Veterinary Pharmacology

Pharmacology GIT Dr. Jahangir Kaboutari Assistant Professor of Pharmacology Faulty of Veterinary Medicine, University of

Importance and function of the GIT Physiology of the GIT Pathology of the GIT, primary and secondary disease Correct DX and specific and non specific treatments

Nonspecific treatment regimens Correction of water and electrolyte imbalance GIT rest Modulation of food regimen and nutrition supply Amelioration of visceral pains

Appetizer agents Appetite center :ventrolat nuclei of the hypothalamus Regulators :Neurotransmitters and neuropeptides Stimulatory NTs:Nep(α2.R), Dopamine(D1.R),GABA Inhibitory NTs: 5HT Stimulatory NPs: Opioids, Pancreatic polypeptides Inhibitory NPs:Calcitonin, Cholecystokinin , Corticotrpin releasing factor

Appetizer agents :usually nonspecific

Appetizer agents -1 Benzodiazepines::(Diazepam (Iv) & Oxazepam (Po GABA stimulation at appetite center , central inhibition of satiety center Used in cats ,less effective in dogs Cyproheptadine: -2 5HT &Histamine blocker ,used in geriatrics, adults and young people suffering form food eating Used in cats, may be not effective in dogs

Appetizer agents -3Glucocorticoides & Vitamin B complex -4 Gluconeogenesis inhibitors:Hydrazine sulfate

Gastric empting accelerators : -5Metoclopramide Megetrol acetate -6 Anti chycotic ,antidepressant drugs -7 Bitters -8 Zinc -9

Emetic & antiemetic agents Protective reflex mechanism , didn’t developed in all spp:Carnivorous, primates, swine, reptiles , some birds: capable of vomiting Horse ,ruminants, rodents, guinea pig and rabbit : incapable of vomiting Multicentral control

Emetic center Lat. reticular formation of the medulla, protected by BBB An integrating center for all emetic impulses Cerebral cortex:pschycologic, visual& olfactory emesis Limbic system: emesis due to head injury & increase in ICP

Ach is the primary NT, Histamine via H1 is the secondary NT

(Chemoreceptor trigger zone (CTZ Area postrema in the lat .wall of the 3rd ventricle Incomplete BBB, nerve endings in direct contact with CSF, therefore more susceptible than emetic center to the blood& CSF born agents , toxins and disease conditions : uremia , pyometra, liver disease,

endotoxemia, radiation sickness disease, apomorphine, estrogens, digitalis, narcotic analgesics Dopamine is the main NT, whileα2.R in dog & cats,H1.R and 5HT.R may be involved as the secondary NTs

Vestibular apparatus Impulses originates form semicircular canal vestibular nucleus via 8th cervical nerves via CTZ and cerebellum to emetic enter Emesis due to motion sickness and labrynithitis H1.R is the main NT, afferent emetic impulses transmitted via Vague nerve Peripheral emetic impulses due to stimulation or distention of the visceral organs transmitted via 9th cervical nerve, Ach is the main NT

The aim of induction of emesis is to emptying the frontal portion of the GIT before induction of anesthesia and in the case of non corrosive, non irritant toxin ingestion Emetic agents:1- centrally acting peripherally acting -2

Peripherally acting emetic agents Distention of the hallow organs by warm water & hydrogen peroxide Oral administration of warm saturated salt solution, placement a block of sodium carbonate in the pharyngeal area of dog Oral administration of 3% hydrogen peroxide solution to dog & cat Oral administration of Ipecac syrup

Ipecac syrup OTC, contains Emetine alkaloid , used in pediatric medicine Peripheral action by gastric irritation, central action by CTZ stimulation Side effects: salivation ,lacrimation ,bronchial secretion & diarrhea and lethargy in human Overdose :potentially cardio toxic, hypotension ,arrhythmia and fatal myocarditis Max administration volume :15 ml While repeated administration cause no emesis gastric lavage should be done Don’t use with activated charcoal due to reduced activity

Centrally acting emetic agents Apomorphine synthetic morphine derivative with little sedative effects Dopaminergic R stimulation in CTZ Fast acting:5-10 min after SC or conjunctival .adm CTZ stimulation while emetic center suppression:less emetic effect in repeated administration Emetic of choice in dog:SC or intraconjuctival CNS stimulation> CNS depression

Contraindications:CNS or respiratory depression; ingestion of strong acid, base & petroleum products; hypoxia and dyspenia ; shock; in the absence of normal laryngeal reflexes; coma, seizure; severe physical weakness; apomorphine sensitivity; CNS depressant toxicity and in unconscious patients

Over dose symptoms:CNS depression; restlessness; respiratory depression; protracted emesis, in these cases administration of narcotic antagonist ( e.g. Naloxone 0.04mg/kg ) is useful

Phenothiaze derivatives interact and negate emetic effect of apomorphine

Centrally acting emetic agents (xylazine (Rumpon α 2 agonist:fast acting; good to excellent sedation lasts up to 90-120 min; excellent analgesic activity lasts 15-30 min

