Pharmacy Clinic
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Nausea and Vomiting
Vomiting and anti emetics
Vomiting is the forceful expulsion of contents of the stomach and often, the proximal small
intestine. It is a manifestation of a large number of conditions, many of which are not primary
disorders of the gastrointestinal tract. Regardless of cause, vomiting can have serious
consequences, including acid-base disturbance, volume and electrolyte depletion, malnutrition
and aspiration pneumonia.
The Act of Vomiting
Vomiting is usually experienced as the finale in a series of three events, which everyone
reading this has experienced:
• Nausea is an unpleasant and difficult to describe psychic experience in humans and
probably animals. Physiologically, nausea is typically associated with decreased gastric motility
and increased tone in the small intestine. Additionally, there is often reverse peristalsis in the
proximal small intestine.
• Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a
closed glottis. While this is occurring, the antrum of the stomach contracts and the fundus
and cardia relax.
• Emesis or vomiting is when gastric and often small intestinal contents are propelled up
to and out of the mouth. It results from a highly coordinated series of events that could be
described as the following series of steps (don't practice these in public):
o A deep breath is taken, the glottis is closed and the larynx is raised to open the upper
esophageal sphincter. Also, the soft palate is elevated to close off the posterior nares.
o The diaphragm is contracted sharply downward to create negative pressure in the
thorax, which facilitates opening of the esophagus and distal esophageal sphincter.
o Simultaneously with downward movement of the diaphragm, the muscles of the
abdominal walls are vigorously contracted, squeezing the stomach and thus elevating
intragastric pressure. With the pylorus closed and the esophagus relatively open, the route
of exit is clear.
The series of events described seems to be typical for humans, but is not inevitable.
Vomiting occasionally occurs abruptly and in the absence of premonitory signs - this situation
is often referred to as projectile vomiting. A common cause of projectile vomiting is gastric
outlet obstruction, often a result of the ingestion of foreign bodies.
An activity related to but clearly distinct from vomiting is regurgitation, which is the passive
expulsion of ingested material out of the mouth - this often occurs even before the ingestion
has reached the stomach and is usually a result of esophageal disease. Regurgitation also is
a normal component of digestion in ruminants (حيوان المجتر)
There is also considerable variability among species in the propensity for vomiting. Rats
reportedly do not vomit. Cattle and horses vomit rarely - this is usually an ominous sign and
most frequently a result of acute gastric distension. Carnivores such as dogs and cats vomit
frequently, often in response to such trivial stimuli as finding themselves on a clean carpet.
Humans fall between these extremes, and interestingly, rare individuals have been identified
that seem to be incapable of vomiting due to congenital abnormalities in the vomiting centers
of the brainstem.
Control of Vomiting
The complex, almost stereotypical set of activities that culminate in vomiting suggest that
control is central, which indeed has been shown to be true. Within the brainstem are two
anatomically and functionally distinct units that control vomiting:
Bilateral vomiting centers in the reticular formation of the medulla integrate signals from a
large number of outlying sources and their excitement is ultimately what triggers vomiting.
Electric stimulation of these centers induces vomiting, while destruction of the vomiting
centers renders vomiting. The vomiting centers receive afferent signals from at least four
major sources:
• The chemoreceptor trigger zone: The chemoreceptor trigger zone is a bilateral set of
centers in the brainstem lying under the floor of the fourth ventricle. Electrical stimulation of
these centers does not induce vomiting, but application of emetic drugs does - if and only if
the vomiting centers are intact.
The chemoreceptor trigger zones function as emetic chemoreceptors for the vomiting centers
- chemical abnormalities in the body (e.g. emetic drugs, uremia, hypoxia and diabetic
ketoacidosis) are sensed by these centers, which then send excitatory signs to the vomiting
centers. Many of the antiemetic drugs act at the level of the chemoreceptor trigger zone.
• Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) -
these signals inform the brain of such conditions as gastrointestinal distention (a very potent
stimulus for vomiting) and mucosal irritation.
• Visceral afferents from outside the gastrointestinal tract - this includes signals from
bile ducts, peritoneum, heart and a variety of other organs. These inputs to the vomiting
center help explain how, for example, a stone in the common bile duct can result in vomiting.
• Afferents from extramedullary centers in the brain - it is clear that certain psychic
stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral trauma can
result in vomiting.
Two basic sets of pathways - one neural and one humoral - lead to activation of centers in
the brain that initiate and control vomiting. Think of the vomiting centers as commander in
chief of vomiting, who makes the ultimate decision. This decision is based on input from a
battery of advisors, among whom the chemoreceptor trigger zone has considerable influence.
This straightforward picture is almost certainly oversimplified and flawed in some details, but
helps to explain much of the physiology and pharmacology of vomiting.
