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CE Article 1
Vomiting
❯❯ H
éctor J. Encarnación, DVM
Gulf Coast Veterinary
Specialists
Houston, Texas
❯❯ J oshua Parra, DVM
Florida Veterinary Referral
Center and 24-Hour
Emergency and Critical Care
Hospital
Estero, Florida
❯❯ E rick Mears, DVM, DACVIM
Valerie Sadler, DVM, DACVR
Florida Veterinary Specialists
and Cancer Treatment Center
Tampa, Florida
At a Glance
The Vomiting Reflex
Page 122
Antiemetics
Page 124
Vomiting Reflex
Components, Receptors,
and Controlling
Neurotransmitters
and Medications
Page 125
Most Common Antiemetics
Used in Small Animal
Medicine
Page 127
Treatment of Common
Vomiting Conditions
Page 128
Most Common Causes of
Vomiting in Dogs and Cats
Page 129
122
Abstract: Vomiting is the forceful expulsion of stomach contents through the mouth, caused by
humoral stimulation of the chemoreceptor trigger zone (CRTZ) or neural stimulation of the emetic
center. The CRTZ is activated and controlled by neurotransmitter manipulation at the receptor
level. Clinical signs preceding vomiting may include ptyalism, tachycardia, depression, hiding,
and yawning. Gastritis, gastrointestinal ulceration, pancreatitis, motion sickness, uremia, chemotherapy, and drug administration are common initiating causes of vomiting. This article reviews
the anatomic and physiologic aspects of the vomiting reflex and its neurotransmitters, associated
receptors, and rational management.
E
mesis, or vomiting, is one of the
most common reasons dogs and
cats present for medical evaluation.1 Vomiting is often associated with
mild, self-limiting diseases that resolve
with minimal diagnostic tests and therapy.
However, it can be related to debilitating
conditions that have life-threatening consequences. The history obtained from the
client should be as detailed as possible
because historical details are often helpful
in selecting the appropriate treatment and
diagnostic plan. Questions to ask during
the history should include onset of vomiting, duration of clinical signs, type and
frequency of vomiting, relation to food
ingestion, characteristics of the vomited
contents, diet history, and environment.
Questions about known medical conditions and current therapies are also pertinent because these factors may play an
active role in the inciting cause.
The Vomiting Reflex
Pathophysiology
Vomiting is a reflex act that is mediated
neurologically by the activation of the
bilateral nucleus tractus solitarii, or emetic
center, situated in the parvicellular reticular formation in the lateral region of the
medulla oblongata. This is the area that
initiates, controls, regulates, and organizes the vomiting reflex.2–5
Vomiting can be triggered by both
neural and humoral pathways.2 The neural pathway comprises six fundamental
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components. The emetic center (1)2,6–12
receives input from (2) the gastrointestinal
tract (afferent neurons),2,7–11,13 (3) the higher
centers of the brain,2,7–9,13 (4) the vestibular apparatus,2,6–13 and (5) the CRTZ.2,6–13
Finally, to coordinate the vomiting reflex,
the vomiting center sends signals through
(6) the efferent motor neurons.7,8,10 The
vagal and sympathetic afferent neurons
originate from the gastrointestinal tract,
particularly the duodenum, as well as
other areas, including the urinary and
reproductive system, liver, pancreas, peritoneum, and cardiac vessels. Stimulation
of these neurons initiates the impulse that
travels directly to the emetic center. The
higher centers of the brain, including the
cerebral cortex and the limbic system, can
trigger emesis through three mechanisms:
direct stimulation of the vomiting center by
inflammatory diseases, hydrocephalus, or
neoplasia; psychogenic stimulation caused
by fear, stress, excitement, or pain; and traumatic stimulation related to head injuries
and increased intracranial pressure.7,9
The CRTZ is a bilateral set of centers in
the brainstem, located on the floor of the
fourth ventricle. It possesses free nerve endings that maintain direct contact with the
cerebrospinal fluid via ependymal pores or
the sheath surrounding fenestrated capillaries.9,14 These free nerve endings are activated by the vestibular system or through
the humoral pathway by conditions affecting the blood or cerebrospinal fluid (e.g.,
drug administration, infection, osmolar
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CE Vomiting
and acid–base disorders, electrolyte
derangements, metabolic diseases).15
Finally, to initiate the vomiting
reflex, efferent motor signals must
be transmitted to the upper gastrointestinal tract through the sensory
aspect of cranial nerves V, VII, IX,
X, and XII and to the diaphragm
and abdominal muscles via the spinal nerves.8
Anatomy
negative intrathoracic pressure and
positive intraabdominal pressure,
facilitating the movement of gastric
contents into the esophagus. Before
expulsion, the respiratory center is
inhibited and the nasopharynx and
glottis close to prevent pulmonary
aspiration and nasal regurgitation of
the gastric contents. The third and
last phase of vomiting is the expulsion of stomach contents through the
mouth.