α 2 stimulation in CTZ:fast acting(1-5 min after IM administration) emetic in cat

0.05mg/kg: emesis without sedation Contraindications: cardiac arrhythmia ; Epi administration especially in the case of Halothane anesthesia , during 3rd trimester of pregnancy

Other CNS depressant agent exacerbate its sedation Antagonist :Yohimbine (cat:0.5mg/kg,Iv; dog: (0.1mg/kg ,Iv

Used as a short acting analgesic agent in horse colic Ruminants are so sensitive to Xylazine sedation, .used cautiously especially in small ruminants sedation time lasts more in ruminant than in horse

Antiemetic agents Severe and prolong emesis leads to water and electrolytes excretion; acid-base imbalance and metabolic acidosis Antiemetic agents: 1-centarlly acting peripherally acting -2

Centrally acting antiemetics Block the emetic impulses at higher cerebral centers muscarinic anticholinergics:-1 in emetic center antidopaminregics: -2in CTZ antihistaminergics: -3in vestibular apparatus and secondarily in CTZ& emetic center

Centrally acting antiemetics vestibular apparatus Antihistamines:Cyclizine. HCl ;Meclizine. HCl;

Diphenhydramine. HCl

Control motion sickness and emesis due to labrynithitis No effect on emesis form other origins Side effects:Drowsiness & xerostomia Duration of action: 8-12 h

Centrally acting antiemetics antimuscarinics Belladonna alkaloids: (Hyoscine (scolpolmaine synthetic agents :Dicyclomine.HCl; Isopropamide iodide

Control motion sickness in dog Side effects:Drowsiness & xerostomia Duration of action: up to 6 h Due to potential side effects contraindicated in cat

Centrally acting antiemetics CTZ acting agents Phenothizine derivatives -1 butyrophenone derivatives -2 metoclopramide -3 Trimethobenzamide.HCl -4 5HT antagonists -5

CTZ acting agents Phenothiazine derivatives Chlorpromazine;Prochloperazine;Triflupromazine; Perphenazine;Trifluoperazine,Meprazine Broad spectrum antiemetic in small animals Affect almost all centrally origin emesis except those oflabrynithitis ,at low doses via anti dopaminergic and at higher doses by .antichilonergic mechanisms Peripheralα blockade:sedation& hypotension and .may be need to fluid replacement therapy

CTZ acting agents Butyrophenone derivatives (Haloperidol (Haldol); Droperidol(Inaspine Antidopaminergic; potent antiemetic& sedative Antipsychotic agents in human Side effects like phenothiazines

CTZ acting agents (Metoclopramnide (Reglan 5HT antagonist &Antidopaminergic sensitivity of the upper GIT smooth muscle to Ach: stimulates upper GIT movement and accelerates gastric emptying No effect on gastric, pancreatic& billiary secretions Broad spectrum agent :control emesis due to blood born agents and peripheral stimuli

times more potent than phenothiazines in 20 control of apomorophine induced emesis Increases lower esophageal sphincter tone : uses in the treatment of esophageal reflux & gastric motility disorders in human; abomasal impaction and emptying in sheep and cattle, intestinal ileus in horse

Good oral absorption; crosses placenta and enters milk,T1/2=90 min in dog Contra indications:GIT hemorrhage, obstruction and perforation; seizure

Side effects motion restlessness in dog; disorientation and frenzy like behaviors in cat and constipation Iv injection in adult horse:severe CNS effects; alternating periods of CNS stimulation &depression,behavuoral changes , colic ( less (common in foals Extra pyramidal effects, temporary hypotension& elevated prolactin level in human and may be in animals may affect Insulin dose and timing

Drug interactions Atropine &narcotic analgesics negate GIT effects Absorption of drugs which mainly absorb in the small intestine:Cimetidine,Aspirin,Diazepam Tetracycline, Acetaminophen

Absorption of drugs which mainly absorb in the stomach:Digoxin Modification of dose or timing of Insulin injection Phenothiazines;Butyrophenoines;sedative&narcotics: exacerbate extra pyramidal effects

CTZ acting agents Trimethobenzamide.HCl((Tigan Potent antidopaminergic, weak antihistaminergic Just suppresses CTZ ,no effect on emetic center Controls emesis due to:radiation sickness disease, drugs, infections, anesthesia and uremia

CTZ acting agents 5HT antagonists Ondansetron (Zofran):5HT3.R blockader ;especially effective in cases of Cispaltin and other cancer chemotherapeutics induced emesis

Cyproheptadine: antiemetic in dog & cat To control Psychological –behavioral emesis: sedatives such as barbiturates& diazepam can be used

Peripherally acting antiemetics Untiulcer drugs& those that prevent GIT epithelium form further irritation Anticholinegics &prokinetics which accelerate GIT motility

Glycopyrrolate,Propantheline,methoscopolamine ,Isoproopamide: inhibition of afferent vagus nerve impulses , ameliorate spasm of the GIT smooth muscles, inhibition of entro-gastric secretions, don’t cross BBB ,delays gastric emptying and should not be used more than 3 days Methoscopolmine :contraindicated in cat

