Transcript Control Mechanisms of the GI Tract

Chapter 11
Gastrointestinal Drugs
Dr. Dipa Brahmbhatt VMD MpH
[email protected]
Basic Anatomy and Physiology
• The term gastrointestinal (GI) tract describes a long,
muscular tube that begins at the mouth and ends at
the anus.
• Structures:
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Oral cavity
Esophagus
Stomach
Small intestine
Large intestine
• Structures vary from monogastric animals with
simple stomachs to ruminant animals with
multichambered forestomachs
– Unobstructed and regulated flow
Basic Anatomy and Physiology
• Accessory Organs: production/secretion of
enzymes that aid in digestion
– Liver
– Gall bladder
– Salivary gland
– Pancreas
Basic Anatomy and Physiology
• Peristalsis
– Contraction of
longitudinal and circular
muscles in gut
– Moves food
– Stretch
receptors
increase
peristalsis
– ANS
• Segmentation
– Periodic, repeated
intestinal constrictions
– Churns GI contents
– ANS
Autonomic Nervous System
Sympathetic = “Fight or Flight”
Parasympathetic = homeostatic
Eat turkey and sleep it off
Control Mechanisms of the GI Tract
• One control mechanism of
the GI tract is the autonomic
nervous system
(parasympathetic and
sympathetic branches)
• Parasympathetic
stimulation
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–
Increases intestinal motility
Increases GI secretions
Relaxes sphincters
Cholinergic drugs simulate
these actions
– Anticholinergic drugs
inhibit these actions (Glyco.
And atropie)
Control Mechanisms of the GI Tract
• Sympathetic
stimulation
– Decreases
intestinal motility
– Decreases GI
secretions
– Inhibits the action
of sphincters
– Sympathetic nerves
simulate these
actions
Control Mechanisms of the GI Tract
• Chemical
• Histamine
• Hormones
– Gall bladder
emptying
H2 Receptor
HCL acid
Gastrointestinal Disorders
• Are the most common complains in vet. medicine
• Underlying causes include:
– Infectious sources
• Gram negative bacterial endotoxin increases b.v. permeability,
increased fluid loss
– Dietary excess
– Adverse drug effects
– Systemic disease
• Liver disease affects bile production and fat digestion
Gastrointestinal Disorders
• These disorders result in clinical signs such as:
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Diarrhea
Constipation
Vomiting
Bloat
Ulcer development
Pain
Drugs Affecting the GI Tract
• Antisialogues
– Drugs that decrease salivary flow
– Used to limit the flow of excess saliva, which often
occurs secondary to anesthetic drug use
• Examples include anticholinergics such as glycopyrrolate
and atropine
– These drugs can also affect peristalsis because they are
also used to treat vomiting, diarrhea, and excess gastric
secretion
• Decreases intestinal motility
• Decreases GI secretions
• Does not relax sphincters
Glycopyrrolate (Robinul) and
Atropine
Use Glycopyrrolate in
Pregnant animals it does not appreciably cross CNS or placenta
Atropine comes in
Two concentration: 0.5 mg/mL (injectable-SA)
and 2.0 mg/mL (injectable-LA)
Diarrhea
– Diarrhea: abnormal frequency and liquidity of fecal
material due to GI tract unable to absorb fluid
– Dehydration and electrolyte imbalance
– Decrease uptake of nutrients
– Muscle weakness
– Acid-base disturbances
– Causes
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Infectious
Foreign body
Toxins
Inflammatory
Neoplasm
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,
thereby allowing fluid absorption from the
intestinal contents
– Examples:
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Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Metronidazole
Coat
inflammed
layer with
protectant
or by binding
Bacteria/
toxin/enz.
Decrease both
intestinal secretion
and flow of feces,
increase segmental
contraction resulted
in increased
intestinal absorption
Blocks acetylcholine release
from parasym. nerve endings
to decrease GI motility and
secretion
Antidiarrheals
Anticholinergics are used to
treat tenesmus (colitis) and
vomiting (colonic
irritation)
– Examples:
• Atropine (InjectableSA)
• Aminopentamide
(Centrine)
• Isopropamide
• Propantheline (ProBanthine) - IBD
• Methscopolamine
(Biosol-M)
• Side effects of
anticholinergics
• Dry mouth
• Constipation
• CNS stimulation
• Tachycardia
• Pupillary dilation
Antidiarrheals - Anticholinergics
Antidiarrheals
• 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/pectin (Kao-forte, kaopectilin)
• Activated charcoal (toxiban, liqui-char)
– Side effects include constipation
Antidiarrheals
• Opiate-related agents
– 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): least CNS depression
• Paregoric: C-III
– Side effects include CNS depression
(excitement:horses & cats), ileus,
urine retention, bloat, and 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
– 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 used to treat
diarrhea
Metronidazole
Passage of
feces is
slowed
or
nonexistent
Laxatives
– Loosens the bowel contents and encourages evacuation of
stool
– Evacuate without excessive straining
– Treat chronic constipation from nondietary causes and
movable intestinal blockages (hair balls)
– Evacuate the GI tract before surgery, radiography, or
diagnostic procedures
– Cathartics are harsher laxatives: soft/watery stool, abd.
