Transcript Control Mechanisms of the GI Tract

Chapter 4 - 2
pg 93 - 122
Gastrointestinal Drugs
Dr. Dipa Brahmbhatt VMD MpH, MS
[email protected]
OBJECTIVES
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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
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
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
Antiemetics
• Phenothiazine derivatives (vasodilation, hypotension)
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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:
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Acepromazine
Chlorpromazine: acute gastroenteritis
Prochlorperazine
Perphenazine
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)
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:
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Aminopentamide (Centrine)
Atropine
Isopropamide
Hyoscine (scopolamine: Donnatal human product)
• Useful for irritable bowel syndrome, high **** PNS
Antiemetics
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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) Frenzied cat
– 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
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
Quinuclidine class: Maropitant
(Cerenia®)
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
Diarrhea
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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
Small Intestine
Large Intestine
Amount
Increased
(volume)
Decreased
Frequency
(times/day
2-4
4-10
Tenesmus
No
Yes
Weight loss
+/-
No
Blood
Melena
Frank
Mucous
No
Yes
Antidiarrheals
– Antidiarrheals are drugs that decrease peristalsis
or increase segmental contractions, thereby
allowing fluid absorption from the intestinal
contents
– Examples:
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Anticholinergics
Protectants/adsorbents
Opiate-related agents
Anti-inflammatory drugs
Probiotics
Antibiotics/ antiparasitic drugs: Metronidazole
Antidiarrheals – Modify Intestinal
Motility
Anticholinergics (against Ach)
– used to treat tenesmus (colitis) and
vomiting (colonic irritation)
– Examples:
• Atropine (Injectable-SA)
– Not used often
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– anticholinergic, mydriatic,
cycloplegia
Aminopentamide (Centrine)
Isopropamide
Propantheline (Pro-Banthine) IBD
Methscopolamine (Biosol-M)
– Don’t use in cardiac
arrhythmias, tachycardia (cathyperthyroidism), ileus,
• Side effects of
anticholinergics
• Make SI diarrhea worse
by dec. segmental
contraction and
resistance flow
• Dry mouth
• Constipation
• CNS stimulation
• Tachycardia
• Pupillary dilation
Antidiarrheals - Anticholinergics
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!!!
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
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)
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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)
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Antimicrobial (sulfonamide) and mesalamine (anti-inflammatory)
Ulcerative colitis
Caution in cats
Sulfa SE: vomiting (give with food), dec. tear production
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
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
Probiotics
Lactobacillus spp.
Enterococcus faecium
Bifidobacterium spp.
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
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
References
• Romich, J.A. Pharmacology for Veterinary
Technicians, 2nd edition. 2010.
• Bill, R.L. Clinical Pharmacology and
Therapeutics for the Veterinary Technician, 3rd
edition. 2006.