The act of vomiting is composed of
three phases: nausea, retching, and Antiemetics
expulsion of proximal duodenal Antiemetics are drugs that block the
and gastric contents.6,7,16 Nausea is vomiting reflex 9,23,24 by impeding
the conscious recognition of sub- neurotransmission at central (CRTZ,
conscious excitation in an area of emetic center) and peripheral (gasthe medulla that is closely associ- trointestinal
epithelium)
recepated with the vomiting center. This tor sites. These drugs are classified
excitation is caused by irritative based on the type of receptor they
impulses coming from the gastroin- block (Table 1). However, antiemettestinal tract, lower brain, or cerebral ics have the potential to prolong gascortex.15,17–19 Ptyalism, tachycardia, trointestinal infections, predispose
nervousness, hiding or seeking patients to such infections, and preattention, shivering, and yawning vent toxin elimination by decreasare all characteristic signs of nau- ing gastrointestinal motility. The use
sea triggered by general activation of most of these drugs in animals
of the sympathetic and parasympa- is off-label, and some dosages are
thetic branches of the autonomic extrapolated from the human medinervous system. Hypersalivation cal literature (Table 2).
stimulates swallowing, which stimulates relaxation of the gastroesopha- Phenothiazines
geal sphincter. The bicarbonate-rich Phenothiazines are broad-specsaliva secreted by the salivary glands trum antiemetics that have antidoin the mouth lubricates the esopha- paminergic and antihistaminergic
gus and helps neutralize the stom- properties at low doses in the
ach’s acidic environment before CRTZ and anticholinergic effects at
vomiting.8,13 Before retching, abo- higher doses at other central sites,
ral gastric and esophageal motility including the emetic center.9 These
diminishes and the lower esopha- drugs also block norepinephrine
at peripheral α-adrenergic recepgeal and pyloric sphincters relax.
Retching is the second phase of tors. Drugs in this group include
vomiting and begins with the onset chlorpromazine, prochlor­perazine,
of a retrograde giant contraction.20,21 and acetylpromazine. Common
This contraction is a single-phase, ret- adverse effects in small animals,
rograde, peristaltic motion that emp- especially dogs, include ataxia,
ties the proximal duodenal contents hypotension, and excessive sedainto the stomach.20–22 It is followed by tion. Generalized central nervous
deep inspiratory movements, force- system (CNS) stimulation, aggresful contractions of the abdominal siveness, violent behavior, extrapymuscles and diaphragm, and closure ramidal effects, and seizures are
of the glottis. These actions produce rare. Fluid therapy is indicated in
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patients undergoing phenothiazine therapy
because of the vasodilatory properties of
these drugs.
