Nusea and vomiting supportive ppt
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This document discusses chemotherapy-induced nausea and vomiting (CINV) management. It begins by outlining the magnitude of CINV as a problem for patients and its impact on quality of life. It then defines the different types of CINV and classifies chemotherapeutic agents based on their emetic risk. The pathophysiology of CINV is described as involving several areas of the brain and neurotransmitters like serotonin, dopamine, acetylcholine, and histamine. Guidelines for assessing, classifying severity of, and treating CINV are provided, focusing on the main classes of antiemetics - 5HT3 antagonists, dopamine antagonists, and NK1 receptor antagonists.
![Treatment-induced nausea and vomiting is the
most important cause
• Chemotherapy: usually within 5 days following treatment
• Analgesics (e.g. opioids)
• Radiotherapy (especially when upper gastrointestinal [GI] tract or
mediastinum is involved in the radiation field)
- Selective serotonin reuptake inhibitors (many cancer patients develop
depression )
- Postoperative nausea and vomiting (after general anaesthesia)](https://image.slidesharecdn.com/nuseaandvomitingsupportiveppt-200807205640/85/Nusea-and-vomiting-supportive-ppt-11-320.jpg)
Nusea and vomiting supportive ppt
- 1. CINV (chemo therapy induced nusea and vomiting ) management presented by : Heba bakri Ass. Lecturer clin.onc.dep. AUH
- 2. Agenda : • magnitude of the problem • Definition , Types of CINV and AE • Classification of ematogenic agents • Pathophysiology and Risk factors • Classification of anti emetics • management ( assessment - treatment – general guidelines ) • Asco and NCCN guidelines
- 3. Magnitude of the problem - N& V are two of the greatest fears of patients with cancer. - May be a result of the disease status of the patient but are more frequently associated with anti-cancer treatment. - They are distressing symptoms have a considerable impact on all aspects of the patients’ quality of life , their family and caregivers which lead to escalate over time, and potentially lead to changes in or delay of the chemotherapy regimen, or even patient’s refusal to continue
- 4. If Inadequately controlled can precipitate a number of medical complications that may prove life-threatening, including dehydration, electrolyte imbalance and malnutrition, or cause physical damage, including Mallory–Weiss rupture of the oesophagus.
- 5. Nausea should be clearly distinguished from vomiting !!!!! •Nausea refers to the gastric and/or medullary distress with distaste for food and an urge to vomit, but without necessarily encompassing vomiting. It should be emphasised that a patient who is not vomiting may still experience severe nausea that needs to be comprehensively diagnosed and managed .
- 6. 4Types of nausea and vomiting : AssociationPersistanceTime Early : 12 h after CTH Late : > 12 to 24h after CTH Acute following the administration of platinum analogues, alkylating agents or anthracyclines. persist for 6–7 days .more than 24–48 hoursChronic linked to visual, gustatory, olfactory and environmental factors associated with previously administered chemotherapy (the “white uniform” syndrome before, during or after the administration of a subsequent course of treatment if previous emetic control has been inadequate Anticipatory
- 7. 4- Breakthrough nausea and vomiting : • Occur despite prophylactic treatment and are usually abrupt, sudden and acute. • The specific reasons for it inadequately understood • often in young patients, and/or women, and/or with history of motion illness) • but they represent a medical emergency that needs to be timely diagnosed and treated.
