Lesson 82 - Therapeutic principles of common Intestinal disorders

Protein-losing enteropathy (PLE):

excessive loss of plasma proteins through the GI tract; causes include mucosal inflammation and lymphatic disease

Maldigestion & Malabsorption: general therapeutic principles

Enzyme replacement

Highly digestible diets

Vitamin supplementation

Targeted therapy based on cause

Antibiotics: not a default solution

Chronic Enteropathies (~IBD/IBS): Dietary therapy (first-line in most cases)

Hydrolyzed protein diet

Novel protein elimination diet

Highly digestible diet

Chronic enteropathies: Immunosuppressive therapy

Used when diet alone is insufficient

Common drugs:

Prednisolone (first-line)

Budesonide (selected cases)

Cyclosporine or chlorambucil (refractory cases or cats)

Chronic enteropathies in dogs are often classified according to treatment response rather than a clearly identified cause

Corticosteroids: Anti-inflammatory effects

inhibition of phospholipase A2 → reduced prostaglandins and leukotrienes

decreased cytokine production (IL-1, IL-2, TNF-α)

reduced leukocyte migration and vascular permeability

Corticosteroids: Immunosuppressive effects

suppression of T-cell activation

reduced lymphocyte proliferation

decreased antibody production

apoptosis of some immune cells

In IRE, corticosteroids lead to:

decreased mucosal inflammation

restoration of epithelial barrier

improvement of nutrient absorption

Probiotics: MOA

Microbial competition, Microbiome support

Production of antimicrobial substances

Improvement of intestinal barrier

Immune modulation

Probiotics: Indications

acute canine diarrhea

antibiotic-associated diarrhea

stress-induced diarrhea

some chronic enteropathies

PLE: therapeutic principles

Dietary management: Low-fat diets (especially with lymphangiectasia)

Hydrolyzed or highly digestible diets

Immunosuppressive therapy: For inflammatory or immune-mediated enteropathies

Antithrombotic considerations: Increased risk of thromboembolism in severe PLE

Consider antithrombotic therapy in high-risk patients

Common Causes of short bowel syndrome

Surgical Resection: Removal of part of the small intestine to treat conditions like Crohn's disease, volvulus, necrotizing enterocolitis, trauma, or cancer.

Congenital Defects: An abnormally short, missing, or improperly formed small intestine (intestinal atresia or gastroschisis).

Symptoms of short bowel syndrome

Chronic or severe diarrhea

Greasy, foul-smelling stools (steatorrhea)

Unintended weight loss and malnutrition

Dehydration and low fluid levels

Extreme fatigue, weakness, or lethargy

Cramping, bloating, and gas

SBS: 1. Nutritional management

Highly digestible diet

Low-residue diet

Frequent small meals

Moderate fat (species-dependent)

Supplemental vitamins (especially B12)

SBS: 2. Fluid and electrolyte support

Oral or parenteral fluids

Correction of imbalances

SBS: 3. Control of diarrhea

Antidiarrheals

Fiber

Intestinal dysbiosis and ammonia production: key mechanisms

Microbial Shift: Dysbiosis increases populations of ammonia-producing bacteria(Enterobacteriaceae, Klebsiella, Proteus, Veillonellaceae,Streptococcaceae).

Enzymatic Activity: These bacteria express urease and proteolytic enzymes that convert urea and unabsorbed proteins into ammonia (NH₃) and carbon dioxide.

Colonic pH Changes: Higher ammonia levels elevate colonic pH, which encourages the growth of more pathogenic, acid-sensitive bacteria.

Intestinal dysbiosis and ammonia production: Gut Mucosal Damage

Neurotoxicity (Gut-Liver-Brain Axis): High circulating ammonia crosses the blood-

brain barrier, leading to neuroinflammation, astrocyte swelling, and clinical

manifestations like hepatic encephalopathy (confusion, motor deficits, fatigue).

Excess ammonia is toxic to the intestinal lining, disrupting tight junctions and contributing to "leaky gut" and local mucosal inflammation.

Intestinal dysbiosis and ammonia production: Liver Strain and Hyperammonemia

Gut-derived ammonia travels via the portal vein to the liver, where a healthy liver converts it to urea via the urea cycle.

When liver function is impaired (such as in cirrhosis or fatty liver disease), or portosystemic shunting occurs, systemic blood ammonia levels rise (hyperammonemia).

Intestinal dysbiosis and ammonia production: Neurotoxicity (Gut-Liver-Brain Axis)

High circulating ammonia crosses the blood-brain barrier, leading to neuroinflammation, astrocyte swelling, and clinical manifestations like hepatic encephalopathy (confusion, motor deficits, fatigue).

