Nausea And Vomiting - Copy.pdf

Radiation and Chemotherapy Induced Nausea and Vomiting Definition , Pathophysiology , And Treatment therapeutic antibodies ? Effect of CINV on QoL When CINV goes untreated, it affects upwards of 60% to 80% of patients with cancer. CINV negati...

Radiation and Chemotherapy Induced Nausea and Vomiting Definition , Pathophysiology , And Treatment therapeutic antibodies ? Effect of CINV on QoL When CINV goes untreated, it affects upwards of 60% to 80% of patients with cancer. CINV negatively impacts the quality of life (QOL) of the patient, and the QOL of the patient’s family. Without prevention and control of CINV, patients may experience many undesirable events that can affect their QOL and/or treatment outcomes, including discontinuation of chemotherapy. Other effects include lost workdays, reduced self-care, reduced ability to care for others and reduced ability to eat, unintended weight loss.  Nausea is described as an awareness of discomfort that may or may not precede vomiting; nausea is accompanied by decreased gastric tone and decreased peristalsis. Retching is the labored movement of Important abdomi nal and thoraci c muscl es Definitions associated with vomiting without the expulsion of vomitus. Vom i t i ng (em esi s) i s t he eject i on or expulsion of gastric contents through the m o u t h.
 Acut e onset : Occurs 0–24 hours aft er chemotherapy administration and commonly resolves within 24 hours (the ac ut e p hase b eg ins 1 to 2 hours aft er intravenous (IV) administration, intensity peaks after 5–6 hours)
Delayed onset: Occurs more than 24 Vomiting hours after chemotherapy administration and may peak 2 to 3 days post Onset

administration, can last up to 5 days. (Risk Factors ?) T he distinc tion b etween ac ute and delayed symptoms with respect to time of onset is somewhat arbitrary, and it becomes blurred when chemotherapy is administered for several consecutive days.  Anticipatory vomiting (or nausea) is triggered by sights, smells, or sounds and is a conditioned response; it is more likely to occur in patients whose previous post-chemotherapy nausea and vomiting was not well controlled. The onset can occur before or during administration of chemotherapy.
Vomiting Breakthrough emesis oc c urs d espite prophylactic treatment and necessitates Onset

additional rescue medications. Refractory emesis is emesis that occurs during treatment cycles when antiemetic prophylaxis or rescue therapy has failed in previous cycles. Progressive Muscle Relaxation Risk factors for CINV  Patient’s age History of nausea or History of motion (younger than 50 vomiting during sickness years) pregnancy 1. Patient- Poor control of History of chronic related risk nausea or vomiting in previous alcoholism (positive risk factor - Female sex factors :- chemotherapy cycles decreases incidence of emesis) Anxiety/high pretreatment expectation of nausea  The Drug type emetogenicity of the regimen used depend 1. Emetogenicity of on :- Drug dosage: Some drugs chemotherapeuti in lower dose are much c agents less of a problem than higher dose. Route of administration Schedule of administration


 C u r r e n t c l a s s i f ic a t i o n o f c h e m o t h e ra p i e s e m e t o g e n i c i t y includes four levels for intravenous 2. Emetogenici chemotherapy and two levels for oral c h e m o t h e r a p y.
ty of chemothera peutics  Emetogenicity 1. Emetogenicity: percentage of patients who will experience acute emesis if not treated. 2. In I.V: High = greater than 90% Moderate = 30% to 90% Low = 10% to less than 30% Minimal (rare) = less than 10% Emetogenic Potential of Intravenous Chemotherapy Agents Emetogenic Potential of Intravenous Chemotherapy Agents Emetogenic Potential of Intravenous Chemotherapy Agents Emetogenic Potential of Intravenous Chemotherapy Agents Emetogenic Potential of Oral Chemotherapy Agents Levels for oral chemotherapy are moderate to high, and minimal to low. In general, the estimates of risk are based on the risk during an entire course of therapy, rather than after a single dose. Emetogenic Potential of Oral Chemotherapy Agents Emetogenic Potential of Oral Chemotherapy Agents Estimating the emetogenicity of chemotherapy combinations The primary literature of the regimen should always be consulted to
determine the emetic risk. Should that not be available, the antiemetic regimen should be geared toward the chemotherapy agent with the highest emetogenicity level given on that day. For example, in a chemotherapy combination with one high-risk