Anticholinergics
Anticholinergic drugs block cholinergic afferent
pathway transmission from the gastrointestinal tract (peripheral action) and the vestibular
system to the emetic center (central action).9
Scopolamine and isopropamide are centrally acting anticholinergics that cross the blood–brain
table 1
barrier. They have a short duration of action
and can cause excitement in cats. Peripherally
acting anticholinergics include propantheline
and methscopolamine. Isopropamide and propantheline are the drugs in this group that are
most commonly used in small animals for vomiting related to motion sickness.25 Side effects
reported in humans and small animals include
xerostomia (dry mouth), sedation, visual disturbances, drowsiness, dysphoria, confusion, gastrointestinal ileus, and disorientation.9,26
Vomiting Reflex Components, Receptors, and Controlling Neurotransmitters and Medications
Receptor
Receptor Agonists
Receptor Antagonists
Chemoreceptor trigger zone
D2-Dopaminergic
Dopamine
etoclopramide
M
rochlorperazine
P
Trimethobenzamide
Acetylpromazine
Chlorpromazine
aloperidol
H
Droperidol
M1-Cholinergic
Acetylcholine
ropantheline
P
hlorpromazine
C
Isopropamide
Scopolamine
Prochlorperazine
ethscopolamine
M
Acetylpromazine
H1-Histaminergic
Histamine
iphenhydramine
D
rochlorperazine
P
Dimenhydrinate
Chlorpromazine
Meclizine
Acetylpromazine
Promethazine
α2-Adrenergic
Norepinephrine
rochlorperazine
P
Chlorpromazine
ohimbine
Y
Acetylpromazine
5-HT3-Serotonergic
Serotonin
ndansetron
O
Dolasetron
irtazapine
M
Propofol
etoclopramide
M
Granisetron
ENKµ,δ-Enkephalinergic
Met-enkephalin
Leu-enkephalin
Butorphanol
Neurokinin-1 antagonist
Substance P
Maropitant
5-HT1A-Serotonergic
Serotonin
Diphenhydramine
Dimenhydrinate
Meclizine
α2-Adrenergic
Norepinephrine
Prochlorperazine
Chlorpromazine
Yohimbine
Glucocorticoid receptors
Dexamethasone
Cyproterone
Mifepristone
Neurokinin-1 antagonist
Substance P
Maropitant
M1-Cholinergic
Acetylcholine
ropantheline
P
hlorpromazine
C
Isopropamide
Scopolamine
Prochlorperazine
Methscopolamine
Acetylpromazine
H1-Histaminergic
Histamine
iphenhydramine
D
Dimenhydrinate
Meclizine
rochlorperazine
P
Chlorpromazine
Diazepam
yclizine
C
Promethazine
5-HT3-Serotonergic
Serotonin
ndansetron
O
Dolasetron
irtazapine
M
Metoclopramide
Granisetron
Neurokinin-1 antagonist
Substance P
Maropitant
D2-Dopaminergic
Dopamine
etoclopramide
M
rochlorperazine
P
Trimethobenzamide
Acetylpromazine
Chlorpromazine
aloperidol
H
Droperidol
5-HT4-Serotonergic
Cisapride
Metoclopramide
Serotonin
Piboserod
M2-Cholinergic
Acetylcholine
ropantheline
P
Isopropamide
Prochlorperazine
Motilin
Erythromycin
Motilin
QuickNotes
Emetic center
Vomiting is a neurologically mediated
reflex that depends
on neural or
humoral activation
of the emetic center.
Vestibular apparatus
Vagal afferents
Vagal efferents
hlorpromazine
C
Scopolamine
ethscopolamine
M
Acetylpromazine
—
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Antihistamines
Antihistamines can intercept cholinergic and
histaminic nerve transmission responsible for
vestibular stimulation of the vomiting center.25
Drugs in this classification include diphenhydramine, dimenhydrinate, and meclizine.
These drugs display H 1-antihistaminergic
properties and are mainly used to control the
clinical signs of motion sickness. Mild sedation, xerostomia, and drowsiness are some of
the adverse effects. Meclizine can be teratogenic if administered at high doses.25
Cats do not have histamine receptors in the
CRTZ, and antihistaminic drugs do not control
their vomiting.27
Serotonin Antagonists
QuickNotes
Antiemetics are
drugs that block
specific superficial
cell receptor sites,
consequently disrupting the vomiting
reflex.