- 8. Aetiology: • a) Treatment-induced • b) metabolic Causes • c) Gastrointestinal Causes • d) Neurological Disorders • e) others
- 9. *** metabolic Causes - Hypercalcaemia - Renal failure (uraemia) - Adrenocortical failure - Hypo-or hyperglycaemia *** Gastrointestinal Causes - Liver metastases or hepatitis - Biliary duct obstruction - Pancreatic disorders - Acute abdomen/peritonitis - Functional bowel disease (reduced bowel motility, paralytic ileus) - Obstructive bowel disease (peritoneal carcinomatosis, colorectal cancer) - Gastric or oesophageal cancer -Gastritis, gastro-oesophageal reflux disease, ulcus, pyloric stenosis
- 10. *** Neurological Disorders - Brain metastases with high intracranial pressure - Medullary or cerebellar dysfunction - Carcinomatous or infectious meningitis - Cerebral hemorrhage *** Others Myocardial infarction, viral infections, hypertension crisis
- 11. Treatment-induced nausea and vomiting is the most important cause • Chemotherapy: usually within 5 days following treatment • Analgesics (e.g. opioids) • Radiotherapy (especially when upper gastrointestinal [GI] tract or mediastinum is involved in the radiation field) - Selective serotonin reuptake inhibitors (many cancer patients develop depression ) - Postoperative nausea and vomiting (after general anaesthesia)
- 12. Classification of CTH agents acc.to ematogenic risk : • Highly emetic • Moderately emetic • Low emetic • Minimal risk of emesis
- 15. Pathophysiology Vomiting center (VC ) receives input from GI mucosa, Chemoreceptor trigger zone(CTZ), and vestibular apparatus , Efferents fibers from this center when stimulated , cause stimulation of phrenic nerve supplying to diaphragm and of somatic nerve supplying the abdominal muscles to promote emesis
- 16. • Irritation of GI mucosa by drugs or irritants leads to release of serotonin that stimulates VC via 5HT3 receptors • CTZ is rich in D2 receptor (release of dopamine ) and 5HT3 (release of serotonin ) and neurokinin (NK1) receptor • stimulation of vestibular apparatus and cerebellum, these structures result in stimulation of VC by activating M1 (release of acetylcholamine ) & H1 receptors( realease histamine )
- 18. • Neurotransmitters Involved : - Histamine via H1 receptors - Serotonin via 5HT3 receptor - Acetylcholine via M receptors - Dopamine via D2 receptors
- 21. Risk factors • Younger age • Female gender • Tumour burden • Rate, route and dosage of chemotherapy administration • Emetogenic potential of chemotherapy agent • Anxiety or depression
- 22. D.D ???? • Obstructive Bowel Disease : - In cancer patients, bowel obstruction is often a reason for nausea and vomiting , the obstruction can occur at any level distal to the duodenum. Usually, treatment starts conservatively over a period of 2–5 days by (nasogastric tube, adequate intravenous fluid supplementation, diuresis monitoring). • If no improvement occurs within 72 hours, surgery should be considered. In malignant large bowel obstruction, endoscopically placed, self expanding metal stents may be used as palliation.
- 23. Assessment • 1- questions • 2- grading • 3- investigations
- 24. a) Questions : • what is Primary cancer diagnosis? • what is cancer treatment ? • When was the last treatment / tablet taken? • History of onset, duration, frequency, volume. • Review use of anti-emetics and other medications. • Any abdominal pain? Review dietary intake over last few days • N.B : If the patient is on oral anticancer therapy that is associated with nausea and vomiting and the patient has moderate or severe symptoms, the anticancer therapy must not be continued until it has been discussed with the treating oncology medical team or the on-call oncologist
- 25. Grading of N&v : 1-2 episode / dayGrade 1Mild 3-5 episodes / dayGrade 2Moderate > 6 episode /day >10 episode /day *** requires urgent intervention can be life thretening Grade 3 Gadre 4 Severe
- 26. c) Investigation 1- Clinical examination • Abdomen, neurological examination, blood pressure, diuresis. 2- Blood examination • Liver tests, renal function , electrolytes , blood gas. 3- Imaging modalities • Ultrasonography, abdominal X-ray. • If clinical examination suggests neurological disorder: CT or MRI , lumbar puncture if carcinomatous or infectious meningitis is suspected • If clinical examination suggests abdominal cause: Gastrografin meal, abdominal CT scan • Endoscopic examination (gastro-oesophagoscopy, colonoscopy) whenever clinically indicated
- 28. 1- Serotonin 5HT3 Antagonist : • Drugs Available and dose per day : 1st generation of 5HT3antagonists : 1- Ondansetron (ZOFRAN ) (ONDALENZ ) 32 mg / day (Ondansetron 8 mg iv slow over 15 mins , ½ hr before chemotherapy , 2 doses 4 hr apart ) . 2- Granisetron (GRANISET) (GRANYTRIL) (EMEX) 10 mg / kg / day (1-3 mg diluted in 20-50 ml saline infused iv over 5 mins before chemotherapy, repeat after 12 hrs ) 3- Dolasetron 1.8 mg / kg / day
- 29. • 2nd generation of 5HT3antagonists : Palonosetron (ALOXI) 250µg • by slow iv inj 30 min before chemo • longest acting 5HT3 receptor blocker with highest affinity for 5HT3 receptor (t1/2=40 hrs) APF530 250-mg (sub cut. Granisetrone ) subcutaneous dose is equivalent to granisetron at 5 mg IV, and the 500- mg dose is equivalent to granisetron at 10 mg IV. APF530 is non inferior to IV palonosetron in preventing acute CINV after MEC or HEC.
