Veterinary Pharmacology

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

:Benzodiazepines: Diazepam (Iv) & Oxazepam (Po) -1

GABA stimulation at appetite center , central inhibition of
satiety center
Used in cats ,less effective in dogs
Cyproheptadine: 5HT &Histamine blocker ,used in -2
geriatrics, adults and young people suffering form food
eating
Used in cats, may be not effective in dogs
 Appetizer agents
Glucocorticoides & Vitamin B complex -3
Gluconeogenesis inhibitors: Hydrazine sulfate -4
Gastric empting accelerators :Metoclopramide -5
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, while α2.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 9 th
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)
α2 agonist: fast acting; good to excellent sedation lasts
up to 90-120 min; excellent analgesic activity lasts
15-30 min
α2 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: in emetic center-1
antidopaminregics: in CTZ -2
antihistaminergics: in vestibular apparatus and -3
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 of labrynithitis ,at low doses via anti
dopaminergic and at higher doses by
.antichilonergic mechanisms
Peripheral α 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 Ca2
+

Endocrine pathway: Gastrin by increasing cytosolic

Ca2
+

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 90-
98%
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 pancreatic α 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 cyclo-
oxygenase &lipooxygenase pathways,
interfere with the synthesis of inflammatory
cytokines, inhibit NF.ΚB action, suppress the
activity of NKCs, mucosal lymphocytes
&macrophages
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