Antiulcer drugs Acid secretion :gastric ,cephalic& intestinal phases food induced acid secretion , basal phase spontaneous secretion

H+-K+( ATPase in parietal (oxyntic cells Neurocrine pathway: Ach & muscarinic R, increase cytosolic Ca+2

Endocrine pathway: Gastrin by increasing cytosolic Ca+2

Paracrine pathway: Autaciodes& Histamine H2R, cAMP and cAMP dependent protein kinase

Mocusal defense mechanisms Bicarbonate secretion into the GIT lumen Thick layer of alkaline mucus Gastric epithelial barrier High mucosal blood flow Rapid reipthelialization Production of cytoprotective agents Gastric acid secretion is the prerequisite for gastric ulcer formation

Anti ulcer drugs :Antisecretory agents -1 1-1anticholinergics H2 blockers 1-2 proton pump inhibitors 1-3 PGE1 analogs 1-4

Cytoprotective agents -2 antacids 2-1 PGE1 analogs 2-2 sucralfate 2-3

Antisecretory agents : anticholinergics Hyoscine (scolpolamine) ,Dicyclomine.HCl; Isopropamide iodide Decrease food induced acid secretion up to30% Potentiate the effects of H2 blockers Pirenzepine and selective M1 subtype blockers inhibit up to 60% of food induced acid secretion with fewer side effects

Antisecretory agents :H2 blockers Cimetidine (Tagamet), Famotidine(Pepcid),Nizatidne(Axid), (Ranitidine(Zantac

Competitive and reversible H2 blockers which decrease acid and pepsin secretion Potency:Ranitidine 5-12>Cimetidine, Famotidine 9>Ranitidine while 32> Cimetidine

Famotidine: longest duration of action

Cimetidine Rapid oral absorption, food delays absorption Hepatic enzyme inhibitor, decreases HBF therefore decreases metabolism of: Phenytoin,Theophyline,Digitoxin,Diazepam, Lidocaine,Morphine

By increasing gastric PH increases concentration of:Tetracycline,Erythromycin& Penicillin G ,while decreases concentration of Ketoconazle

Antacids may delay its oral absorption therefore they should be administered at least 1hours before or after Cimetidine

:Indications Treatment or prevention of gastric, duodenal & abomasal ulcers; uremia induced gastritis; esophigitis; stress or drug induced erosive gastritis; .duodenal gastric reflux Acid hyper secretion due to gastrinoma and systemic .mastocytosis Gastric bleeding of the upper portions of the GIT .which is not due to damage of large vessels Exocrine pancreatic insufficiency:30 minutes before .meal .Prevention of GIT side effects of corticosteroids In uermic dogs decreases Parathyroid secretion, bone resoption ,phosphate serum level Gastric ulcers in horse

Contraindications: sensitivity to drug, in pediatrics

and those patients with severe hepatic& renal .insufficiency Side effects: dizziness, headache , antiandrogenic effects which leads to gynecomastia , azospermia & decrease libido, skin rashes,, diarrhea and constipation, agranulocytosis (rare in human), transient cardiac arrhythmia and bradycardia (rapid Iv .(injection

Relapse of gasrtoduodenal ulcers, may be due to rebound hyper secretion Famotidine& Nizatidine :less likelihood of rebound hyper secretion while Cimetidine has the most potential for rebound hyper secretion

Ranitidine :less bioavailability than Cimetidine, elimination T1/2=2/5 h , Oral absorption doesn't .affected by the presence of food

Famotidine: little oral absorption, unchanged urine .excretion

Nizatidine: rapid & complete oral absorption ,unchanged urine excretion, H2 blocker of choice in .renal insuffiency cases

Antisecretory agents :Proton pump inhibitors

Omeprazole(Prilosec) ,Esmoprazole(Neium),Lansoprazole(Prevacid),Panto (prazole(Protonix),Rabeprazole(Aciphex Potent H+-K+ATPase proton pump inhibitors Omprazole :30>antacid potency than Cimetidine Weak base, acid labile ,inactive entric coated capsule or slow release formulation, absorption takes place in intestine

Selective protonation in parietal cells, concentrates up to 1000times and activates, irreversible proton pump .inhibition Lag time =3-5 days Inhibits basal and food induced acid secretion up to 9098% Food decreases bioavailability up to 50%,should be administered 1 hour before meal Inhibits cytochrome P.450 hepatic enzymes :decreases metabolism of :Diazepam,Phenytoin,warfarin Increases gastric PH and decreases absorption of drugs that need low PH for absorption :Ketoconazole, ester and metal salts of Ampicillin

:Indications Drug of choice :Zollinger –Ellison syndrome Treatment of gastro duodenal ulcers A paste form is available for treatment & preventions of relapse of gastric ulcer in horse Pain amelioration in gastric ulcers Acid secretion control in cases not responding to H2 blockers Gastro esophageal Reflux Disease (GERD), Gastric ulcers related to NSAIDs& H. pylori, Prevention of stress related mucosal bleeding Gasrtinoma and other conditions leading to acid hyper secretion