Serotonin antagonists are specific inhibitors
of 5-HT-serotonergic receptors. They control
vomiting by acting on receptors located on
the periphery of vagal nerve terminals and
centrally on the CRTZ.25,26 These receptors
are normally stimulated by serotonin released
from the enterochromaffin cells of the small
intestine in response to damage to the gastrointestinal mucosa. Ondansetron, a member of
this class of antiemetic drugs, has been shown
to control vomiting in dogs28,29 and is used in
dogs receiving radiation and chemotherapy
when metoclopramide and other antiemetics fail to control vomiting.28,29 Dolasetron,
another member of this group, acts on receptors in the CRTZ.25 Both of these drugs are
used extensively in human medicine, and
they seem to be safe antiemetic alternatives
in veterinary medicine.30,31 However, they are
not effective in controlling vomiting caused by
motion sickness.25,26
Side effects of these drugs that have been
reported in people include electrocardiographic
changes, including PR and QT prolongation and
QRS widening, that are believed to be caused
by sodium channel blockage by dolasetron
metabolites. Diarrhea, headache, dizziness, and
musculoskeletal pain have been reported as
well. These medications can be expensive.
Substituted Benzamides
Substituted benzamides exert antiemetic effects
through different mechanisms. Some, such as
metoclopramide and trimethobenzamide, antagonize dopamine receptors in the CNS and block
5-HT3-serotonergic receptors when administered
126
at high concentrations.9,25 Metoclopramide is
known for its potent dopaminergic antagonism,
but trimethobenzamide, which is also a weak
antihistamine, has not been a very effective antidopaminergic agent clinically. Metoclopramide
has more action on D2-dopaminergic receptors than trimethobenzamide and is 20 times
more potent than phenothiazines.7 As a result,
metoclopramide should not be used in patients
receiving dopamine.12
Cisapride, another substituted benzamide,
activates neuronal 5-HT4 receptors, which
facilitates gastric emptying. Metoclopramide
also activates neuronal 5-HT4 receptors
and blocks 5-HT3 -serotonergic receptors,
increases the lower esophageal sphincter
tone, and enhances aboral gastrointestinal
motility; therefore, these drugs are classified as prokinetics as well.9 Adverse effects
of these drugs include CNS excitement and
behavioral changes, especially during rapid
intravenous administration or if given at high
doses. Metoclopramide controls peripherally
induced and humorally mediated vomiting
due to numerous conditions, but it should
be avoided if gastrointestinal obstruction is
suspected because its prokinetic properties
could predispose these patients to gastric or
intestinal perforation. This contraindication
also applies to cisapride.
Butyrophenone and Benzimidazole
Derivatives
Butyrophenone derivatives (e.g., haloperidol,
droperidol) are potent dopamine antagonists
in the CRTZ and are used as tranquilizers.9
Their side effects are very similar to those of
phenothiazines. The benzimidazole derivatives antagonize dopamine receptors in the
gastrointestinal smooth muscle and display
prokinetic properties like those of metoclo­
pramide,32 but their use in veterinary medicine
is minimal if any.
