Transcript Control Mechanisms of the GI Tract

Chapter 4 - 3
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
Passage of
feces is
slowed
or
nonexistent
LAXATIVES – CATHARTICS PURGATIVES
• Increase fluid content in feces
• Uses
– Chronic constipation
• Older cats
– Trichobezars
– Evacuate colon
• Radiographs
• Pelvic fractures
• Perianal Sx.
• Most gentle to harsh
– Laxatives (soften) < Cathartics (evacuate) <
Purgatives (evacuate)
LAXATIVES – CATHARTICS PURGATIVES
• Types of Laxatives
include:
– Emollients
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Mineral oil
Cod liver oil
White petrolatum
Glycerin
Docusate sodium
succinate (Colace)
– Bulk-forming
• Types of Cathartics
include:
– Osmotic
• Hypertonic salts
– Milk of magnesia
– Epsom salts
• Lactulose
– Stimulant/ Irritant
• Castor oil
Laxatives
• Emollients
• Examples include
– Mineral oil
» Horse – impactions given orally.
» NB: aspiration pneumonia
» Dissolve lipid soluble toxins
– Cod liver oil and white petrolatum
» Cats and dogs
» Dissolve lipid soluble toxins (for toxins???)
» NB: chronic use decrease absorption of
lipid soluble vitamins (ADEK)
– Glycerin
» Suppository
» Pelvic fractures,
– Docusate sodium succinate (Colace), docusate calcium, docusate potassium
» Change surface tension of feces > water can penetrate – wetting agent
» Anal surgery: anal sacculectomy, perianal fistula surgery
Laxatives
• Bulk-forming laxatives
• Substances that pull water into the intestine or
retain water, increase fecal bulk, and stimulate
peristalsis, resulting in large, soft stool production
(which tends to look normal)
• Not systemically absorbed: side effects are rare
• Hydrophilic colloids (indigestible fiber)
– Psyllium (flatulence)
– Methylcellulose
– Bran
FREE ACCESS TO WATER
Cathartics
• Osmotic
• More potent than osmotic bulk laxatives
• Poorly absorbed
• Hypertonic salts: that may cause electrolyte imbalances if absorbed
systemically, dehydration if large doses
• Release cholecystokinin: hormone that increases peristalsis and
of fecal material
Enema • movement
E.g.: include: lactulose, sodium phosphate with sodium
biphosphate (Fleet Enema), Gent-L-Tip, magnesium sulfate
per
(Epsom salts), magnesium hydroxide (Milk of Magnesia)
rectum • Lactulose: Ionizes ammonia hence less absorbed. It is used in
chronic constipation (reduce ammonia absorbed) hepatic
encephalopathy
• Phosphate salts: hypocalcemia > tetany
• Mg salt: excess > muscle weakness and CNS alterations
– NOT IN CATS
• Use with caution in heart and renal failure
Cathartics
• Stimulant/ Irritant
• Increase peristalsis by chemically irritating sensory
nerve endings in the intestinal mucosa
• Many are absorbed systemically and cause a variety of
side effects
• Examples include castor oil (ricinoleic acid), bisacodyl
(Dulcolax): enteric coating and phenolphthalein
– Castor oil > duodenum > ricinoleic acid: irritant
• Caution: don’t use in obstructed bowel or impacted
feces, tenesmus
Physiology of stomach acid
• Stomach is lined:
Gastric glands – proximal stomach:
– Oxyntic/ parietal cells (lumen) – HCL acid
– Chief cells – pepsinogen in low pH
> pepsin: digest proteins
– Goblet cells (Mucous cells) – protective mucus –
mucins and bicarbonate ion also secreted > neutralizes
and protects stomach cells
• Distal stomach: G cells – hormone: gastrin >
*gastric glands > parietal cell > HCL acid
• Gastritis > Gastric ulcers/ erosions: Breaks
in mucus, epithelium and underlying
mucosa
• Caused by failure to secrete mucus
• H + ions in stomach : energy expenditure
• Parietal cell – blood side: receptors for
*gastrin, *Ach, *histamine > optimum HCL
• INCREASED HCL: Stomach stretched > Ach>
gastrin (G cells – antrum) > relax fundus
Causes:
• hyperacidity,
• reflux bile – duodenum,
• accumulation of metabolic toxins – renal
failure
• Stress: surgery, disease
• Inhibits PgE
• Carb overload ruminants
• Drugs: NSAID: aspirin, phenylbutazone,
flunixin meglumine (Banamine)
ANTACIDS AND ANTIULCER
DRUGS
• Nonsystemic antacids
– Mg products: Riopan,
Mylanta
– Aluminum products:
Amphogel
– Mg and Al: Maalox
– Ca products: Tums and
rolaids
• Systemic antacids
– H2 blockers
• Cimetidine (Tagamet)
• Famotidine (Pepcid)
• Ranitidine (Zantac)
– Misoprostol (Cytotec)
– Omeparazole
– Sucralfate (Carafate)
Antiulcer Drugs
• Antiulcer drugs
– Decrease stomach acidity
– Categories include
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Antacids
Histamine-2 receptor antagonists
Mucosal protective drugs
Prostaglandin analogs
Proton pump inhibitors
Antacids
• Decrease stomach acidity (increase stomach pH
• Nonsystemic: PO
» Magnesium hydroxide (Riopan and Mylanta)
» Aluminum hydroxide (Amphojel): cats CRF
» Aluminum/magnesium hydroxide (Maalox): balanced
» Calcium carbonate (Tums and Rolaids)
» SE: chronic use electrolyte imbalance