Side effects Well tolerated in human, dog and cat GIT disturbances:anorexia, colic, nausea& emesis, bloat, diarrhea GIT infections, protenurea, CNS disturbances (Hematological abnormalities( rare in human Decrease in absorption and serum level of Vit.B12 Duration of treatment:dog 4weeks,hore up to 90days,in human more than 8 weeks is rare

PG E series (Misoprostol (cytotec Interaction with basolat.mem receptors of parietal cells, decreases cAMP production and cAMP .dependent protein kinase activity Orally active, local action Decreases basal, nocturnal and food induced acid secretion No rebound acid secretion Less effective than H2 blockers in decreasing luminal PH & pain relief duo to peptic ulcers

Indications Primary or adjunctive drug in treatment or prevention of case of peptic ulcers related to NSAIDs Relief of symptoms of atony Decrease or reversal of cyclosporine induced nephrotoxicity Due to stimulation of amplitude& frequency of uterine contractions, uterine bleeding,uterine content expulsion, softness& opening of cervix can be used as a adjunctive drug in termination of pregnancy

of an oral dose absorbed rapidly 88% Fist pass effect ,hepatic metabolism with an active metabolite, urine excretion Food &antacids delay drug absorption without effects on clinical efficacy Causations in use:sensitivity to PG or PG analogs,

coronary vessel diseases, cerebral diseases Side effects:transient GIT disturbances including diarrhea, abdominal pain, bloat emesis, uterine bleeding and contraction in female dogs Mg containing antacids may exacerbate emesis related to Misoprostol

Cytoprotective agents: Antacids Alkalinizing agents which bind to and inactivate gastric acid& Pepsin Bind to bile acids,stimulte mucosal protectants such as PGE series & sulfhydrils increasing gastric PH up to 3-4 without induction of systemic alkalosis Antacid capacity: water solubility, rate of reaction with acid, rate of gastric emptying, rate of dissolution of tables forms

Antacid may interfere with oral absorption of: Oral iron preparations, Digoxin, Corticosteroids, Captopril, Ketoconazole, Nitrofurantoin, Penicillamine, Phenytoin, Ranitidine, Cimetidine, Tetracycline

Concurrent administration may increase serum level of :Aspirin, Quinidine, sympathomimetic agents

Indications : Gastric hyperacidity, peptic ulcers, gastritis, reflux esophagitis, chronic renal failure, prevention of rumen acidosis related to grain overload

Antacids: Sodium bicarbonate Systemic, rapid& short acting antacid, water soluble solution is isotonic 1.5% May cause metabolic alkalosis especially when used in high dose or in renal insufficiency Produced NaCl may causes water retention in cardiac &renal insufficiency, hypertension cases

:Indications Treatment of metabolic acidosis Urine alkalization Adjunctive therapy : hypercalcemic,hyperkalemic crisis's Treatment of metabolic acidosis related to neonatal diarrhea& rumen lactic acidosis

:Contraindications Metabolic or respiratory alkalosis Sever Chloride loss secondarily due to emesis or suction of gastric content, risk of hypochloremic alkalosis related to diuretics Hypocalcemia because of the risk of tetany

:Drug compatibility PH, cencentration,temperature& type of diluent Incompatible with:,5%alcohol,5%dextrose,injectableVit C Codeine, Epinephrine, Glycopyrrolate ,Hydromorphone ,regular Insulin , Isoproterenol, Labetalol , Imipenem , Levorphanol , Mg. sulfate , Meperidine ,Methadone , Oxytetracycline , Tetracycline , Procaine , Secobarbital , Streptomycine ,Succinyl choline Mix with Ca2+ containing fluids:insoluble complexes Oral drugs :administer 2 hours before or after sodium bicarbonate

Antacids:aluminium hydroxide Al.phosphate, Al. magnesium silicate No systemic antacid, good absorbent&protectant by local stimulation of protective PGs Increase gastric ph up to 4 ,rebound acid secretion doesn't takes place Insoluble Al.phosphate complex formation leads to decrease phosphate absorption& control the serum .phosphate in renal diseases Constipative:used with Mg salts to minimize constipation & increases antacid capacity May be protective if administered with drugs such as NSAIDs& Aminophylline which are not well tolerated in patients

Contraindicated in alkalosis Use with causation in gastric outlet obstruction due to delay in gastric emptying May deplete phosphate, causes muscular weakness, bone resoption and hypocalcaemia ,(Rapid onset of action (less than 30 minutes Due to short duration of action should be administered ever 3-4 hours

Antacids: magnesium containing products Mg hydroxide ( milk of magnesia), Mg oxide, Mg silicate Increase gastric PH up to 9 and induce rebound acid secretion Laxative nature Rapid and long lasting antacid effect Normally up to 20% of Mg can be absorbed systematically, which increase in renal failure and in repeated administration which may leads to hyper magnesia