Opioids
Enkephalins—endogenous opiates belonging to the endorphin family—are believed to
have antiemetic properties. Neurons containing
enkephalins have been identified near the CRTZ
and the emetic center.33 Evidence suggests that
opioid κ and/or μ receptors are present in the
vomiting center and are involved in inhibition
of emesis in dogs and cats.34 Butorphanol, a pri-
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table 2
Most Common Antiemetics Used in Small Animal Medicine
Drugs
Site of Action
Dosage
Side Effects
Prochlorperazinea,13
CRTZ and emetic center
Dogs and cats: 0.1–0.5 mg/kg SC or IM q6–8h
Hypotension, sedation
Chlorpromazinea,2,13
CRTZ and emetic center
Dogs: 0.1–0.5 mg/kg SC, IM, or IV q6–8h
Cats: 0.2–0.5 mg/kg SC, IM, or IV q6–8h
Hypotension, sedation
Yohimbinea,2
CRTZ and emetic center
Dogs: 0.25–0.5 mg/kg SC or IM q12h
Hypotension, sedation
Metoclopramidea,2,13
CRTZ, GI smooth muscle
Dogs: 0.1–0.4 mg/kg PO, SC, or IM q6h
Cats: 0.2–0.4 mg/kg PO, or SC q6–8h
CRI: 1–2 mg/kg/day
Extrapyramidal signs, constipation
Trimethobenzamide2,13
CRTZ
Dogs: 3 mg/kg IM q8–12h
Allergic reactions
Diphenhydraminea,2,13
CRTZ
Dogs and cats: 2–4 mg/kg PO or IM q8h
Sedation, GI effects
Dimenhydrinate
CRTZ
Dogs and cats: 4–8 mg/kg PO q8h
Sedation, GI effects
CRTZ
Dogs and cats: 4 mg/kg PO q24h
Sedation, xerostomia, tachycardia
Propanthelinea
Parasympathetic nervous system
Dogs and cats: 0.25 mg/kg PO q8h
Gastric retention, ileus, tachycardia
Isopropamideb
Parasympathetic nervous system
Dogs and cats: 0.2–0.4 mg/kg PO q8–12h
Gastric retention, ileus, tachycardia
Ondansetrona,2
CRTZ and vagal afferent neurons
Dogs: 0.11–0.176 mg/kg slow IV push q24h
Cats: 0.1–0.15 mg/kg slow IV push q24h
Sedation
Dolasetrona
CRTZ
Dogs: 0.6 mg/kg IV q24h or 0.5 mg/kg PO, SC, or IV q24h
Cats: 0.6 mg/kg IV q12h or 0.6–1 mg/kg PO q12h
Electrocardiogram changes
Mirtazapinea
CRTZ and vagal afferent neurons
Dogs: 0.6 mg/kg PO q24h, not to exceed 30 mg/day
Cats: 3–4 mg/cat PO q72h
Sedation, ataxia, depression, vocalization
CRTZ and emetic center
Dogs: 1 mg/kg SC q24h up to 5 days or 2 mg/kg PO q24h up
to 5 days
Injection site soreness, ataxia, anorexia,
diarrhea
Myenteric neurons
Dogs: 0.1–0.5 mg/kg PO q8h
Cats: 0.1–1.0 mg/kg or 5 mg (total dose) PO q8–12h
None
GI smooth muscle
Dogs and cats: 0.5–1.0 mg/kg IV q8h, up to 5.0 mg/kg PO q8h
Vomiting at antimicrobial doses (15 mg/
kg tid)
Emetic center
Dogs: 0.2–0.4 mg/kg IM 30 min before cisplatin infusion
Sedation, ataxia, anorexia, diarrhea
CRTZ
None reported in veterinary medicine
Apnea, hypotension, seizurelike signs
Emetic center, medulla
Dogs: 0.1 mg/kg SC or IV before chemotherapy
GI ulceration
Vestibular system suppression
0.1–0.2 mg/kg PO q6h
Sedation
α2-Adrenergic antagonists
D2-Dopaminergic antagonists
H1-Histaminergic antagonists
Meclizine
a,2,13
a
M1-Cholinergic antagonists
5-HT3-Serotonergic antagonists
NK1-Neurokinin antagonist
Maropitant40
5-HT4-Serotonergic antagonist
Cisapridea,2
Motilin agonist
Erythromycina,2
Opioid
Butorphanola,13
Others
Propofola
Dexamethasone
Diazepam
a
13
Plumb DC. Veterinarian Drug Handbook. 6th ed. Ames, IA: Wiley-Blackwell; 2008.
b
Richter KP. Treating acute vomiting in dogs and cats. Vet Med 1992;87(8):814-818.
a
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marily κ and σ agonist, is used to prevent vomiting related to cisplatin therapy in dogs.35,36
Neurokinin Antagonists
QuickNotes
Phenothiazines are
broad-spectrum
antiemetics that
have antidopaminergic and antihistaminergic properties
in the CRTZ and
anticholinergic
effects in the emetic
center.
