3205 - Milano, Duomo - Giorgio Bonola - Miracolo di Marco Spagnolo (1681) - Foto Giovanni Dall'Orto, 6-Dec-2007-cropped

Cancer and nausea are associated in about fifty percent of people affected by

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. This may be as a result of the cancer itself, or as an effect of the treatment such as

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...

, or other medication such as

opiates An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonist ...

used for pain relief. About 70 to 80% of people undergoing chemotherapy experience

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

. Nausea and vomiting may also occur in people not receiving treatment, often as a result of the disease involving the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

, or as a result of

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

. Nausea and vomiting may be experienced as the most unpleasant side effects of cytotoxic drugs and may result in patients delaying or refusing further radiotherapy or chemotherapy. The strategies of management or therapy of nausea and vomiting depend on the underlying causes. Medical treatments or conditions associated with a high risk of nausea and/or vomiting include chemotherapy, radiotherapy and malignant bowel obstruction. Anticipatory nausea and vomiting may also occur. Nausea and vomiting may lead to further medical conditions and complications including:

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...

, and a decrease in

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

. Nausea may be defined as an unpleasant sensation of the need to vomit. It may be accompanied by symptoms such as salivation, feeling faint, and a

fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (s ...

. Vomiting is the forceful ejection of stomach contents through the mouth. Although nausea and vomiting are closely related, some patients experience one symptom without the other and it may be easier to eliminate vomiting than nausea. The vomiting reflex (also called emesis) is thought to have evolved in many animal species as a protective mechanism against ingested

toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849� ...

. In humans, the vomiting response may be preceded by an unpleasant sensation termed nausea, but nausea may also occur without vomiting. The

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

is the primary site where a number of emetic stimuli (input) are received, processed and efferent signals (output) are generated as a response and sent to various effector organs or tissues, leading to processes that eventually end in vomiting. The detection of emetic stimuli, the central processing by the brain and the resulting response by organs and tissues that lead to nausea and vomiting are referred to as the emetic pathway or emetic arch.

Causes

Some medical conditions that arise as a result of cancer or as a complication of its treatment are known to be associated with a high risk of nausea and/or vomiting. These include malignant bowel obstruction (MBO), chemotherapy-induced nausea and vomiting (CINV), anticipatory nausea and vomiting (ANV), and radiotherapy-induced nausea and vomiting (RINV).

Malignant bowel obstruction

Malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

bowel obstruction (MBO) of the gastrointestinal tract is a common complication of advanced cancer, especially in patients with bowel or gynaecological cancer. These include

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

, and

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

. Three percent of all advanced cancers lead to malignant bowel obstruction and 25 to 50 percent of patients with ovarian cancer experience at least one episode of malignant bowel obstruction. The mechanisms of action that may lead to nausea in MBO include mechanical compression of the gut, motility disorders, gastrointestinal secretion accumulation, decreased gastrointestinal absorption, and inflammation. Bowel obstruction and the resulting nausea may also occur as a result of anti-cancer therapy such as radiation, or

adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can ...

after surgery. Impaired gastric emptying as a result of bowel obstruction may not respond to drugs alone, and surgical intervention is sometimes the only means of symptom relief. Some constipating drugs used in cancer therapy such as

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

s may cause a slowing of

peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whi ...

of the gut, which may lead to a functional bowel obstruction.

Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects of chemotherapy and is associated with a significant deterioration in quality of life. CINV is classified into three categories: * early onset (occurring within 24 hours of initial exposure to chemotherapy) * delayed onset (occurring 24 hours to several days after treatment) * anticipatory (triggered by taste, odor, sight, thoughts, or anxiety) Risk factors that predict the occurrence and severity of CINV include sex and age, with females, younger people and people who have a high pretreatment expectation of nausea being at a higher risk, while people with a history of high alcohol consumption being at a lower risk. Other person-related variables, such as chemotherapy dose, rate and route of administration, hydration status, prior history of CINV, emesis during pregnancy or motion sickness, tumour burden, concomitant medication and medical conditions also play a role in the degree of CINV experienced by a person. By far the most important factor which determines the degree of CINV is the emetogenic potential of the chemotherapeutic agents used. Chemotherapeutic agents are classified into four groups according to their degree of emetogenicity: high, moderate, low and minimal. The European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) in 2010 as well as the

American Society of Clinical Oncology The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus Go ...