Antacids: Calcium carbonate Potent, rapid acting, long lasting antacid Side effects:metabolic alkalosis, rebound hyper secretion ,hypercalcemia ,calciuria , metastatic calcification , urolithiasis and constipation may develop slowly

Cytoproptectives:PGE1 (Misoprotol(Cytotec Increases mucus ,bicarbonate secretion& mucosal blood flow ,enhances reeipthelialization Stabilizes mast cell membrane damaged by ulcerogenic agents Treatment & prevention of peptic ulcer related to NSAIDs Not effective as H2blockers in the inhibition of gastric acid secretion but is superior in enhancing

gastro duodenal healing

Cytoprotectives: sucralfate ((Carafate .An alkalinizing Al.hydroxide complex with sucrose .Local effects>systemic effects Reacts with gastric HCl, forms a insoluble pasty complex , bind to exudates protein of the damaged tissue (anions of the GIT epithelium cell membrane) which forms a barrier in the

damaged area and protects the damaged tissue .form more injuries by acid, bile and pepsin .Bind with and inactivates bile acids & pepsin

Binds with &accumulates epidermal growth factor .in damaged area Stimulates local production of PGI2,PGE2 & nitric oxide which leads to increase in mucosal blood .flow .Directly stimulates mucosal angiogenesis Some antacid activity, may decrease gastric emptying rate Least systemic absorption after oral adm and least . side effects Max protection depends on gastric acidity( PH<5) .for activation The safest drug for treatment of gastro duodenal .ulcer

prokinetics Enhance transit of GIT content by inhibition of inhibitory transmitters e.g. Dopamine or promotion of excitatory transmitters e.g. Ach Species and organ specificity cholinergic agents -1 metoclopramide -2 domperidone -3 cisaparide -4

Prokinetics: cholinergic agents Bethanechol Choline ester selectively binds M2 receptors with GIT and urinary activity Increases peristalsis and tone of lower esophageal sphincter, gastric and intestinal peristaltic activity , gastric and pancreatic secretions, tone of detrusor muscle Over dose :increases bronchial contraction &secretion,miosis,salivation and lacrimation

:Indications Large animals: stimulation of gastrointestinal activity, post operative gastrointestinal ileus, stimulation of urination, enhancement of gastric emptying and minimizing gasrtoesophageal reflux in foals Feline dysautonomia for promotion of urination :Contraindications Obstruction of urinary outlets, hyperthyroidism, peptic ulcer or inflammatory condition of the GIT, recent surgery of the GIT with anatomists/resection, GIT obstruction, seizure, asthma, hypotension, sever bradycardia, co administration with other cholinergic agents

:Drug interactions Procainamide, epinephrine, sympathomimetic amines, atropine negate its effects Ganglion blockers intensify GIT effects & hypotension Side effects Mild in small animals:vomiting , diarrhea, salivation &anorexia

Horse : (salivation,lacrimation& colic( potentially Overdose:asthma, cardiac arrhythmia & hypotension Antidote: Atropine

Prokinetics: metoclopramide Peripheral effects:increases Ach release from intrinsic nerves, inhibition of D2 receptors which leading to increases force and frequency of gastric contractions in antrum portion ,relaxation of pyloric sphincter , enhancement of peristaltic motility in the duodenum& jejunum, promotes gastric emptying

Prokinetic indications:treamnet of gastric motility disorders e.g. gastric distension, post operative paralysis, peptic ulcers, idiopathic gasrtoparesis, gastric torsion

Prokinetics: Domperidone D2 blocker, don’t cross BBB as readily as metoclopramide Peripherally coordinates antroduodenal contractions and enhances transit time,no effect on colon motility Anti emetic & prokinetic agent in small animal:more effects on conditions due to delay in gastric emptying than gastric hyper motility Uses cautiously in Collie dogs Don’t use with dopaminergic agents Antacids & H2 blockers decrease absorption of drug

Prokinetics: Cisapride Broadest spectrum oral prokinetic agent Dose dependent Indirectly increases Ach release form myenteric nerves, no interaction with dopamine receptors and no extra pyramidal effects Prokinetic effects:esophagus, stomach, small intestine& colon

Good oral absorption with first pass effect

Indication in small animals:esophageal reflux,

treatment of primary gastric stasis disorders, constipation& mega colon Contraindications :obstruction, perforation & bleeding of the GIT

May have anticoagulant effects Intensifies sedative effects of alcohol& benzodiazepines Don’t administer with :Ketoconazole,

Itaconazole&Tetracycline due to risk of ventricular arrhythmia

Protectant & Absorbents No oral absorption, used commonly in anti diarrhea agents Protectants:make a lining layer to protect GIT epithelium form further irritation by noxious agents

Absorbents: bind physically with chemicals and hinder their absorption

Mg. trisilicate, Kaolin, Pectin, bismuth salts , Ca2+ carbonate, activated charcoal , Al. trisilicate, Al.hydroxide, Al. phosphate

