1. Chapter 4 - 2 pg 93 - 122 Gastrointestinal Drugs
Dr. Dipa Brahmbhatt VMD MpH, MS

2. OBJECTIVES Basic physiology that controls the GI tract
Mechanism of emesis and antiemetics
GI motility and drugs that affect these
Mechanism of GI ulcers and anti-ulcer drugs
Drugs modification in the ruminant GI tract

3. Antiemetics Vomiting has many causes including:
Viral and bacterial infections, dietary indiscretion, food intolerance, surgery, pain, GI disease, kidney/liver failure, metabolic conditions (hypoadrenocorticism), CNS disorders or other drugs
The vomiting center of the brain have many inputs that tell it to activate including:
Equilibrium changes in the ear, responses due to pain or fear, intracranial pressure changes, vagus nerve stimulation in the GI tract, and activity in the chemoreceptor trigger zone

4. Antiemetics Antiemetics
Drugs that control vomiting that help alleviate discomfort and help control electrolyte balance
Most are given parenterally, as the patient may vomit the medication before it can be absorbed through the GI tract
Examples:
Phenothiazine derivatives: Acepromazine, Chlorpromazine, Prochlorperazine (Compazine)
Antihistamines: Dimenhydrinate (Dramamine), Diphenhydramine (Benadryl)
Anticholinergics
Procainamide derivatives
Serotonin receptor antagonists

5. Antiemetics Phenothiazine derivatives (vasodilation, hypotension)
Alpha adnergic receptor antagonist (hence vasodilates)
Vomiting by motion sickness
Block dopamine receptors in CRTZ and emetic center
Antihistamine effects helps with motion sickness in dogs
Does not stop PNS (GI, peritoneal, pharyngeal or other *visceral) effectively unless in high doses
Side effects include hypotension and sedation
Don’t use with seizure animals (exacerbates condition),
vomiting animals or with abnormal GI motility
Hydration has to be good
Examples:
Acepromazine
Chlorpromazine: acute gastroenteritis
Prochlorperazine
Perphenazine

6. Antiemetics Antihistamines
Block H1 receptors in the CRTZ from vestibular system
Large # H1 receptor – CRTZ - dog
Controls vomiting when the vomiting is due to motion sickness, vaccine reactions, or inner ear problems
Not effective for PNS or * Vagus n.
gastroenteritis
A side effect is sedation
Don’t use 4 days before allergy testing
Examples:
Trimethobenzamide (Tigan)
Dimenhydrinate (Dramamine)
Diphenhydramine (Benadryl)

7. Antiemetics
Anticholinergics (Sympathomimetic/ parasympatholytic nervous system drugs)
Block PNS (vagus n.) - acetylcholine peripherally, which decreases intestinal motility and secretions
May decrease gastric emptying – gastric atony (which may increase the tendency to vomit)
Side effects include dry mouth, constipation, urinary retention, and tachycardia
Examples:
Aminopentamide (Centrine)
Atropine
Isopropamide
Hyoscine (scopolamine: Donnatal human product)
Useful for irritable bowel syndrome, high **** PNS

8. Antiemetics Prokinetics: Cisapride (Propulsid)
Procainamide derivatives or Prokinetics
Work centrally by blocking the CRTZ (dopamine (more in dogs hence better for them) and serotonin receptors)
Peripherally (prokinetic) by speeding gastric emptying, strengthening cardiac sphincter tone, and increasing the force of gastric contractions
Should not be used in animals with GI obstructions, GI perforation, or GI hemorrhage
SE: sedation (don’t use with phenothazine tranquilizers)
An example used in veterinary medicine is metoclopramide (reglan)
Chemotherapeutic agents
Bile (duodenum) and mucus vomitus in otherwise healthy
Dog
Prokinetics: Cisapride (Propulsid)
Serotonin antagonist effects
Cats – megacolon
Off market: human arrhythmias but available
for vets in compounding pharmacies
Frenzied cat

9. Antiemetics Serotonin receptor antagonists
Work selectively on 5-HT3 receptors, which are located peripherally and centrally - CRTZ
Work on the theory that some chemicals cause vomiting because they increase serotonin release from small intestinal cells
Examples:
Ondansetron (Zofran): 0.5 – 0.1 mg/kg
Chemotherapy, parvovirus $$
Dolasetron

10. Quinuclidine class: Maropitant (Cerenia®)

11. Antiemetics Neurokinin receptor antagonists
Work on NK1 receptors located in the center of the brain
Work by inhibiting substance P, the key neurotransmitter involved in vomiting
Maropitant citrate (Cerenia®)
Used to prevent acute vomiting and motion sickness
Side effects include:
Pain at the injection site, hypersalivation, and diarrhea
Extra label in cats

12. Diarrhea
Diarrhea: abnormal frequency and liquidity of fecal material due to GI tract unable to absorb fluid
Exudative diarrhea: protein/ fluid/ serum or blood loss in lumen
Dehydration and electrolyte imbalance
Decrease uptake of nutrients
Muscle weakness
Acid-base disturbances
Causes
Infectious: bacterial endotoxins,
parvovirus, transmissible
Gastroenteritis - swine
Foreign body
Toxins: toxins
Inflammatory
Neoplasm
Metabolic: EPI – young shepherds
Laxatives