» Ca
• Ca and Al: SE constipation
• Can have gastric acid rebound trigger release of
gastrin
• Don’t give with tetracycline antibiotics
» Mg: diarrhea
» Reduce absorption of digoxin, acepromazine,
corticosteroids: Don’t give 2 hours before or 3 hours
after giving these drugs
Antiulcer Drugs
• Systemic
• Histamine-2 receptor antagonists/ H2 blockers
• Prevent acid reflux by competitively blocking the H2 receptors of
the parietal cells in the stomach, thus reducing gastric acid secretion
• Examples:
– Cimetidine (Tagament®)
– Ranitidine (Zantac®)
– Famotidine (Pepcid®)
• Cimetidine and ranitidine: inhibit hepatic enzymes
breakdown of: beta blockers, ca channel blockers, quinidine,
diazepam, phenytoin
Antiulcer Drugs
• Proton pump inhibitors
• PO
– Less than 40 lbs. powered drug from capsule to smaller gelatinn capsule or
freeze with margarine
• Bind irreversibly to the H+-K+-ATPase enzyme on the surface of
parietal cells of the stomach; this inhibits hydrogen ion transport
into the stomach so that it cannot secrete HCl
• Examples:
– Omeprazole
– Lansoprazole
Antiulcer Drugs

Mucosal protective drugs: “Band Aid”
 Combine with protein to form an adherent substance that covers
the ulcer and protects it from stomach acid and pepsin
 Stimulate PgE release
 An example is sucralfate
Antiulcer Drugs
• Prostaglandin analogs
• Suppress gastric secretions and increase mucus
production in the GI tract
• An example is misoprostol, (Cytotec: PgE1)
• Better as treatment for NSAID toxicity than
prevention
• SE: diarrhea, abdominal discomfort, cramping,
colic
• Expensive
Ruminatorics
– Stimulate atonic or flaccid rumen
– Older: Mercury, strychnine, tartar, barium chloride, plant
concoctions
– Neostigmine
• Combines with acetylcholinesterase and > breakdown on Ach
• *PNS > inc. *GI, inc. bronchial secretions, bronchoconstriction,
bradycardia, miosis, urination
Bloat: ruminal tympany
– Free gas (mineral oil) or frothy bloat
– Home remedies: oil of turpentine, pine oil, gasoline,
creolin, formaldehyde
– Used in ruminants, whose rumens are subject to acute
frothy bloat
– Make this foam less stable, breaking it up to promote gas
release through belching
– Examples include poloxalene, Dioctyl sodium succinate
(DSS)
• Oral or inject into rumen (early stages)
Motility Enhancing
• Prokinetic agents
– Increase the motility of parts of the GI tract to enhance
movement of material through it
– Types of prokinetic agents are:
• parasympathomimetics
• dopaminergic antagonists
• serotonergic agents
Prokinetic Agents
• Dopaminergic agents stimulate
gastroesophageal sphincter, stomach, and
intestinal motility by sensitizing tissues to the
action of the neurotransmitter ACh
• Examples include metoclopramide and domeridone
• Serotonergic agents stimulate motility of the
gastroesophageal sphincter, stomach, small
intestine, and colon
• An example is cisapride
Enzyme Supplements
– Pancreatic enzymes must be supplemented in the diet
when the pancreas is not functioning properly (as in
pancreatic exocrine insufficiency)
– Pancreas lipase contains primarily lipase, but also
contains amylase and protease
– Can be irritating to the skin on contact and to nasal
passages upon inhalation
Antimicrobials
• Metronidazole: Giardia
– SE: CNS: head tilt, staggering, disorientation,
proprioceptive deficits and seizures
• Tylosin (Tylan)
– Macrolide
– Bovine and swine: gram + and gram -: Chylamydia
and Mycoplasma infections
– DON’T USE IN EQUINE severe DIARRHEA
Appetite-Stimulating Drugs
• Serotonin antagonist antihistamines
– Promote appetite by inhibition at the serotoninergic receptors
which control satiety
– Side effects include sedation and dry mouth
• Benzodiazepines
– Effective appetite stimulants in cats but not dogs
– Side effects include sedation and ataxia
• Tetracyclic antidepressants
– Stimulate appetite by antagonizing alpha2-receptors
– Side effects include sedation, vocalization
Appetite Stimulating Drugs
• Glucocorticoids
– Stimulate steroid-induced euphoria which stimulates
appetite
– Side effects include polydipsia, polyuria, dull haircoat,
weight gain, and behavioral changes
• Anabolic steroids
– Stimulate hematopoiesis, appetite, and weight gain
– Side effects include hepatotoxicity, masculinization, and
early closure of growth plate in young animals
Appetite Stimulating Drugs
• Progestins
– Used to stimulate appetite and promote weight gain in
anorectic cats and dogs
– Side effects include behavioral changes, endometritis, and
mammary enlargement
Appetite Suppression
• Dirlotapide (Slentrol®)
– Drug for management of obesity in dogs
– Side effects include vomiting, diarrhea, lethargy, and
anorexia
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.
• http://www.vivo.colostate.edu/hbooks/pathphy
s/digestion/stomach/anatomy.html