Kaolin -Pectin Absorbent& demulcent ,line the GIT epithelium, improve feces consistency Kaolin is a potent coagulant agent, can be useful in treatment of diarrhea related to mucosal erosion and bleeding Can cause constipation especially in dehydrated patients

Bismuth salts Bismuth sub salicylate, bismuth sub nitrate, bismuth sub carbonate Bismuth sub salicylate: absorbent, anti endotoxin,weak antibacterial Hydrolyzed to Bismuth carbonate& salicylate,while most effect are related to bismuth, salicylate plays role as anti PG to control secretory diarrhea Main indication :control of diarrhea By making a protective lining layer & formation of insoluble complexes with noxious agents can be useful in improving mal indigestion

Useful in the treatment of flatulence and its bad smell Drug of choice in the treatment of acute diarrhea Contraindicated in salicylate hypersensitivity Fecal discoloration Radiopaque and may interferes with GIT radiography Interferes with oral absorption of other drugs e.g. Tetracycline Chronic use:encephalopathy& osteodytrophy Cats are so sensitive specially in conditions of intestinal inflammation

Activated charcoal , The broadest spectrum ,rapid acting absorbent useful in the emergency treatment of intoxications Forms stable complexes with noxious agents& enhances their excretion Administration every 6 h for 1-2 days increases elimination of systemic absorbed toxins Usually administer with a laxative or emetic agent with gastric lavage Optimal ratio to toxin:10 to 1used in 6 hours Food decreases efficiency

Best results in toxicity with:Acetaminophen, Atropine, cardiac glycosides, phenytoin, strychnine, morphine& ethylene glycol

Not effective in toxicity with:cyanides, mineral acids, basic corrosive agents, organic solvents, ethanol, lead, iron & methanol

Ipecac syrup negates absorbent effect Indication :absorption of intestinal gasses in bloat, gastric dilation ,indigestion

Cholestyramine resin Basic anion exchange resin Non specific absorbent, decreases absorption of bile acids, lipoproteins, cholesterol& neutral acids Indication:symptomatic treatment of diarrhea, specific treatment of pruritus related to increase in bile acids Side effects:nausea , constipation, decrease in absorption of the fat soluble vitamins, steatorrhea

Should be administered with food or water

Laxatives &cathartics Enhance deification by increasing volume or frequency of fecal mass Laxatives make soft feces, while cathartics make watery feces and are more potent than laxatives Emollient laxatives -1 Simple bulk laxatives-2 Irritant cathartics-3 Osmotic cathartics -4 Neuromuscular cathartics-5

Emollient laxatives Mechanical or lubricant laxatives No gastric absorption just soften and lubricate fecal mass Mineral oils e.g. liquid paraffin are mild & safe Anionic surfactants e.g. dioctyl sodium sulfosuccinate or docusate. Na+, dioctyl calcium sulfosuccinate :stool softener

Liquid oils: liquid paraffin Long term use:interference with absorption of the fat soluble vitamins, nutrients and coadministered drugs, decrease sensitivity &irritability of intestinal mucosa which can leads to constipation, intestinal and lymphoid absorption which lead to granulomatous injuries

Mal administration :lipid pneumonitis Not suitable for diagnosis or treatment of GIT obstruction

Simple bulk laxatives Methyl cellulose , carboxy methyl cellulose ,Psyllium seeds ,wheat bran Hygroscopic agents not absorbed in GIT , remain in GIT , absorb water and swell,producuing a bulky emollient gel which distend GIT& increase peristaltic motility and lead to watery feces Cellulose & hemi cellulose undergo bacterial fermentation in large intestine, make volatile FA which precipitate laxative effect by osmotic character Metorism & excess watery feces may be result

Osmotic cathartics Salts which not absorbed from GIT, remain and absorb water by osmotic pressure Onset of action:3-12 hours in simple stomach,after18 hours in ruminants

Water free access ,contraindicated in dehydrated patients Mg salts e.g. Mg. sulfate; Mg .hydroxide (Epsom salt) ;Mg. oxide; Mg. citrate; Na+ .sulfate; Na+ phosphate; potassium sodium tartrate; sugar alcohols e.g. manitol, sorbitol & disaccharide lactolose

Mg salts: release CCK Mg. sulfate containing compounds often not use in horses Sugar alcohols :bacterial breakdown to produce organic acids e.g. lactic acid which decrease colon PH ,absorb water by osmotic effects& enhance colon motility

Lactolose:treatment of chronic constipation &hepatic encephalopathy

Irritant cathartics Stimulate lining mucosa of the GIT, initiate local myneteric reflexes which leads to enhancement of intestinal transit Plat oils e.g. castor oil, olive oil, linseed oil; diphenyl methanes .e.g. Bisacodyl; Anthraquinones e.g. Danthrone Lipase hydrolysis in small intestine, release fatty acid , form Na+ & K + salts ,produce irritant soaps Direct or indirect acting Contraindications : intestinal obstruction, non diagnosed rectal hemorrhage, suspection to intestinal obstruction