13. Small Intestine
Large Intestine
Amount
Increased (volume)
Decreased
Frequency (times/day
2-4
4-10
Tenesmus No
Yes
Weight loss
+/-
Blood
Melena
Frank
Mucous

14. Antidiarrheals
Antidiarrheals are drugs that decrease peristalsis or increase segmental contractions, thereby allowing fluid absorption from the intestinal contents
Examples:
Anticholinergics
Protectants/adsorbents
Opiate-related agents
Anti-inflammatory drugs
Probiotics
Antibiotics/ antiparasitic drugs: Metronidazole

15. Antidiarrheals – Modify Intestinal Motility
Side effects of anticholinergics
Make SI diarrhea worse by dec. segmental contraction and resistance flow
Dry mouth
Constipation
CNS stimulation
Tachycardia
Pupillary dilation
Anticholinergics (against Ach)
used to treat tenesmus (colitis) and vomiting (colonic irritation)
Examples:
Atropine (Injectable-SA)
Not used often
anticholinergic, mydriatic, cycloplegia
Aminopentamide (Centrine)
Isopropamide
Propantheline (Pro-Banthine) - IBD
Methscopolamine (Biosol-M)
Don’t use in cardiac arrhythmias, tachycardia (cat-hyperthyroidism), ileus,

16. Antidiarrheals - Anticholinergics

17. Antidiarrheal – Modify Intestinal Motility
Opiate-related agents (scheduled drugs)
Narcotic analgesics control diarrhea by decreasing both intestinal secretions and the flow of feces and increasing segmental contractions
Examples:
Diphenoxylate (Lomotil, lonox, diphenatol). C-V
Loperamide (Imodium: OTC): least CNS depression
Paregoric (tincture of opium): C-III, older drug
Side effects include CNS depression
(excitement:horses & cats), ileus,
urine retention, bloat, constipation and may increase contact time between pathogen and gut!!!

18. Antidiarrheal - Block Hypersecretion
Secretions from
Enterotoxins
Leukotrienes PG
Increase affect of Ach or PNS
Pulls electrolytes and can cause severe dehydration esp. young
Can become exudative diarrhea if GI lumen is compromised >> protein loss, rbc, sugar, fluid

19. Antidiarrheal - Block Hypersecretion
Anti-inflammatory drugs
Salicylates (aspirin like compounds)
Salicylate: antisecretory by blocking PG
Bismuth in bowel: tarry stool looks like melena
Bismuth subsalicylate (bismuth + aspirin-like
product)
DON’T USE IN CATS (no more than 24 hrs)
Not specific
Pepto bismol, corrective mixture (w/opium): refrigerate to increase palatability
Kaopectate: breaks in gut to bismuth carbonate (coating agent) and salicylate
Flunixine Meglumine (Banamine, flunixamine)
Mostly for colic horses
Calf scours
Not canine/feline: ulcers
Sulfasalazine (Azulfidine): sulfonamide + salicylate (mesalamine)
Antimicrobial (sulfonamide) and mesalamine (anti-inflammatory)
Ulcerative colitis
Caution in cats
Sulfa SE: vomiting (give with food), dec. tear production

20. Antidiarrheal - Adsorbents and Protectants
Protectants & Adsorbents
Protectants coat inflamed intestinal mucosa with a protective layer
Adsorbents bind bacteria and/or digestive enzymes and/or toxins to protect intestinal mucosa from damaging effects
Examples:
Bismuth subsalicylate (bismuth + aspirin-like
product)
DON’T USE IN CATS
Not specific
Pepto bismol, corrective mixture (w/opium)
Kaolin (adsorb)/pectin (Kao-forte, kaopectilin)
Dec. absorption of some antibiotics and digoxin
New kaopectate: 130mg aspirin and 230 mg
(extra strength) >> 1Tbsp >> toxicity 5 lb cat
Activated charcoal (toxiban, liqui-char)
Side effects include constipation

21. Antidiarrheals Probiotics
Probiotics seed the GI tract with beneficial bacteria; use is based on the theory that some forms of diarrhea are caused by disruption of the normal bacterial flora of the GI tract
Must be refrigerated to maintain the viability of the bacteria
Examples:
Plain yogurt with active cultures
Variety of trade-name products

22. Probiotics Lactobacillus spp. Enterococcus faecium
Bifidobacterium spp.

23. Antidiarrheals Metronidazole (Falgyl)
A theory regarding the development of diarrhea is that anaerobic bacteria may increase due to disruption of normal GI flora
One way to treat this is to use an antibiotic effective against anaerobic bacteria
Metronidazole is an example of an antibiotic and antiparasitic used to treat diarrhea

24. Metronidazole Tablets, suspension
Bitter tasting (cats hate this, foam in the back of mouth), if smash up and put in food, they will stop eating
Narrow margin toxicity: CNS problems, ataxia

25. References
Romich, J.A. Pharmacology for Veterinary Technicians, 2nd edition
Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3rd edition