(ASCO) (2011) recommend a

prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

to prevent acute vomiting and nausea following chemotherapy with high emetic risk drugs by using a three-drug regimen including a 5-HT3 receptor antagonist,

dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...

and

aprepitant Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and de ...

(a neurokinin-1 antagonist) given before chemotherapy.

Anticipatory

A common consequence of cancer treatment is the development of anticipatory nausea and vomiting (ANV). This kind of nausea is usually elicited by the re-exposure of the patients to the clinical context they need to attend to be treated. Approximately 20% of people undergoing chemotherapy are reported to develop anticipatory nausea and vomiting. Once developed, ANV is difficult to control by pharmacological means.

Benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s are the only drugs that have been found to reduce the occurrence of ANV but their efficacy decreases with time. Recently, clinical trials suggests that cannabidiolic acid suppresses conditioned gaping (ANV) in shrews. Because ANV is widely believed to be a learned response, the best approach is to avoid the development of ANV by adequate

and treatment of acute vomiting and nausea from the first exposure to therapy. Behavioral treatment techniques, such as systematic desensitization,

progressive muscle relaxation Progressive muscle relaxation (PMR) is a non-pharmacological method of deep muscle relaxation, based on the premise that muscle tension is the body's psychological response to anxiety-provoking thoughts and that muscle relaxation blocks anxiety. ...

and

hypnosis Hypnosis is a human condition involving focused attention (the selective attention/selective inattention hypothesis, SASI), reduced peripheral awareness, and an enhanced capacity to respond to suggestion.In 2015, the American Psychologica ...

have been shown to be effective against ANV.

Radiation therapy

The incidence and severity of radiation therapy-induced nausea and vomiting (RINV) depends on a number of factors including therapy related factors such as irradiated site, single and total dose, fractionation, irradiated volume and radiotherapy techniques. Also involved are person related factors such as gender, general health of the person, age, concurrent or recent chemotherapy, alcohol consumption, previous experience of nausea, vomiting, anxiety as well as the tumor stage. The emetogenic potential of radiotherapy is classified into high, moderate, low and minimal risk depending on the site of irradiation: * High risk:

total body irradiation Total body irradiation (TBI) is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. As the name implies, TBI involves irradiation of the entire body, though in mode ...

(TBI) is associated with a high risk of RINV * Moderate risk: radiation of the upper

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...

, half body irradiation and upper body irradiation * Low risk: radiation of the

cranium The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, th ...

, spine, head and neck, lower thorax region and pelvis * Minimal risk: radiation of extremities and breast

Pathophysiology

Nausea and vomiting may have a number of causes in people with cancer. While more than one cause may exist in the same person stimulating symptoms via more than one pathway, the actual cause of nausea and vomiting may be unknown in some people. The underlying causes of nausea and vomiting may in some cases not be directly related to the cancer. The causes may be categorized as disease-related and treatment-related. The stimuli which lead to emesis are received and processed in the brain. It is thought that a number of loosely organized

neuronal network A neural circuit is a population of neurons interconnected by synapses to carry out a specific function when activated. Neural circuits interconnect to one another to form large scale brain networks. Biological neural networks have inspired the ...

s within the

medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (invol ...

probably interact to coordinate the emetic reflex. Some of the

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...

nuclei which have been identified as important in the coordination of the emetic reflex include the parvicellular reticular formation, the Bötzinger complex and the nucleus tractus solitarii. The nuclei coordinating emesis had formerly been referred to as the vomiting complex, but it is no longer thought to represent a single anatomical structure. Efferent outputs which transmit the information from the brain leading to the motoric response of retching and vomiting include vagal efferents to the

esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to t ...

, stomach and intestine as well as spinal somatomotor neurones to the abdominal muscles and phrenic motor neurones (C3–C5) to the

diaphragm Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...

. Autonomic efferents also supply the heart and airways (vagus), salivary glands (

chorda tympani The chorda tympani is a branch of the facial nerve that originates from the taste buds in the front of the tongue, runs through the middle ear, and carries taste messages to the brain. It joins the facial nerve (cranial nerve VII) inside the fa ...