Castor oil Rapid acting Should be followed by bulky, wet meals Use primarily in nonruminants ,often in cattle s& foals Duration of action: 4-8 hours in small animals,12-18 hours in large animals

Bisacodyl Inhibits glucose absorption& Na+-K+ATPase, direct stimulation of sensory nerve ending in colon wall, increases epithelial permeability & fluid content of colon lumen Oral or rectal cathartic in dog &cat Onset of action:6-10 hours after oral administration ,15 minutes after enema

Indication:decease constipation and cleaning colon for colonoscopy, after dehydration it is useful for treatment of sever impaction of the GI Side effects: sometimes cramp & diarrhea

Anthraquinones: Danthrone Emodin cathartics, often with plant origin Indirect acting in large intestine :bacterial

hydrolysis , release active aglycans ( Emodin) which stimulate myenteric plexus of the large intestine

Avoid of repeated administration in large animal duo to slow onset of action May change the color of urine Senna& casgara sagrada: natural antraquinone glycosides

Neuromuscular purgatives Neostigmine; Physostigmine; bethanechol;carbachol Muscarinic cholinergic agents act at small intestine, fast acting:10-30 minutes after parentral administration,2-4 hours after oral administration

May exacerbate colic, use cautiously in physical obstruction Neostigmine: less side effects, used for the treatment of

ruminal atony, enhance urination, stimulation of skeletal muscles contraction& peristaltic activity in cows, horses, sheep's& swine's; treatment of curare like drug intoxication in dogs, and invermectine intoxication in cats

Glucocorticoides decrease the efficacy of drug

Generally laxative &cathartics are used for the enhancement& precipitation of GIT motility ,emptying the GIT, treatment of constipation & GIT impaction Side effects:severe and protracted diarrhea,

abdominal colic which can leads to dehydration & even shock, decrease n the irritability of the intestinal mucosa , mega colon, bloat, loss of electrolytes, secondary aldosteronism, steatorrhea, protein losing gastroentropathy, severe calcium loss & osteomalsia& exacerbation of inflammatory intestinal diseases

Enema Placement of or administration of liquids or suppositories in the rectum to initiates defecation .reflex, a simple way for treatment of constipation Enemas e.g. water soap, isotonic or hypertonic NaCl solution , sorbitol, glycerol, sodium lauryl .sulfoacetate, mineral oils, love oil Phosphate containing agents should not be used in cats, debilitated & weak animals because of the risk of fetal hyper phospahtemia,hypocalcemia& hypernatremia without correct diagnosis

digestants Digestive agents used therapeutically for enhancement of digestion to treat some diseases of the GIT and include natural digestive enzyme and or related compounds Pepsin plus HCl:used in gastric achylia or absence of HCl or digestive enzymes in gastric juice Diastases:amylolytic enzymes used for as the replacement therapy of pancreaticα amylase and also control of bloat

Pancreatic extracts:used as replacement therapy in the cases of exocrine pancreatic insufficiency due to ,chronic pancreatitis,pancreatic hypoplasia

powder or non coated crushable tablets Bile acid& salts e.g. dehydrocholic acid; chenodeoxycholic acid enhance absorption of long chain fatty acids& fat soluble vitamins ,stimulates bile secretion form hapatocytes

Antidiarrhea agents Diarrhea usually accompanies with increase in digestive motility, decrease in transit time, increase in water and electrolyte excretion (Na+; Cl-; K+; H+) which can leads to metabolic acidosis Acute diarrhea may responds to symptomatic therapy whit anti diarrhea agents, while chronic ones need to correct diagnosis

Antidiarrhea agents:1. opiates Diphenoxylate; Lomotil ;Paregoric; Loperamide Inhibition of Ach release, decrease the peristaltic motility and constriction of gastric lumen, increase the tone of gastric sphincters ,increase in transits time & absorption of water and electrolytes Opiates are generally used for the symptomatic treatment of acute diarrhea

Diphenoxylate Synthetic congener of Meperidine Decreases abdominal pain& colic Duration of treatment:36-48 hours Side effects:constipation, bloat & sedation May stimulate CNS in cats Should not be used in the case of intestinal inflammations Exacerbates the effects of :barbiturates; phenothiazines; anti histamines& anesthetic agents

Lomotil: diphenoxylate combined with atropine

Antidiarrhea agents: Loperamide Used for treatment of diarrhea in dogs, acute colitis& mal indigestion/mal absorption Side effects:sedation, constipation& ileus, may stimulates CNS in cats Contraindications:severe bacterial enteritis, hepatic diseases, obstruction of the GIT& urinary tract, &glaucoma Collie dogs are more sensitive If after 48 hours symptoms of diarrhea don’t improve ,drug administration should be discontinue

Antidiarrhea agents: Paregoric tincture of opium Used for the treatment of diarrhea in cats, horses &cattle's once a day

Antidiarrhea agents:2. anticholinergics Aminopentamide; propantheline; Isopropamide; methscopolamine Aminopentamide used for the treatment of acute abdominal spasm, tenesmus, pylorospams, hyperthropic gastritis and related emesis, emesis & diarrhea in dogs and cats Contraindications:sensitivity to anticholinergic agents, obstruction of the GIT, ulcerative colitis& bacterial infections