Intestinal dysbiosis & ammonia production: therapeutic principle

1. Reduce intestinal ammonia production

Feed highly digestible, controlled-protein diets

Use high-quality protein (dairy, egg)

Avoid sudden high-protein meals

Small, frequent feedings

Intestinal dysbiosis & ammonia production: therapeutic principle

2. Modify intestinal microbiota

Lactulose (first-line therapy):

Acidifies colonic contents

Converts NH₃ → NH₄⁺ (non- absorbable)

Promotes ammonia excretion in feces

Antibiotics (if needed): Metronidazole, Amoxicillin

Intestinal dysbiosis & ammonia production: therapeutic principles 3-6

3. Correct precipitating factors(Common triggers: Gastrointestinal bleeding, Constipation, High-protein meals, dehydration, etc)

4. Support hepatic detoxification: IV fluids, correct electrolyte and acid–base disturbances, use hepatoprotective agents

5. Manage neurologic signs: Minimize stress and stimulation… Avoid sedatives metabolized by the liver if possible

6. Treat the underlying cause: Portosystemic shunt… surgery

Chronic hepatopathy: Disease-specific management

Therapeutic principles of bloat(tympany)

Stomach tube - decompression of the GIT

Antifoaming therapy

Correction of diet or underlying disease

Supportive care

Bloat: Antifoaming agents/Oral surfactants

Vegetable oils

Mineral oil

Poloxalene

Simethicone

Bloat: Trocar and Cannula / Surgical Intervention:

Emergency puncturing of the rumen using a trocar or performing a rumenotomy to relieve extreme, life-threatening pressure

Laxatives and constipation medicines

1) Enhancing Excitation (For Underactive Gut/Hypomotility)

Gut moves too slowly, as seen in Gastroparesis or Chronic Constipation; treatments aim to kickstart contractions by boosting excitatory neurotransmitters.

Underactive gut: Acetylcholine (ACh) Amplification and serotonin(5-HT)

ACh is the primary neurotransmitter responsible for muscle contraction in the gut

Serotonin plays a massive role in initiating the peristaltic reflex

Underactive gut: Prokinetics like Pyridostigmine(acetylcholinesterase inhibitor)

prevent the breakdown of ACh, keeping muscles contracting

Underactive gut: Prucalopride or Metoclopramide

5-HT4 receptor agonists stimulate excitatory motor neurons to release more ACh, speeding up transit

Underactive gut: Motilin Receptor Agonists

Motilin is a hormone that triggers the Migrating Motor Complex (the gut's "housekeeping" wave)

underactive gut: Erythromycin

low dose mimics motilin to stimulate strong gastric contractions

Reducing inhibition for underactive gut: Dopamine Antagonists

Dopamine naturally inhibits GI motility by suppressing ACh release.

Domperidone or Metoclopramide block dopamine (D2) receptors → inhibiting the inhibitor, they allow excitatory pathways to take over and increase motility.

3. Enhancing Inhibition / Reducing Excitation (For Overactive Gut / Hypermotility)

When the gut is hyperactive or spasms, as seen in Irritable Bowel Syndrome with Diarrhea (IBS-D) or Esophageal Spasms, the goal reverses

Enhancing Inhibition/Reducing Excitation for Overactive Gut: smooth muscle relaxants

Smooth Muscle Relaxants: Block the calcium channels required for muscle contraction(Dicyclomine, Hyoscyamine, or peppermint oil)

Enhancing inhibition/reducing excitation for overactive gut: opioid receptor agonists

Stimulate mu-opioid receptors in the gut (like Loperamide or Eluxadoline) to reduce the release of excitatory neurotransmitters, effectively slowing down transit and reducing cramping

Neurotransmitters and ENS

Hypomotility (↓ motility)

Hypermotility

Disorders of coordination

Secondary/systemic causes

Types of ileus

Paralytic (functional) ileus – loss of peristalsis due to neural, metabolic, or inflammatory causes

Mechanical ileus – physical blockage of the lumen (foreign body, neoplasia, volvulus, intussusception, hernia)

Prokinetic drugs are

agents that enhance gastrointestinal motility by stimulating excitatory pathways or blocking inhibitory ones

Prokinetic drugs: Parasympathomimetics (e.g., neostigmine, bethanechol)

act as acetylcholine agonists or cholinesterase inhibitors → increase cholinergic stimulation of smooth muscle

Prokinetic drugs: Dopamine antagonists (e.g., metoclopramide, domperidone)

block dopamine’s inhibitory effect → enhance acetylcholine release → improve motility in stomach and proximal small intestine