) and skin and are responsible for many of the

prodromal In medicine, a prodrome is an early sign or symptom (or set of signs and symptoms) that often indicates the onset of a disease before more diagnostically specific signs and symptoms develop. It is derived from the Greek word ''prodromos'', meaning ...

signs such as salivation and skin pallor. Nausea and vomiting may be initiated by various stimuli, through different neuronal pathways. A stimulus may act on more than one pathway. Stimuli and pathways include: * Toxic substances in the gastrointestinal tract:

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a sub ...

substances (including

drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalati ...

which are used in the treatment of cancer) in the lumen of the gastrointestinal tract stimulate vagal afferent nerves in the gut mucosa which communicate to the nucleus ''tractus solitarii'' and the

area postrema The area postrema, a paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its dual role to detect circulating chemical messengers in the blood and t ...

to initiate vomiting and nausea. A number of

receptor Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

s on the terminal ends of the vagal afferent nerves have been identified as being involved in this process, including the 5-hydroxytryptamine3 (5-HT3), neurokinin-1, and cholecystokinin-1 receptors. Various local mediators located in

enterochromaffin cells Enterochromaffin (EC) cells (also known as Kulchitsky cells) are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal re ...

of the gut mucosa play a role in stimulating these receptors. Of these 5-hydroxytryptamine seems to play the dominating role. This pathway has been postulated to be the mechanism by which some anti-cancer drugs such as

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...

induce emesis. * Toxic substances in the blood: toxic substances which have been absorbed into the blood (including cytostatics) or

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

toxic (waste) material released by body or cancer cells into the blood can be detected directly in the

of the brain and trigger the emetic reflex. The area postrema is a structure located on the floor of the

fourth ventricle The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...

around which the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

is permeable, thus allowing for the detection of humoral or pharmacological stimuli in the blood or

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

. This structure contains receptors which form a

chemoreceptor trigger zone The chemoreceptor trigger zone (CTZ) is an area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting. The CTZ is located within the area ...

. Some of the receptors and neurotransmitters involved in the regulation of this emetic pathway include dopamine type D2,

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

types 2–4 (5HT2–4),

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

type 1(H1), and

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

(muscarinic receptors type 1 to 5, M1–5). Some other receptors such as

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clo ...

cannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

type 1 (CB1) and the endogenous opioids may also be involved. * Pathological conditions of the gastrointestinal tract: diseases and pathological conditions of the GIT may also lead to nausea and vomiting through direct or indirect stimulation of the above named pathways. Such conditions may include malignant

bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs ...

, hypertrophic pyloric stenosis and

gastritis Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possi ...

. Pathological conditions in other organs which are linked to the above named emetic pathways may also lead to nausea and vomiting, such as the

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

(through stimulation of cardiac vagal afferents) and

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. * Stimulation of the central nervous system: certain stimuli of the central nervous system may induce the emetic reflex. These include

fear Fear is an intensely unpleasant emotion in response to perceiving or recognizing a danger or threat. Fear causes physiological changes that may produce behavioral reactions such as mounting an aggressive response or fleeing the threat. Fear ...

anticipation Anticipation is an emotion involving pleasure or anxiety in considering or awaiting an expected event. Anticipatory emotions include fear, anxiety, hope and trust. When the anticipated event fails to occur, it results in disappointment (if posit ...

brain trauma A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic br ...

and increased

intra-cranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. T ...

. Of particular relevance to cancer patients in this regard are the stimuli of fear and anticipation. Evidence suggests that cancer patients may develop the side effects of nausea and vomiting in anticipation of chemotherapy. In some patients, re-exposure to cues such as smell, sounds or sight associated with the clinic or previous treatment may evoke anticipatory nausea and vomiting. * Pathological conditions of the vestibular system: a disturbance of the

vestibular system The vestibular system, in vertebrates, is a sensory system that creates the sense of balance and spatial orientation for the purpose of coordinating movement with balance. Together with the cochlea, a part of the auditory system, it constitut ...

such as in

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include de ...

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initi ...

can induce the emetic reflex. Such disturbances of the vestibular system could also be cancer related such as in cerebral or vestibular secondaries (

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...

