Prevention and treatment of CINV in adult patients receiving cancer chemotherapy will be reviewed here. The pathophysiology of CINV is. A range of non-drug treatment strategies exist for the management of CINV, including lifestyle. With the correct use of antiemetics, CINV can be prevented in almost 70% to up to 80% of patients. Treatment guidelines are useful tools that enable physicians.
Treated? CINV and It Is What Is How
Serotonin receptor antagonists So-called serotonin receptor antagonists have formed part of treatment since the beginning of the s. Serotonin receptors antagonists are effective against nausea and vomiting on the day chemotherapy is administered. Neurokinin receptor antagonists Another class of medication is so-called neurokinin receptor antagonists. They block the effect of the substance P neurotransmitter, being used in both highly and moderately emetic chemotherapy both in the acute phase of vomiting and the combination with serotonin receptor antagonists and steroids, as well as in the delayed phase in which it is usually only administered together with steroids.
Steroids The general title of steroids refers to cortisone derivatives which strengthen the effect of other anti-emetic medication when used in combination with them. If the aforementioned standard treatment against nausea and vomiting does not work, other medication may be used. This includes cannabinoids, dopamine antagonists, benzodiazepine, neuroleptics and antihistamines. Cannabinoids Cannabinoids work via cannabinoid receptors in the body.
How cannabinoids work has not yet fully been established, but thanks to the occupation and activation of the CB1 receptor e. This ultimately leads to clinical effects such as the prevention of vomiting, a reduction in the sensation of pain or an increase in appetite.
Further information on nausea and vomiting during cancer treatment can be found under German website: Krebsinformationsdienst vom Deutsches Krebsforschungszentrum. The CTZ is a highly vascular organ that is not confined to the blood-brain barrier and is therefore vulnerable to exposure to chemotherapy from the blood as well as cerebral spinal fluid Wickham, Activation of the VC directly or through the CTZ results in stimulation of the salivation and respiratory centers as well as control of the pharyngeal, GI and abdominal muscles.
Noradrenaline, somatostatin, enkephalin, acetylcholine, aminobutyric acid, vasopressin and cortisol can also induced vomiting through the CTZ. Though the VC has many neurotransmitter receptors it is most sensitive to muscarinic and dopamine Murphy-Ende, Research has primarily focused on the pathophysiology of acute and delayed CINV, thus the pathophysiology of nausea as a sole entity is less known.
It is thought that nausea is mediated by the autonomic nervous system. Nausea can be described as an unpleasant or queasy feeling causing a desire to vomit. It is important to note that nausea is not always accompanied by vomiting. Clinical manifestations that may accompany nausea include tachycardia, perspiration, light-headedness, dizziness, pallor, excess salivation, anorexia and weakness. Nausea and vomiting in cancer patients can be multi-factorial.
Evaluation of symptoms should reflect this. Nausea and vomiting can have structural, psychological, chemical, metabolic or a combination of origins. When evaluating cancer patients with suspected CINV, causes such as pain, anxiety, hepatosplenomegaly, bowel obstruction, metastasis or increased ICP should also be considered. Immunocompromised and elderly patients should also be evaluated for bacterial or viral gastroenteritis as these populations may be more vulnerable to an infectious process.
It is crucial to illicit onset and duration as well as any potential associated, aggravating or relieving symptoms. Bowel Obstruction Hepatosplenomegaly Brain metastasis. Oncology nurses possess the ability to educate patients undergoing potentially emetogenic therapy regarding possible risks and risk modifications, non-pharmacologic treatment and potential side effects from prescribed antiemetics. Assessment, communication and education are key nursing roles in the successful treatment of CINV.
These startling statistics emphasize the importance of accurate assessment and communication. Oncology nurses should complete a thorough history, review of systems and physical exam. Past medical history should include cancer diagnosis and all past and current medical conditions. Review of systems assessment should include all body systems as this can narrow the field of differential diagnoses. Focused nursing physical assessment should include vital signs, evaluation for orthostatic hypotension, assessment of fluid status measuring output, assessing for edema and monitoring daily weights , pain, manifestations of electrolyte imbalance malaise, fatigue, weakness, palpitations, paresthesias or muscle cramps and manifestations of metabolic alkalosis impaired mentation, hypotension or hypoventation.
Assessment for viral symptoms myalgias, arthralgias, rhinorrhea, headache, stiff neck, vertigo, tinnitus, chest pain, cough and fever as well as neurologic and vestibular symptoms must also be evaluated.
Metastatic brain lesions may cause increased intracranial pressure resulting in acute nausea, vomiting or headache. These symptoms coupled with change in motor or sensory function, personality change or seizures should be evaluated immediately. Recent advances in medications have increased the number of highly effective agents available to treat CINV. These agents work by binding to 5-HT3 receptors both in the peripheral and central nervous system, thus preventing the activation of the CTZ.
Currently fosaprepitant can be administered intravenously on day one of treatment followed by two additional days of oral therapy aprepitant or orally for 3 days. The mechanism by which corticosteroids decrease CINV has yet to be determined; however multiple clinical trials have demonstrated improved outcomes when corticosteroids are used in antiemetic regimens Musso et al. Adjunctive agents such as benzodiazepines and antihistamines may be helpful adjuncts to antiemetic therapy however Kris et al.