Antidiarrhea agents:3.protectants& absorbents Kaolin –pectin suspension; Kaolin –pectin suspension

Absorb toxins and make protective layer which prevent gastric mucosa from further injuries Used for the symptomatic treatments of acute diarrhea Kaolin –pectin suspension used every 4-6 hours orally in dog, cat, horse cattle& sheep; bismuth sub salicylate used orally in horse and cattle every 6-8 hours

Drug used in intestinal inflammation Aminosalycilates (Drugs contain 5.amino salicylic acid (5ASA Rapid absorption to the upper portions of the small intestine, often act locally at the inflamed intestinal mucosal area Azo compounds& Mesalamine compounds: formulation for releasing 5ASA to the different parts of small intestine or colon

Modulate inflammatory mediators via cyclooxygenase &lipooxygenase pathways, interfere with the synthesis of inflammatory cytokines, inhibit NF.ΚB action, suppress the activity of NKCs, mucosal lymphocytes ¯ophages 5ASA:1st line drug for the treatment of mild to moderate cases of ulcerative colitis

5ASA compounds:useful for the treatment of mild to moderate cases of crohn,s disease that involved distal ileum &colon

Azo compounds of 5ASA Sulfasalazine:5ASA plus s.pyridine Balsalazide:5ASA plus 4- amino benzoyl-β- alanine Osalazine:a combination of 2 molecule of 5ASA Azo combination decreases the absorption of 5ASA form small intestine ,in the terminal portion of ileum & colon 5ASA detached and can reach to ileum & colon S.salazine :many side effects due to the systemic absorption of s.pyridine especially in slow acetylators

Mesilamine compounds Pentasa: contain micro granules to releases 5ASA throughout the small intestine Asacol: covered with PH sensitive resin, releases 5ASA in the distal ileum and frontal portion of colon Rowasa & Canasa:formulated to release 5ASA in the sigmoid colon& rectum

Glucocorticoids Prednisolone; prednisone;hydrocortisone;budenozoide Generally used for the treatment of moderate to severe inflammatory intestinal diseases For the treatment of inflammatory conditions involve rectum or sigmoid colon rectal administration is the route of choice

Tylosin Macrolide antibiotic which binds to 30s ribosome subunit, inhibits protein synthesis and thus it is bacteriostatic Used orally for the treatment of chronic colitis in small animals ,2-3 times per day with food

Metronidazole A bactericidal antibiotic by disruption of DNA Affect almost obligatory anaerobic bacteria e.g. Clostridium. Spp; Fusobacterium; Peptococcus; Peptostreptococcus

Affect protozoa's with Trichomonacidal& amoebocidal activity, also affect Balantidium coli,Giardia& Entamoeba histolytica Inhibits cell mediated immune reactions

Indications :treatment of giardiasis, trichimonasis, balantidium coli, colic, systemic & digestive infections related to susceptible anaerobic bacteria's( small animals); infection related to anaerobic (bacteria's (horses

Contra indications: sensitivity to nitroimidazole derivatives, debilitated patients, pregnant animals ,milking mothers &human food producing animals

Caution : coadminstration with warfarin & other cumarin anticoagulants due to increase in prothrobnim time

Ruminotoric agents Potentiate rumen contractions Neostigmine &bethanechol :increase the frequency of ruminal contraction transiently, used Sc in the cases of ruminal atony

Opioid antagonists e.g. Naloxone: potentiate ruminal contractions, used for the treatment of endotoxin related rumen stasis

Bitters e.g. red pepper, ginger& noxvomica: stimulate rumen contractions by stimulation of salivation

Rumen anta acids Mg.oxide; Mg.carbonate; Al.hydroxide; Al.carbonate; Ca .carbonate Used for the treatment of rumen lactic acidosis related to grain overload Administration:orally every 8-12 hours Overdose especially Mg.oxide:risk of systemic alkalosis

Rumen acidifiers Vinegar& acid acetic 4-5% Indication:simple indigestion, treatment of acute urea toxicity by inhibition of urease enzyme and formation of non absorbable ammonium ion which decrease ammonia absorption

Mixed with cold water and administrated via gastric tube every 6-8 hours

Anti bloat agents Bloat :aggregation of gas in the GIT due to inability to expel of gas

Frothy bloat : increase in the surface tension of rumen content and trapping of gas bubbles Anti bloat agents: compounds which decrees surface tension of rumen contents e.g. Poloxalene; paraffin ; plans oil such as; soybean oil, sunflower oil, almond oil

Dioctyl sodium sulfosuccinate:used for the treatment of frothy bloat in ruminants, abdominal impaction & mega colon in horse( max dose in (hose:200mg/kg

Poloxalene: used for the prevention of bloat in ruminants

Dimethicone: decrease the surface tension and used for the treatment of bloat and other GIT disorders with gass aggregation