexigenic effect. Sibutramine (Meridia) is an anorexigenic agent ingibiruyushim reverse neuronal uptake of norepinephrine, serotonin and dopamine. Pony ¬ zhaet concentration in serum uric acid, a beneficial effect on blood lipids. Quickly and well (~ 77%) is absorbed from the digestive tract. Most of the drug is metabolized in the first pass through the liver. Of formed metabolites have anoreksigennoy activity. Sibutramine and Me ¬ metabolite is largely bound to plasma proteins blood was isolated ¬ are in the kidneys. Of the side effects observed pressor effect, tachycardia, ¬ solution violation of sleep, headache, CNS stimulation, constipation, etc. ANTACIDS They include - Acid secretion inhibitors - Proton pump inhibitors - Locally acting antacids - Gastric protectants Acid secretion inhibitors Histamine (H2) blockers - Cimetidine - Ranitidine Mode of action – H2 stimulates the proton (acid) pump in parietal cells. H2 blockers block the H2 receptors hence decrease HCL secretion Proton pump inhibitors Example Omeprazole Mode of action – they inhibit H+-K+ATPase hence reduce hydrogen secretion Locally acting antacids They include - Aluminum salts (Aluminum hydroxide, Aluminum carbonate, Aluminum silicate) - Magnesium salts (Magnesium oxide (milk of magnesia), Magnesium tricilicate - They act by neutralizing gastric HCL Gastric protective Example is Sucralfate This is a sucrose sulfate-aluminum hydroxide complex Mode of action – it polymerizes to a viscous gel. The sulfate groups bind to proteins in ulcerated tissue and protect ulcers from acids and pepsin DIGESTANTS Introduction Definition - Digestants are a group of drugs used to promote the process of digestion in the gastrointestinal tract They include - Pancrelipase - Bile acids and salts Pancrelipase It consists of pancreatic enzymes (e.g. lipase, amylase, trypsin) Clinical use – Used to treat exocrine pancreatic insufficiency in dogs, cats and birds Bile acids and salts They include; - Bile acids (e.g. cholic acid, chenodeoxycholic acid) - Semisynthetic bile acid derivatives (e.g. dehydrocholic acid) - Sodium salts of bile acids Mode of action – they stimulate choleresis (bile flow) EMETICS They include - Centrally acting emetics Apomorphine Xylazine - Peripherally acting emetics Sodium Chloride Syrup of ipecac (from Ipecacuanha) Copper sulfate, zinc sulfate, hydrogen peroxide ANTI EMETICS They include - Antidopaminergic agents - Antihistamines - Anticholinergic agents - Miscellaneous antiemetics Antidopaminergic agents Phenothiazine drugs Acepromazine Chlorpromazine Promazine Prochlorperazine Metoclopramide Butyrophenones Droperidol Haloperidol Antihistamines Dimenhydrinate Diphenhydramine Promethazine Anticholinergic agents Aminopentamide Propantheline Isopropamide Darbazine (isopropamide plus prochlorperazine) Miscellaneous antiemetics Intestinal protectants and adsorbents (kaolin, pectin, bismuth salts) Locally acting gastric antacids (Mg hydroxide, Mg silicate, Al hydrox., Al silicate) may reduce vomiting caused by gastric hyperacidity LAXATIVES AND CATHARTICS They are used for - Relief of acute non-dietary constipation - Removal of poisons from the gastrointestinal tract - Prevention of Tenesmus in advanced pregnancy or prolapse - Evacuation of bowel prior to surgery or radiography LAXATIVES AND CATHARTICS They include - Osmotic cathartics - Irritant cathartics - Bulk laxatives - Lubricants - Surfactants Osmotic cathartics Examples - Mg sulfate (Epsom salt), Mg oxide - Sodium sulfate (Glauber’s salt) - Polyethylene glycol electrolyte solutions - Sodium phosphate and sodium tartrate mixtures (fleet enemas) Irritant cathartics Examples - Castor oil - Aloe - Senna - Cascara sagrada Bulk laxatives Examples - Methylcellulose - Agar - Psyllium - Wheat bran Lubricants and surfactants Lubricants - Mineral oil (liquid petrolatum) and white petrolatum Surfactants – Docusate ANTI DIARHOEAL DRUGS They include - Opiates - Anticholinergic agents - Protectants and adsorbent agents Opiates They include - Paregoric – a camphorated tincture of opium - Diphenoxilate - Loperamide - Codeine Anticholinergic agents They include - Methoscopolamine - Aminopentamide - Propantheline - Isopropamide Protectants and adsorbent agents Preparations - Kaolin-pectin suspensions - Bismuth sub-salicylate DRUGS USED TO TREAT INFLAMMATORY BOWEL DISEASE Examples - Sulfasalazine - Olsalazine - Tylosin - Metronidazole DRUGS FOR TREATMENT OF RUMINANT GASTROINTESTINAL DISORDERS Several groups - Agents for inducing closure of the esophageal groove - Ruminotorics - Rumen antacids - Rumen acidifiers - Viscosity-altering (antibloat) agents Agents for inducing closure of the esophageal groove Example - Milk - Sodium bicarbonate (10% to calves) - Copper sulfate (5% to calves, 2% to lambs) - Ruminotorics They include - Bitters - Cholinergics - Opiate antagonists (eg naloxone) - Rumen fluid transfer Rumen antacids Examples include - Magnesium oxide - Magnesium carbonate - Aluminum hydroxide - Calcium carbonate - Ammonium carbonate Rumen Acidifiers Example - Vinegar - 4%-5% Acetic acid Viscosity-altering (anti-bloat) agents Preparations include - Poloxalene - Polymerized methyl silicone - Mineral oil and - Vegetable oil (e.g. soybean, peanut, sunflower oil).