128
Neurokinin (NK1) antagonists are a new group
of antiemetics that includes maropitant, an agent
developed for dogs that acts as a ligand for the
substance P receptors located in many areas
of the brain, including the emetic center and
CRTZ.37 It is believed that the substance P–NK1
receptor complex is in the final common pathway of the neural and humoral pathways of the
vomiting reflex.38 Studies in dogs have showed
that maropitant prevents vomiting caused by
peripheral and central emetogens, including
apomorphine, cisplatin, and syrup of ipecac,39
and clinical conditions such as pancreatitis
and gastroenteritis.39 Maropitant is also effective against vomiting caused by motion sickness.39 Adverse effects reported with this drug
include ataxia, anorexia, diarrhea, and injection
site soreness.40 This drug should not be used in
dogs younger than 16 weeks because bone marrow hypoplasia has been reported.40
Other Drugs
Other drugs used to control vomiting centrally
include yohimbine, diazepam, dexamethasone,
propofol, and mirtazapine. Yohimbine, a pure
α2-adrenergic antagonist, is a very potent antiemetic
used in dogs and cats. It may cause CNS excitement,
excessive sedation, muscle tremors, tachypnea, ptyalism, and hyperemic mucous membranes.36
Diazepam relieves nausea and vomiting in
people.41 Studies with animal models and clinical trials in human medicine suggest that this
drug suppresses the vestibular system.41–43
The antiemetic properties of corticosteroids
are incompletely understood, but their mechanism involves the activation of glucocorticoid
receptors in the medulla, especially the emetic
center in cats.44 Dexamethasone has been
shown to be useful in controlling chemotherapy-associated nausea and vomiting in human
patients45 and dogs.45,46
Propofol, an alkylphenol derivative, is used as
an antiemetic in people with chemotherapy-associated nausea and vomiting that is unresponsive
to serotonin antagonists or dexamethasone.47,48 It
has been proposed that its antiemetic mechanism
involves reduction of the serotonin concentration
in the CRTZ via γ-aminobutyric acid activity and
5-HT3 serotonin receptor antagonism.49
Mirtazapine is a piperazinoazepine drug used
as an antidepressant in people. It antagonizes
central presynaptic α2-receptors and blocks
serotonin receptors.50 It is a weak 5-HT1 serotonin receptor antagonist, a potent 5-HT2 and
5-HT3 sero­tonin receptor antagonist, and an
H1-histamine antagonist.50 It is used to control
chemotherapy-associated nausea and vomiting in
humans50,51 and, more recently, in small animals.
Treatment of Common Vomiting Conditions
Box 1 lists several conditions and diseases that
commonly cause vomiting.
Gastritis or Gastric Ulceration
Treatment to manage vomiting caused by gastritis or gastric ulceration must include proper
fluid therapy and gastric mucosal protection.
Many clinicians use broad-spectrum antiemetics
because they cover local and peripheral receptors. Chlorpromazine, serotonin antagonists, and
metoclopramide are good options. Maropitant
seems to work extremely well in dogs. If vomiting is associated with gastrointestinal ulceration
due to NSAID administration, therapy with
misoprostol, a prostaglandin E1 (PGE) analog,
may be effective in controlling both the ulcerative lesion and vomiting as a secondary problem.52 Proton pump inhibitors and H2-histamine
antagonists provide more complete inhibition of
gastric acid secretion in severe cases of ulceration.12,25,53 If Helicobacter spp are the underlying cause of ulceration, appropriate antibiotic
therapy and antacids should relieve the clinical
signs of the infection.