General risk factors and etiologies
Cancer; not all cancer patients will experience nausea and/or vomiting. The most
common causes are emetogenic chemotherapy drugs and radiation therapy to the
gastrointestinal tract, liver, or brain. Several patient characteristics have also been identified.
These include incidence and severity of nausea and vomiting (N&V) during past courses of
chemotherapy, history of chronic alcohol use, age, and gender. Patients with poor control of
N&V during prior chemotherapy cycles are likely to experience N&V in subsequent cycles. N&V
is less likely in patients with a history of chronic, high alcohol intake, and more likely in women
and younger patients (<50 years).
Fluid and electrolyte imbalances such as hypercalcemia, volume depletion, or water
intoxication
Tumor invasion or growth in the gastrointestinal tract, liver, or central nervous
system, especially the posterior fossa
Constipation
Certain drugs such as
o Digoxin
o Theophylline
o Dopaminergic agonists (Levodopa, bromocriptine, apomorphine)
o Opioids
o NSAIDs
o Salicylates
o AntibioticsInfection or septicemia; or uremia
Chemotherapy:
Acute Chemotherapy Induced Nausea and Vomiting
(1) Initially rule out other causes
(2) Evaluate emetogenic potential of chemotherapeutic regimen.
(3) Generally 5 classes of agents:
o Classes of regimens/agents
o Very High emetic incidence ie >90%
o High emetic incidence ie 60-90%
o Moderate emetic incidence ie 30-60%
o Low emetic incidence ie 10-30%
o Very Low emetic incidence ie < 10%
o Also can be classified as mild, moderate and severe emetogenic potential
The psychological variables of state anxiety, (level of anxiety during chemotherapy
infusions), and pretreatment expectations for nausea and vomiting (self-fulfilling prophecy)
have also been investigated as predictors of post-treatment nausea
Odors
Tastes
Noxious stimuli (visual, physical)
Irritants - swallowed
Complications with Emesis
1. Severe Medical Complications
- Dehydration
- Electrolyte/Acid Base Imbalance
- Malnutrition
- Esophageal and mucosal tears (eg Mallory-Weiss)
- Aspiration pneumonia
- Pathological fractures
- Dental Caries
2. Patient discomfort and loss of quality of life
3. Non-compliance with treatment regimen
Vomiting is the forceful expulsion of contents of the stomach and often, the proximal small
intestine. It is a manifestation of a large number of conditions, many of which are not primary
disorders of the gastrointestinal tract. Regardless of cause, vomiting can have serious
consequences, including acid-base disturbance, volume and electrolyte depletion, malnutrition
and aspiration pneumonia.
The Act of Vomiting
Vomiting is usually experienced as the finale in a series of three events, which everyone
reading this has experienced:
• Nausea is an unpleasant and difficult to describe psychic experience in humans and
probably animals. Physiologically, nausea is typically associated with decreased gastric motility
and increased tone in the small intestine. Additionally, there is often reverse peristalsis in the
proximal small intestine.
• Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a
closed glottis. While this is occurring, the antrum of the stomach contracts and the fundus
and cardia relax.
• Emesis or vomiting is when gastric and often small intestinal contents are propelled up
to and out of the mouth. It results from a highly coordinated series of events that could be
described as the following series of steps (don't practice these in public):
o A deep breath is taken, the glottis is closed and the larynx is raised to open the upper
esophageal sphincter. Also, the soft palate is elevated to close off the posterior nares.
o The diaphragm is contracted sharply downward to create negative pressure in the
thorax, which facilitates opening of the esophagus and distal esophageal sphincter.
o Simultaneously with downward movement of the diaphragm, the muscles of the
abdominal walls are vigorously contracted, squeezing the stomach and thus elevating
intragastric pressure. With the pylorus closed and the esophagus relatively open, the route
of exit is clear.
The series of events described seems to be typical for humans, but is not inevitable.
Vomiting occasionally occurs abruptly and in the absence of premonitory signs - this situation
is often referred to as projectile vomiting. A common cause of projectile vomiting is gastric
outlet obstruction, often a result of the ingestion of foreign bodies.
An activity related to but clearly distinct from vomiting is regurgitation, which is the passive
expulsion of ingested material out of the mouth - this often occurs even before the ingestion
has reached the stomach and is usually a result of esophageal disease. Regurgitation also is
a normal component of digestion in ruminants (حيوان المجتر)
There is also considerable variability among species in the propensity for vomiting. Rats
reportedly do not vomit. Cattle and horses vomit rarely - this is usually an ominous sign and
most frequently a result of acute gastric distension. Carnivores such as dogs and cats vomit
frequently, often in response to such trivial stimuli as finding themselves on a clean carpet.