cramping
– Purgatives are harsh cathartics
Laxatives
• Types of Laxatives include:
– Osmotic
– Stimulant
– Bulk-forming
– Emollients
Laxatives
• Osmotic
• Pull water into the colon and increase water content in
the feces, thereby increasing bulk and stimulating
peristalsis
• Are salts or saline product that may cause electrolyte
imbalances if absorbed systemically
Enema • Examples include: lactulose, sodium phosphate with
per
sodium biphosphate (Fleet Enema, Gent-L-Tip,
rectum magnesium sulfate (Epsom salts), magnesium hydroxide
(Milk of Magnesia)
• NOT IN CATS, caution in heart and renal failure
Laxatives
• Stimulant
• 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 bisacodyl (Dulcolax): enteric coating,
phenolphthalein, and castor oil (ricinoleic acid)
Laxatives
• Bulk-forming
• Substances that absorb water into the intestine,
increase fecal bulk, and stimulate peristalsis,
resulting in large, soft stool production (which
tends to look normal)
• Are not systemically absorbed, so side effects are
rare
• Examples include psyllium hydrophilic mucilloid,
polycarbophil,and bran
FREE ACCESS TO WATER
Laxatives
• Emollients
• Can be stool softeners (reduce stool surface tension and
reduce water absorption through the colon), lubricants
(facilitate the passage of fecal material, increasing water
retention in stool), or fecal wetting agents (detergentlike drugs that permit easier penetration and mixing of
fats and fluid with the fecal mass)
• Examples include docusate sodium, docusate calcium,
docusate potassium, and petroleum products
Often vomiting can
be controlled by NPO
and correcting
dehydration
Vomiting:
expulsion
of stomach (+/duodenal)
through
mouth
•Sensory: odor/taste
•Ach
Vomiting center: Medulla
in the brain stem
•Neurotransmitter:
Acetylcholine
•Inflammation/ increase in
intracranial pressure
CRTZ
•Indirect Stimulation
•Senses chemical
changes
•Near CNS
•Outside blood-brain
Barrier
•Neurotranmitter
•Dopamine
•Serotonin
•Histamine:
secondary
Stimulate of receptors
semicircular canals in the
inner ear
•Abdominal afferent nerves
•Duodenum
•Vagus n.
Neurotransmitters
Antiemetic Drugs
Cerenia – Maropitant citrate
Metoclopramide - Reglan
Ondansteron (Zofran)
Acepromazine
Benadryl
Atropine
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:
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Phenothiazine derivatives
Antihistamines
Anticholinergics
Procainamide derivatives
Serotonin receptor antagonists
Neurokinin (NK1) Receptor Antagonists
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
• Phenothiazine derivatives (vasodilation,
hypotension)
• Inhibit dopamine in the chemoreceptor trigger zone, thus
decreasing the stimulation to vomit
• Side effects include hypotension and sedation
• Don’t use with epileptics, vomiting animals or
with abnormal GI motility
• Hydration has to be good
• Examples:
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Acepromazine
Chlorpromazine
Prochlorperazine
Perphenazine
Antiemetics
• Antihistamines
• Controls vomiting when the vomiting is due to motion sickness,
vaccine reactions, or inner ear problems
• Work by blocking input from the vestibular system to the CRTZ
• A side effect is sedation
• Examples:
– Trimethobenzamide (Tigan)
– Dimenhydrinate (Dramamine)
– Diphenhydramine (Benadryl)
Antiemetics
• Anticholinergics
• Block acetylcholine peripherally, which decreases
intestinal motility and secretions
• May decrease gastric emptying (which may increase the
tendency to vomit)
• Side effects include dry mouth, constipation, urinary
retention, and tachycardia
• Examples:
– Aminopentamide
– Atropine
– Propantheline
Antiemetics
• Procainamide derivatives
• Work centrally by blocking the CRTZ
(dopamine antagonist) and peripherally
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, (Due to peripheral effects:
gastric motility) or seizures
Antiemetics
• Procainamide derivatives
• An example used in veterinary
medicine is
metoclopramide
(Reglan)
• PO/SQ/IM/IV
• Stimulates motility of upper GI
w/o gastric/biliary/pancreatic
secretions (used with
chemotherapy agents in
humans)
Antiemetics
• Serotonin receptor antagonists
• Work selectively on 5-HT3 receptors, which are located
peripherally (Vagus n.) and centrally (CRTZ)
• Work on the theory that some chemicals
(chemotherapeutic agents/ propofol) cause vomiting
because they increase serotonin release from small
intestinal cells
• $$ and GI upset
• Examples:
– Ondansetron (Zofran)
– Dolasetron (Anzemet)
Extra label in cats
Antiemetics
Oral / SQ
• 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
– Peripheral and central mediated vomiting
• Maropitant citrate (Cerenia®)
– Used to prevent acute vomiting and motion sickness
– Side effects include:
• Pain at the injection site, hypersalivation, pre-travel vomiting
(when given at high doses) and diarrhea
Maropitant (Cerenia®)