Patients with neoplastic diseases often have
gastrointestinal ulceration. Mast cell tumors of
any stage, grade, and size can cause vomiting in dogs by increasing the plasma histamine concentration.16,54 Histamine acts on the
CRTZ and the gastric mucosa. Mast cell tumor
ulceration and its effects are treated with
H2-histamine antagonists. Tumor size and histamine release in dogs are controlled with the
administration of corticosteroids.12,55
Pancreatitis
Pancreatitis causes ileus due to intestinal
inflammation, resulting in direct afferent input
to the vomiting center.12 Metoclopramide is the
most common antiemetic used in these patients
because it acts centrally and peripherally. In
dogs, phenothiazines, 5-HT 3 -serotonergic
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antagonists, and maropitant can be useful if
metoclopramide fails to control vomiting.
Emesis caused by cancer chemotherapy and
other drugs (e.g., digitalis) is mediated by
5-HT3-serotonergic receptors.2,12,25 In humans,
the chemotherapeutic drugs most commonly
associated with vomiting include cisplatin,
cyclophosphamide, dacarbazine, and doxorubicin.56 Drugs with 5-HT3-serotonergic antagonist
properties, especially the serotonin antagonists ondansetron, granisetron, dolasetron,
block these receptors in the CRTZ in cats and
in the vagal afferent neurons in dogs.25,26,28,29,57
Metoclopramide is widely used to control
chemotherapy-induced vomiting.6,58 The new
agent maropitant is also effective in controlling
cisplatin-induced vomiting in dogs, and even
though there is coexpression of substance P
with 5-HT receptors in the primate brain,37 this
has not been documented in dogs or cats.
ing inputs from the two vestibular systems (the
semicircular canals and the otolith organs); or
(3) comparison of input from these systems
with the individual’s expectations derived
from previous experiences.59 Vomiting caused
by motion sickness involves M1-cholinergic
and H1-histaminergic receptors,2,11 and treatment should antagonize both receptors.
Phenothiazines like chlorpromazine and
prochlorperazine can antagonize both receptors
at the same time, but diphenhydramine, dimenhydrinate, cyclizine, meclizine, and promethazine are H1-histamine blocking agents only, and
they should be combined with a M1-cholinergic
receptor blocker for effective control of emetic
signals originating from the vestibular apparatus. Maropitant prevents kinetosis in dogs by
blocking the final common pathways of the
vomiting reflex, including signals from the vestibular system.40 Scopolamine is a muscarinic
M1-cholinergic antagonist used to treat motion
sickness, but results are not consistent.
Motion Sickness
Uremia
Motion sickness, or kinetosis, is generated from
the vestibular apparatus.2,9,11 Studies in humans
have revealed that motion sickness is caused by
three mechanisms: (1) conflicting inputs from
the visual and vestibular systems; (2) conflict-
Uremic toxins cause decreased gastrin clearance and irritate the gastrointestinal mucosa,
resulting in ulcerative lesions and gastritis.
When these toxins cross the blood–brain
barrier, they stimulate central and peripheral
receptors and activate D2-dopaminergic receptors in the CRTZ.2,11 Dopamine antagonists
like metoclopramide and chlorpromazine
effectively block these receptors.
Diuresis with appropriate fluid therapy and
a proton pump inhibitor or H2-histaminergic
antagonist helps relieve uremia by diminishing the secretion of hydrogen ions into the
stomach, providing protection and promoting
mucosal healing.
Chemotherapy and Other Drugs
Box 1
Most Common Causes of
Vomiting in Dogs and Cats
bdominal disorders
A
Dietary factors
Disorders of the small and large intestines
Disorders of the stomach
Drugsa
Endocrine disorders
❯ Hypoadrenocorticism
❯ Hypoparathyroidism
Neurologic disorders
Parasitism
❯ Ollulanus tricuspis in cats
❯ Physaloptera
❯ Salmon poisoning (Neorickettsia helminthoeca)
Systemic diseases
Toxins, chemicals, and poisons
a
Almost any drug can cause vomiting, especially if
given orally.
QuickNotes
Vomiting caused
by motion sickness involves
M1-cholinergic and
H1-histaminergic
receptors, and treatment should antagonize both receptors.