), or cancer treatment related such as the use of opioids.

Management

The strategies of management or prevention of nausea and vomiting depend on the underlying causes, whether they are reversible or treatable, stage of the illness, the person's prognosis and other person specific factors. Anti emetic drugs are chosen according to previous effectiveness and side effects.

Medication

Drugs that are used in the prophylaxis and therapy of nausea and vomiting in cancer include: *

5-HT3 antagonist The 5-HT3 antagonists, informally known as "setrons", are a class of drugs that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain. With th ...

s: 5-HT3 antagonists produce their anti emetic effect by blocking of the amplifying effect of

on peripheral and central

5-HT3 receptor The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs) and therefore differs structurally and functionally from all other 5-HT receptors (5-hydroxytryptamine, or serotonin receptors) which are G protein-coupled ...

s located on the various vagal afferent nerve endings and the

. They are effective in the treatment and prophylaxis of CINV as well as in malignant bowel obstruction and kidney failure which are associated with elevated serotonin levels. These substances include

Dolasetron Dolasetron (trade name Anzemet) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center i ...

Granisetron Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the ...

Ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery. It is also effective for treating gastroenteritis. It can be given by ...

Palonosetron Palonosetron, sold under the brand name Aloxi, is used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist. Palonosetron is administered intravenously, or as a single oral capsule. Freel ...

, and

Tropisetron Tropisetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia. It was patented in 1982 ...

. They are often used in combination with other anti emetic drugs in people with high risk of emesis or nausea and are recommended as the most effective anti emetics in the prophylaxis of acute CINV. *

Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

: such as

Dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...

are used in the treatment of emesis as a result of chemotherapy, malignant bowel obstruction, raised intracranial pressure and in the chronic nausea of advanced cancer, though their exact mode of action remain unclear. Dexamethason is recommended for use in the acute prevention of highly, moderately, and low emetogenic chemotherapy and in combination with aprepitant for the prevention of delayed emesis in highly emetogenic chemotherapy. *

NK1 receptor antagonist Neurokinin 1 (NK1) antagonists (-pitants) are a novel class of medications that possesses unique antidepressant, anxiolytic, and antiemetic properties. NK-1 antagonists boost the efficacy of 5-HT3 antagonists to prevent nausea and vomiting. The di ...

s: such as

Aprepitant Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and de ...

block the NK1 receptor in the brainstem and gastrointestinal tract. Their antiemetic activity when added to a 5-HT3 receptor antagonist plus dexametasone has been shown in several phase II double-blind studies. *

Cannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

: are a useful adjunct to modern anti emetic therapy in selected patients. They show a combination of weak anti emetic efficacy with potentially beneficial side effects such as sedation and euphoria. However, their usefulness is generally limited by the high incidence of toxic effects, such as dizziness, dysphoria, and hallucinations. Some studies have shown that cannabinoids are slightly better than conventional anti emetics such as

metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...

phenothiazines Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. Th ...

and

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

in the prevention of nausea and vomiting. Cannabinoids are an option in affected people who are intolerant or refractory to 5-HT3 antagonists or steroids and aprepitant as well as in refractory nausea and vomiting and rescue anti emetic therapy. * Prokinetic agents such as

Metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...

Dopamine receptor antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have f ...

s such as Phenothiazines ( Prochlorperazine and

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is t ...

, and

Levomepromazine Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic (approximately half as potent as chlorpr ...

, block D2 receptors found in the chemoreceptor trigger zone * Antihistaminic agents like

Promethazine Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...

block H1 receptors in the vomiting center of the medulla, the vestibular nucleus, and the chemoreceptor trigger zone *

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

agents such as

Scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomi ...

(Hyoscine) are used as anti emetics as they relax smooth muscle and reduce gastrointestinal secretions by blockade of

muscarinic receptors Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

. They may be useful in the management of terminal bowel obstruction *

Somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-cou ...

analoga such as Octreotide are used for the palliation of malignant bowel obstruction, especially when there is high output vomiting not responding to other measures *

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD in ...

is used as a palliative treatment (non-curative symptomatic treatment) and improves numerous symptoms that frequently appear during chemotherapy like nausea, vomiting, loss of appetite, physical pain or insomnia. Due to the large number of cannabinoid receptors ( CB1 and CB2 ) distributed throughout the gastrointestinal tract ( GI ), these substances can help to control and treat many GI diseases where vomiting and nausea are frequent.