Humans fall between these extremes, and interestingly, rare individuals have been identified
that seem to be incapable of vomiting due to congenital abnormalities in the vomiting centers
of the brainstem.
Control of Vomiting
The complex, almost stereotypical set of activities that culminate in vomiting suggest that
control is central, which indeed has been shown to be true. Within the brainstem are two
anatomically and functionally distinct units that control vomiting:
Bilateral vomiting centers in the reticular formation of the medulla integrate signals from a
large number of outlying sources and their excitement is ultimately what triggers vomiting.
Electric stimulation of these centers induces vomiting, while destruction of the vomiting
centers renders vomiting. The vomiting centers receive afferent signals from at least four
major sources:
• The chemoreceptor trigger zone: The chemoreceptor trigger zone is a bilateral set of
centers in the brainstem lying under the floor of the fourth ventricle. Electrical stimulation of
these centers does not induce vomiting, but application of emetic drugs does - if and only if
the vomiting centers are intact.
The chemoreceptor trigger zones function as emetic chemoreceptors for the vomiting centers
- chemical abnormalities in the body (e.g. emetic drugs, uremia, hypoxia and diabetic
ketoacidosis) are sensed by these centers, which then send excitatory signs to the vomiting
centers. Many of the antiemetic drugs act at the level of the chemoreceptor trigger zone.
• Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) -
these signals inform the brain of such conditions as gastrointestinal distention (a very potent
stimulus for vomiting) and mucosal irritation.
• Visceral afferents from outside the gastrointestinal tract - this includes signals from
bile ducts, peritoneum, heart and a variety of other organs. These inputs to the vomiting
center help explain how, for example, a stone in the common bile duct can result in vomiting.
• Afferents from extramedullary centers in the brain - it is clear that certain psychic
stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral trauma can
result in vomiting.
Two basic sets of pathways - one neural and one humoral - lead to activation of centers in
the brain that initiate and control vomiting. Think of the vomiting centers as commander in
chief of vomiting, who makes the ultimate decision. This decision is based on input from a
battery of advisors, among whom the chemoreceptor trigger zone has considerable influence.
This straightforward picture is almost certainly oversimplified and flawed in some details, but
helps to explain much of the physiology and pharmacology of vomiting.
General risk factors and etiologies
Cancer; not all cancer patients will experience nausea and/or vomiting. The most
common causes are emetogenic chemotherapy drugs and radiation therapy to the
gastrointestinal tract, liver, or brain. Several patient characteristics have also been identified.
These include incidence and severity of nausea and vomiting (N&V) during past courses of
chemotherapy, history of chronic alcohol use, age, and gender. Patients with poor control of
N&V during prior chemotherapy cycles are likely to experience N&V in subsequent cycles. N&V
is less likely in patients with a history of chronic, high alcohol intake, and more likely in women
and younger patients (<50 years).
Fluid and electrolyte imbalances such as hypercalcemia, volume depletion, or water
intoxication
Tumor invasion or growth in the gastrointestinal tract, liver, or central nervous
system, especially the posterior fossa
Constipation
Certain drugs such as
o Digoxin
o Theophylline
o Dopaminergic agonists (Levodopa, bromocriptine, apomorphine)
o Opioids
o NSAIDs
o Salicylates
o AntibioticsInfection or septicemia; or uremia
Chemotherapy:
Acute Chemotherapy Induced Nausea and Vomiting
(1) Initially rule out other causes
(2) Evaluate emetogenic potential of chemotherapeutic regimen.
(3) Generally 5 classes of agents:
o Classes of regimens/agents
o Very High emetic incidence ie >90%
o High emetic incidence ie 60-90%
o Moderate emetic incidence ie 30-60%
o Low emetic incidence ie 10-30%
o Very Low emetic incidence ie < 10%
o Also can be classified as mild, moderate and severe emetogenic potential
The psychological variables of state anxiety, (level of anxiety during chemotherapy
infusions), and pretreatment expectations for nausea and vomiting (self-fulfilling prophecy)
have also been investigated as predictors of post-treatment nausea
Odors
Tastes
Noxious stimuli (visual, physical)
Irritants - swallowed
Complications with Emesis
1. Severe Medical Complications
- Dehydration
- Electrolyte/Acid Base Imbalance
- Malnutrition
- Esophageal and mucosal tears (eg Mallory-Weiss)
- Aspiration pneumonia
- Pathological fractures
- Dental Caries
2. Patient discomfort and loss of quality of life
3. Non-compliance with treatment regimen
| Natural remedies for motion sickness Nausea fact sheet Management of nausea and vomiting Antiemetics in pregnancy PDF |