Gastrointestinal Motility Disorders
Prokinetics—cisapride, metoclopramide, and
erythromycin—should be used to control vomiting due to nonobstructive delayed gastric
emptying. These drugs exert their effects on
different receptors. Cisapride, the most effective
prokinetic agent available,11 lacks direct antiemetic effects but stimulates 5-HT4-serotonergic
receptors.60 Metoclopramide’s antagonism of
D2-dopaminergic receptors enables it to stimulate motility in areas where these receptors are
present (the higher gastrointestinal tract, lower
esophageal sphincter, stomach, and duode-
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CE Vomiting
QuickNotes
Patients with vomiting of undetermined
etiology must be
treated with the
safest approach
possible once systemic diseases have
been ruled out.
130
num).2,11 Erythromycin, a macrolide used for its
antimicrobial properties, is useful as a prokinetic
at low doses.2,11 In dogs, it stimulates the release
of motilin, which initiates phase III of the migrating myoelectric complex,61,62 the sequence of
motor activity during the interdigestive period in
the small bowel.63 This cyclic pattern originates
in the gastric antrum and extends over the entire
length of the small intestine.62,63 The third and
final phase of this pattern is generally associated
with the propulsion of ingesta.64,65 It is unknown
whether cats can benefit from this effect.
Dogs that vomit bile in the morning before
eating may have bilious vomiting syndrome.
This is a condition characterized by grass ingestion, vomiting, and lack of other definitive clinical signs. It mostly occurs in the morning and
is believed to be commonly associated with
gastritis, inflammatory bowel disease, and bile
and gastroesophageal reflux. Affected patients
usually respond to a single evening dose of
cisapride, metoclopramide, or erythromycin.
References
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Undetermined Etiology
Patients with vomiting of undetermined etiology
must be treated with the safest approach possible once systemic diseases (e.g., liver disease,
renal disease, endocrine disease) have been
ruled out. Patients that are uncomfortable from
excessive vomiting or are at high risk for aspiration pneumonia and have not been exposed to
a toxic agent should be treated with antiemetics
when available. α2-Adrenergic antagonists and
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antagonists have become very popular over the
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be considered if vomiting becomes refractory
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3 CE
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CE Test 1
1.Emesis is initiated, controlled, regulated,
and organized by the
a.higher centers of the brain.
b.CRTZ.
c.vestibular apparatus.
d.emetic center.
2.
The vomiting pathways are controlled by
a.neurotransmitter–receptor interactions.
b.the higher centers of the brain.
c.the peripheral nervous system.
d.vestibular neurons.
3.___________ are considered broadspectrum antiemetics because of their
effect on multiple receptors.
a.Anticholinergics
b.Phenothiazines
c.Serotonin antagonists
d.Opioids
4.Emesis caused by cancer chemotherapy
and other drugs is mediated by
___________ receptors.
a.D2-dopaminergic
b.M1-cholinergic
c.H2-histaminergic
d.5-HT3-serotonergic
5.Which antiemetic is also classified as a
prokinetic?
a.ranitidine
b maropitant
c.metoclopramide
d.propofol
6.Which condition or pathogen is the least
likely to cause gastric ulceration?
a.Helicobacter spp
b.mast cell tumor
c.gastrinoma
d.kinetosis
7.Mirtazapine does not antagonize
___________ receptors.
a.H1-histaminergic
b.5-HT3-serotonergic
c.central presynaptic α2 d.D2-dopaminergic
8.___________ can be used for chemotherapy-associated nausea and/or vomiting,
especially when patients do not respond
to the newer serotonin antagonists and
when multiple medication therapy fails.
a.Propofol
b.Diazepam
c.Mirtazapine
d.Dexamethasone
9.Which antiemetic antagonizes neurokinin receptors in many areas of the brain?
a.mirtazapine
b.maropitant
c.dolasetron
d.prochlorperazine
10. S
elect the correct antiemetic–adverse
effect pair.
a.ondansetron; renal toxicity
b.chlorpromazine; hypotension
c.metoclopramide; sedation
d.meclizine; gastrointestinal perforation
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