Other measures

Other non-drug measures may include: * Diet: Small palatable meals are normally tolerated better than big meals in people affected by nausea and vomiting in cancer. Carbohydrate meals are better tolerated than spicy, fatty and sweet foods. Cool, fizzy drinks are found to be more palatable than still or hot drinks. * The avoidance of environmental stimuli, such as sights, sounds, or smells that may initiate nausea. * Behavioral approaches, such as distraction,

relaxation training A relaxation technique (also known as relaxation training) is any method, process, procedure, or activity that helps a person to relax; to attain a state of increased calmness; or otherwise reduce levels of pain, anxiety, stress or anger. Rela ...

and

Cognitive behavioural therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...

may also be useful. * Alternative medicine:

Acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientif ...

and

ginger Ginger (''Zingiber officinale'') is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice and a folk medicine. It is a herbaceous perennial which grows annual pseudostems (false stems made of the rolled bases of ...

have been shown to have some anti emetic effects on chemotherapy-induced emesis and anticipatory nausea, but have not been evaluated in the nausea of far advanced disease.

Palliative surgery

Palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...

is the active care of people with advanced, progressive illness such as cancer. The World Health Organization (WHO) defines it as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems (such as nausea or vomiting), physical, psychosocial, and spiritual. Sometimes it is possible or necessary to provide relief for cancer caused nausea and vomiting through palliative surgical intervention. Surgery is however not routinely carried out when there are poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

. The surgical approach proves beneficial in affected people with operable lesions, a life expectancy greater than 2 months and good performance status. Often a malignant bowel obstruction is the cause of the symptoms in which case the purpose of palliative surgery is to relieve the symptoms of bowel obstruction by means of several procedures including: *

Stoma In botany, a stoma (from Greek ''στόμα'', "mouth", plural "stomata"), also called a stomate (plural "stomates"), is a pore found in the epidermis of leaves, stems, and other organs, that controls the rate of gas exchange. The pore is bo ...

formation * Bypass of the obstruction * Resection of bowel segments * Placement of

stent In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...

s. *

Percutaneous endoscopic gastrostomy Percutaneous endoscopic gastrostomy (PEG) is an endoscopic medical procedure in which a tube (PEG tube) is passed into a patient's stomach through the abdominal wall, most commonly to provide a means of feeding when oral intake is not adequate ( ...

(PEG) tube placement to enable gastric venting. * Gastric venting through a

nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...

is a semi-invasive possibility for palliation of nausea and vomiting due to gastrointestinal obstruction in people with abdominal malignancies who decline surgery or where surgery may not be indicated. However nasogastric tubes are not recommended to be used over a long period of time because of the high risk of displacement, poor tolerance, restrictions in daily routine activities, coughing, clearing pulmonary secretions and can be cosmetically unacceptable and confining. Complications of nasogastric tubes include aspiration,

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...

, gastric erosion,

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...

and

otitis Otitis is a general term for inflammation or infection, inner ear infection, middle ear infection of the ear, in both humans and other animals. When infection is present, it may be viral or bacterial. When inflammation is present due to fluid bui ...

Epidemiology

12.7 million new cancer cases and 7.6 million cancer deaths were estimated worldwide in 2008. * Nausea or vomiting occur in 50 to 70% of people with advanced cancer. * 50 to 80% of people undergoing radiotherapy experience nausea and/or vomiting, depending on the site of irradiation. * Anticipatory nausea and vomiting is experienced by approximately 20 to 30% of people undergoing chemotherapy. * Chemotherapy-induced nausea and vomiting resulting from treatment with highly emetogenic cytotoxic drugs can be prevented or effectively treated in 70 to 80% of affected people.

References

{{Portal bar, Medicine Oncology Cancer Symptoms and signs: Digestive system and abdomen Vomiting

Causes

Malignant bowel obstruction

Chemotherapy

Anticipatory

Radiation therapy

Pathophysiology

Management

Medication

Other measures

Palliative surgery

Epidemiology

See also

References