agent and one with a moderate risk, the antiemetic regimen should be appropriate for the high-risk chemotherapy agent. Pathophysiology of Vomiting Pathophysiology Of CINV: Role of CTZ In the CNS, the CTZ; it lies outside the blood–brain barrier. When the CTZ senses toxins and noxious substances in the blood or cerebrospinal fluid, it triggers The emetic response by releasing neurotransmitters that travel to the VC. Pathophysiology Of CINV: Role of GTI The GI system also plays a large part in the initiation of the emetic response. The GI tract contains enterochromaffin cells in the GI mucosa. When these cells are damaged by chemotherapy, radiation, or mechanical irritation, serotonin/substance P is released, which can stimulate the vagal afferents as well as directly stimulate the VC. The VC then initiates the emetic response. Pathophysiology Of CINV: Brain The cerebral cortex can stimulate the emetic center in response to emotional states, such as anxiety, pain, and conditioned responses (anticipatory nausea and vomiting).  Variety of receptors are involved in these centers, including Histaminergic (H1), Receptors Cholinergic (muscarinic Involved in the M1), Pathophysiolo Dopaminergic gy of Vomiting (D2) Serotonergic (5HT3) Neurokinin-1 (NK1) receptors.
 Complex interactions between central and peripheral pathways occur in the production of the clinical features of nausea and vomiting. The most important areas involved peripherally Pathophysiolo are the gastric mucosa and smooth muscle (the gy of Vomiting enteric brain) and the afferent pathways of the vagus and sympathetic nerves. Centrally, the signif icant areas involved are the chemoreceptor trigger zone (CTZ), and the v o m i t i n g c e n t e r
 Serotonin plays an important role in the genesis of acute vomiting, occurring within the f irst 2 4 ho urs o f c he m o the rap y, because Anticancer drugs can stimulate a release of serotonin from Enterochromaffin Pathophysiolo cells in the GI tract due to cell damage. gy Of Acute Nausea And Serotonin then activates the emetic Vomiting response by binding to 5HT-3 receptors located on the afferent vagal nerves in the intestinal wall , which projects to the CTZ and vomiting center stimulating the vomiting center.
 Substance P can also be released from enterochromaffin cells in the GI tract playing an axillary role in the delayed induction of nausea Pathophysiolo and vomiting. gy Of Delayed Nausea And Substance P released in response Vomiting to chemotherapy and binds to (NK1) receptors in the CTZ and vomiting center thereby mediating the induction of vomiting. Pathophysiology Of Radiation Nausea And Vomiting The pathophysiology of RINV likely involves several mechanisms. If the gastrointestinal tract is included in the field of radiation, direct effects are likely with stimulation of afferent pathways in the upper gastrointestinal tract. In addition, it is theorized that the chemoreceptor trigger zone in the area postrema may also be involved, possibly from radiation- induced tissue breakdown products.
 3. Radiation therapy The incidence and severity of radiation-induced nausea and vomiting vary by site of radiation and size of radiation field :- Minimal risk: Extremities, breast Mildly emetogenic: head and neck, thorax region, pelvis Moderately emetogenic: upper abdomen, Cranium, craniospinal. Highly emetogenic: Total body irradiation, total nodal irradiation. Radiation therapy  Effect of CINV on QoL Definitions Check point /Questions Prognostic Factors For CINV Pathophysiology Of CINV General Principles for Managing CINV and Radiation-Induced Nausea and Vomiting Determining The Culprit Because nausea and vomiting are common symptoms among patients with cancer, causes other than chemotherapy should also be considered. Among the diverse causes of nausea and vomiting in patients with cancer are intestinal obstruction, liver metastases, central nervous system involvement (brain metastases), and other medications (particularly narcotic analgesics). These conditions should be considered in the etiology, especially when the time course or duration of nausea and vomiting is unusual for the known chemotherapy- induced syndromes.  Prevention is the key. Prophylactic antiemetics should be administered before moderately or highly emetogenic agents and before moderately and highly emetogenic radiation. Prevention Rescue antiemetics should be available if acute symptoms or ineffective antiemetic prophylaxis occurs
 Patients need to be protected throughout the full period of risk for nausea/vomiting: 3 days for highly emetogenic Duration of regimens. protection 2 days for moderately emetogenic regimens.  For multidrug regimens, determine the emetogenic risk and the antiemetic combination according to the drug with the highest emetic risk in the regimen. Appropriat e Antiemet ic Regimen The most common antiemetic regimen for highly emetogenic chemotherapy and radiation is the combination of a neurokinin 1 (NK1) receptor antagonist, a serotonin receptor antagonist, antagonist and dexamethasone/ Olanzapine may be patients

added in some patients.  Appropriate Antiemetic Regimen For moderately emetogenic chemotherapy, the most common antiemetic regimen now includes a serotonin receptor antagonist and dexamethasone. Addition of an NK1 receptor antagonist may be considered after risk stratification. Single-agent phenothiazine, or steroids are used for low emetogenic regimens). Equivalent efficacy can be achieved with IV, subcutaneous, or oral administration of the appropriate agents. Selection of the route of administration should be based on other considerations (e.g., patient convenience, insurance coverage, organizational contract) I.V chemotherapy I.V chemotherapy I.V chemotherapy Emesis Prevention Algorithm for Oral Chemotherapy Emesis Prevention Algorithm for Oral Chemotherapy Radiation-Induced Nausea and Vomiting High-risk RT: : 5-HT3 RA + DEX. Moderate-risk RT: 5-HT3 RA. Low-risk RT : DEX , DOP RA, or 5-HT3 RA as either prophylaxis or rescue Minimal-risk RT: Rescue with DEX, DOP RA, or 5-HT3 RA  NCCN guidelines advise that the general principle of breakthrough treatment is to add one agent from a different class than in the patient's current regimen. Any of the following may be selected :  Olanzapine Treatment of  DEX Breakthrough  5-HT3 RA Emesis  Lorazepam  Metoclopramide  Phenothiazine (eg, promethazine, prochlorperazine)  Cannabinoid (eg, dronabinol, nabilone): are generally used after other regimens have failed  Scopolamine transdermal  Consider using a H2 blocker or proton pump inhibitor for dyspepsia (which can mimic nausea). Potential drug interactions between antineoplastic agents or antiemetics and Other other drugs should always be considered. Consideration Follow-up is essential. The response to s the emetogenic regimen should always guide the choice of antiemetic regimen for subsequent therapy courses. Cannabinoids are generally used after other regimens have failed.