Vomiting/Diarrhea Pharmacology

Emetics, Antiemetics, Prokinetics, Anti-diarrhea, Cathartics, Laxatives, etc.

Describe the steps of the neural pathway that results in vomiting

1. Stimulus to vomiting center (chemicals, motion, smells, gastric distention, etc.)

2. Emetic center coordinates reflex via CN V, VII, IX, X, and XII

3. Hypersalivation, pallor, sweat, tachycardia

4. Glottis closes (protect airway)

5. Deep inspiration with diaphragm contractions

6. Gastroesophageal sphincter (GES) and fundus relax

7. Abdominal mm. contractions!

8. Antiperistaltic waves

ID which center synthesizes efferent and afferent neural messages to promote vomiting

Emetic center in the medulla receives information (afferent) and sends information (efferent)

Explain the difference between 5-HT₃ and 5-HT₄

5-HT₃: acts centrally

5-HT₄: acts peripherally

What is the effect of a serotonin antagonist bound to 5-HT₄?

Promotes GI motility

MOA of H₂O₂

Peripheral acting agent

Irritates the stomach and thus stimulates CRTZ and CN IX

MOA of ropinerole

Central acting agent

D2 receptors in CRTZ AGONIST

MOA of apomorphine

Central acting agent

D2 receptors in CRTZ AGONIST

MOA of xylazine and dexmedetomidine

Central acting agent

alpha-2 adrenergic receptor AGONISTS in CRTZ

Indications for emetic treatment

• Expel non-corrosive poisons/toxins

• Expel gastric contents if planning general anesthesia induction

How much of the gastric contents are expelled when using emetic therapy?

Only 40-60%

Contra-indications for emetic treatment

• Do not use to expel corrosive material (could cause more damage)

• Do not use during seizures (aspiration risk, lower seizure threshold)

• Not for animals that cannot vomit

• Do not use during any situation that would increase aspiration pneumonia

Indications for anti-emetic treatment

• Confirm that vomiting is disadvantageous

• Ideally: diagnose the cause

Contra-indications for anti-emetic treatment

• GI obstruction: may lead to perforation

• GI toxicity: prevent elimination of toxin

H₂O₂, ropinerole, apomorphine, and xylazine/dexmedetomidine are all examples of which class of drug?

Emetics

Ondansetron, maropitant, and metoclopramide are all examples of which class of drug?

Anti-emetics

Metoclopramide, cisapride, and lidocaine are all examples of which class of drug?

Prokinetics

Which species cannot vomit?

Horses, cattle, rabbits, rodents

What drug is used for treating motion sickness and acute vomiting?

Maropitant (Cerenia)

What drug is used for treating nausea?

Ondansetron

MOA of maropitant (cerenia)

Neurokinin-1 receptor ANTAGONIST

• Binds to NK1 to functionally BLOCK the normal ligand, Substance P

MOA of ondansetron

Serotonergic (5-HT₃) ANTAGONIST

• blocks binding of serotonin to 5-HT₃ receptor

Indications for prokinetic treatment

• Gastric emptying disorders due to chronic inflammatory enteropathy (CIE), pancreatitis, or post-op ileus

What drugs are used as prokinetic treatment?

• Metoclopramide

• Cisapride

• Lidocaine

MOA of metoclopramide

Dopamine antagonist → competes with dopamine for D2 receptor within peripheral and central components

• Promotes progressive motility from the esophagus to the proximal small intestine

Which GI drug works at both the peripheral and central level? How does it work in each level?

Metoclopramide

Central @ CRTZ

• Dopamine receptor antagonist + 5-HT₃ receptor antagonist = block vomiting reflex

Peripheral @ GI tract

• 5-HT₄ agonist + sensitizes muscarinic receptors = promote gastric motility and emptying

MOA of cisapride

Serotonin agonist → bind to 5-HT₄ to mimic endogenous seretonin

• Indirect stimulation of cholinergic nerves (ACTh related) which increases intestinal contractions

MOA of lidocaine

• Suppresses afferent neural pathways from the peritoneum

• Induces analgesia and anti-inflammatory properties

• Directly stimulates smooth muscle

What drugs can be used for diarrhea care?

• opioids

• bismuth subsalicylate

• kaolin/pectin

• probiotics

What drugs are ruminotorics?

• Poloxalene

• Mineral oil and water

Outline the principles of treating diarrhea

• Treat underlying cause

• Replace/maintain fluid/electrolyte balance

• Dietary rest with slow return to feeding

• GI tract rest with antimotility agents

MOA of opioids in treating diarrhea

Anti-motility → slow intestinal transit and reduce secretion while stimulating absorption

• Act at peripheral opioid receptors in the GI tract

  • Increase anal sphincter tone

  • Disrupt normal peristalsis

  • Rude secretory activity

What opioid is commonly used in treating diarrhea?

Loperamide (imodium)

MOA of bismuth subsalicylate (pepto bismol)

Protectant

• Adsorbs toxins

• NSAID (don’t use in P with ulcer hx)

• ± Antisecretory and antimicrobial effects

MOA of kaolin/pectin (kaopectate)

Protectant

• Adsorb bacteria and coat inflamed mucosa

MOA of probiotics

• Alter intestinal microflora

• May decrease adherence of pathogenic bacteria

• May decrease mucosal permeability and inflammation

What are the risks of cathartic/laxative overuse?

Overuse can lead to severe dehydration, colic, and shock

Difference between cathartics and laxatives

Cathartics → accelerate defecation

Laxatives → ease defecation by promoting soft-formed stool

What drug class are lactulose and magnesium sulfate?

Cathartics: osmotic agents

What drug class does castor oil fall under? MOA?

Cathartics: irritant agents

• Stimulates water secretion in SI → prompt evacuation of the whole intestinal tract, leading to almost complete emptying

List the drugs that fall under (1) laxatives, (2) surfactants, and (3) bulking agents

Laxatives

• Petrolatum (Kat-A-Lax)

• Mineral oil

Surfactants

• Dioctyl sodium sulfosuccinate (DSS)

Bulking agents

• Psyllium hydrophilic mucilloid (metamucil)

• Dietary fibers

MOA of petrolatum (kat-a-lax)

Laxatives

• Lubricates hairballs in GI tract

• Impairs water reabsorption for softer stools

Indications to use mineral oil

Impaction colic in horses via NG tube

MOA of dioctyl sodium sulfosuccinate (DSS)

Surfactant

• Stimulates mucosal cell H₂O secretion

• Decreases surface tension in lumen to promote H₂O retention

You should NOT administer dioctyl sodium sulfosuccinate (DSS) with which medication?

Mineral oil → will cause soap formation

What medication should you not administer if abdominal surgery is imminent and why?

Dioctyl sodium sulfosuccinate (DSS) → serosal lining of the gut exposed to DSS will get extremely inflamed

MOA of psyllium hydrophilic mucilloid (metamucil)

Bulking agent

• Increase bulk of intestinal content by absorbing water → promote reflex motility

List two examples of dietary fibers that act as bulking agents

Bran or prunes

Which agents can break down frothy bloat? List 2 examples.

Ruminotorics → promote motility and decrease incidence of frothy bloat

• Poloxalene

  • Antifoaming agent that reduces surface tension

• Mineral oil + water