Benzodiazepines may be beneficial in patients experiencing anticipatory nausea. Benzodiazepines can be taken orally prior to chemotherapy treatment to reduce anticipatory nausea.
The activation or inhibition of these neurotransmitters forms the basis of pharmacologic therapy for CINV. Because multiple neurotransmitters are involved in this process, multiple antiemetic medications are necessary for the maximal prevention and treatment of CINV. The primary determinant of the prevalence of CINV is the inherent emetogenicity of the chemotherapy agents administered.
The emetogenicity of chemotherapy agents has been classified into 4 categories. Table 1 lists the emetogenicity of various chemotherapy agents given by injection. The characteristics of CINV seen with oral chemotherapy agents are different with regard to onset, duration, and severity. Table 2 lists the emetogenic level seen with oral chemotherapy agents.
In addition to the emetogenicity, other chemotherapy- related risk factors include high doses, fast infusions, and multiday chemotherapy administration. Because most chemotherapy regimens use more than 1 antineoplastic agent given on a single day, it is difficult to predict the emetogenicity of these combination regimens.
It is recommended that the antiemetic regimen be designed to be consistent with the highest emetogenicity associated with the chemotherapy agents given on each day. The 5-HT3 receptor antagonists are effective anti - emetic agents associated with minimal adverse effects. These agents block serotonin release from the gastrointestinal tract in addition to blocking serotonin receptors in the CNS.
When initially approved in the early s, the 5-HT3 antagonists became the first highly active antiemetics that did not have substantial adverse effects. The 4 agents in this class—dolasetron, granisetron, ondansetron, and the most recently approved palonosetron—are available in a variety of dosage forms in adults Table 3.
The 5-HT3 antagonists are more potent as antiemetic agents than antinausea medications. These agents demonstrate a plateau effect: For patients who can take oral medications, oral therapy is as effective as intravenous IV dosing. The 5-HT3 antagonists are well tolerated and have few adverse effects. The most often reported side effects include headache, constipation, and diarrhea.
It is unclear what the true incidence of adverse events is for the different 5-HT3 antagonists, because these are likely underreported. The FDA has added warnings to the label of ondansetron against the use of the drug by patients with a long QT syndrome and is recommending electrocardiographic monitoring for patients at high risk for this event—those with electrolyte abnormalities, congestive heart failure, or bradyarrhythmias, and patients using concomitant medications that can increase the QTc interval.
For patients without underlying cardiac rhythm disorders or concurrent treatment with other medications that prolong the QTc interval, it is not clear how clinically significant this potential adverse effect is.
It is generally accepted that there are no substantial differences in antiemetic efficacy among the 5-HT3 antagonists, except for palonosetron. Since then, several studies have provided information that further delineates the effects of palonosetron.
Corticosteroids Corticosteroids, and dexamethasone in particular, have long been used for the prevention and treatment of CINV. Despite the widespread use of corticosteroids, their precise antiemetic mechanism of action is still unclear. The potential mechanisms may include activation of glucocorticoid receptors in the CNS, decreased release of serotonin, inhibition of prostaglandin synthesis in the cerebral cortex, and alteration of cortical input into the emetic center in the CNS.
Dexamethasone is active in the acute and the delayed phases of CINV. The short-term use of dexamethasone in doses used in CINV is usually well tolerated, although the drug is sometimes underutilized, because of concern for its associated adverse effects. Hyperglycemia is often seen in patients with preexisting or undiagnosed diabetes. In some patients, the hyperglycemic effect is significant enough to warrant additional glucose monitoring or alterations of antidiabetic medications.
The appropriate dexamethasone dose depends on the emetogenicity of the chemotherapy and on whether an NK1 antagonist is coadministered. One group of researchers explored the dose—response relationship of dexamethasone in the context of highly emetogenic chemotherapy, showing that the mg and mg doses of the drug were associated with a higher complete response rate than the 4-mg and 8-mg doses.
The dose and schedule of dexamethasone should be modified if a patient will also receive an NK1 antagonist. Aprepitant and fosaprepitant inhibit the cytochrome CY P 3A4—based metabolism of dexamethasone and result in an approximately 2-fold increase in the area under the curve AUC of dexamethasone. Overall, dexamethasone doses are reduced by half if used concurrently with aprepitant. Available CINV guidelines differ slightly in their recommendations for dexamethasone dose.
For regimens with a high risk of delayed CINV, oral dexamethasone 8 mg daily or twice daily for 2 to 3 days is recommended, depending on whether an NK1 antagonist is also given.
All patients in the 2 studies combined received IV palonosetron 0.
Alternative Methods to Treat Nausea and Vomiting from Cancer Chemotherapy
Some people experience CINV within the first few hours of receiving Sometimes, the sights, sounds or smells of the treatment room can trigger this reaction. For this reason, most patients are usually given medication to avoid or prevent such serious side effects before undergoing emetogenic chemotherapy. The FDA has approved intravenous (IV) rolapitant (Varubi) for use in combination with other antiemetic agents to treat delayed.