Prokinetic drugs: Serotonin agonists (e.g., cisapride)

stimulate serotonin receptors in enteric neurons → strong pro-motility effect throughout GI tract

Macrolide Antibiotics(erythromycin most common)

Act as motilin receptor agonists

Administered at low, sub-antimicrobial doses (under MIC)

Stimulate migrating motor complex → improve gastric emptying and intestinal motility

Risk of dysbiosis/antibiotic-associated colitis (Clostridium overgrowth)

Mainly used in small animals for gastric hypomotility, less so in horses

Adjunctive/Local Agents: support motility through regional or indirect mechanisms

Examples and actions:

Lidocaine (IV, horses): reduces sympathetic tone, anti-inflammatory, analgesic → improves post-op ileus

Opioid antagonists (naloxone, methylnaltrexone): counter opioid-induced ileus

Magnesium sulfate/osmotic agents: draw fluid into gut lumen, aiding motility

Therapeutic targets: key receptors

Cholinergic System (↑ Motility): Muscarinic receptors (M2/3)

Adrenergic System (↓ Motility): Adrenergic α2 and β2 receptors

Opioid Receptors (↓ Motility): μ receptors

Serotonin Receptors (~↑ Motility): 5-HT 3/4 receptors

Dopamine Receptors (↓ Motility): D2 receptors

Motilin Receptors (↑ Motility)

Bethanechol: Muscarinic agonist (M3) Effects

Increases the motility of the ileocaecocolonic region in cattle

Increases gastric and cecal emptying

post-operative ileus in horses, gastro-oesophageal reflux in foals

Bethanechol: common adverse effects

Diarrhea

Salivation

Bradycardia

Hypotension

Abdominal cramps

Erythromycin(Motilin-receptor agonist) Effects

Stimulates the pyloric antrum and smooth muscles of the proximal small intestines

postoperative ileus, cecal impactions

Erythromycin adverse effects

Mild abdominal discomfort

diarrhea

Passage of soft feces

Antibiotic-associated colitis

Neostigmine & Ranitidine(AChE inhibitors) Effects

Caecum and colon impactions refractory to other medication

Not first line drugs

Ranitidine is primarily used as histaminic antagonist(increases gastric pH)

Metoclopramide(5-HT-4 receptor agonist, 5-HT-3 antagonist, dopamine antagonist)

Effects

Increases gastric emptying - pigs and sheep

increases esophagus sphincter tone

stimulates duodenum motility: horses

increased rumen motility and functional pyloric stenosis – ruminants

Antiemetic (central effect)

Metoclopramide adverse effects

Restlessness/agitation, Sedation, excitement and collapse

Cross BBB

Domperidone: Dopamine antagonist Effects

Similar to metoclopramide, but does not cross the blood-brain barrier

Domperidone adverse effects

Limited, possible GI upset in dogs and some endocrine effects: increase in prolactin and aldosterone concentrations

Cisapride(Serotonin 5-HT4 agonist) Effects

Increases stomach motility and emptying - dogs, cats

Increases motility of small intestines and colon - horses, dogs, cats, pigs

Cisapride adverse effects

Abdominal discomfort

interference with myocardial potassium influx - cardiac arrhythmias

Spasmolytics: N-butylscopolammonium(Acetylcholine antagonist (M3) Effects

Relaxes smooth muscles in the GI-tract, GI spasms, facilitate rectal palpation in horses

Short duration of action 20-30 minutes, quaternary ammonium compound - no CNS action

Reduced contractility: Loperamide

μ-opioid receptor agonist

Stops diarrhoea

Loperamide adverse effects

Contraindicated in acute infectious diarrhea

No CNS effects because it cannot cross BBB - CNS effects can be observed in dogs with an MDR1 mutation

Species specific reminders: dogs and cats

Dogs: consider parvovirus, foreign bodies, acute haemorrhagic diarrhoea, and chronic enteropathy.

Cats: constipation/megacolon, lymphoma, anorexia-related hepatic lipidosis and species-specific drug safety.

Straining must be distinguished from urinary obstruction in cats.

Avoid sodium phosphate enemas in cats; some dogs with ABCB1/MDR1 variants risk loperamide neurotoxicity

Species specific reminders: Horses and food animals

Equine colic can represent surgical disease; reassess pain and perfusion promptly.

Ruminant neonatal diarrhoea: fluids, electrolytes, glucose, nutrition, passive immunity and hygiene.

Piglet diarrhoea needs herd-level assessment, biosecurity and age-specific differentials.

Food-producing animals: follow approved use, withdrawal periods and local regulations