- 30. • Mechanism of Action :
- 31. • Pharmacological criteria : - Potent anti emetics - Excellent safety profile - Ondansetron- prototype - the antiemetic action is restricted to emesis caused by vagal stimulation. - High first pass metabolism - Excreted by liver & kidney - No dose reduction in renal insufficiency but needed in hepatic insufficiency - orally or intravenously.
- 32. • Indications 1- Chemotherapy induced nausea & vomiting – given 30 min. before chemotherapy. 2- Postoperative & post radiation nausea & vomiting • Adverse Effects 1- Headache & constipation 2- All three drugs cause prolongation of QT interval, but more pronounced with dolasetron 3- Palonosetron ( ALOXI ) :- - Rapid i.v. injection causes blurring of vision
- 34. 2-Dopamine D2 Antagonists • Drugs available - Metoclopramide(PRIMBERAN ) : 2.5 mg b.d , ORAL OR iv , cross BBB - Domperidone (motilium ) 10 mg b.d ORAL ONLY , don’t cross BBB
- 35. Mechanism of action : 1- act on CTZ which is outside BBB both have antiemetic effects. But as metoclopramide crosses BBB it has adverse effects like extrapyramidal side effects but Domperidone is well tolerated 2- Both drugs are also prokinetic agents due to their 5 HT4 agonist activity. Indication : - Antiemetic- ( Postoperative, drug induced, radiation , disease associated ( migraine) - Gastro kinetic- to accelerate gastric emptying, GERD
- 36. Adverse effects of Metoclopramide Sedation, Dizziness, loose stools, muscle dystonias, Long term parkinsonism, galactorrhoea, gynaecomastia Adverse effects of domperidone : - Low ceiling antiemetic and prokinetic , Less Efficacious gastrokinetic, not useful in highly emetogenic chemotherapy - Side effects- Less as compared to Metoclopramide ( Dry mouth, loose stools, headache, rashes, galactorrhoea are mild )
- 38. 1- Aprepitant :- ( emend oral) Dose- 125 mg+ 80 mg+ 80mg for 3 days Aprepitant- Cisplatin induced vomiting Combined with IV Ondansetron and Dexamethason - Metabolism Well absorbed orally and penetrates BBB ,Metabolised in liver by CYP3A4 2- Fosaprepitant ( emend IV) : -Well tolerated - Avoid combination with cisapride-QT prolongation
- 40. • Indication : aprepitant : For patient undergoing multiple cycles of chemotherapy Fosapritant : PONV (preoperative nusea and vomiting ), adjuvant in CINV adverse events : Weakness, fatigue, flatulence, rise in liver enzymes
- 43. • Lorazepam is an adjunctive drug but not recommended as a single agent • diphenhydramine is no longer accepted as an adjunctive drug for emesis prophylaxis. • Trials with cannabinoids are old and no comparison with contemporary antiemetics is found. • medical marijuana use or complementary/alternative therapies (such as ginger, acupuncture, acupressure etc.) remains insufficient for a recommendation regarding for the prevention of treatment related N&V in patients with cancer.
- 46. • The systematic review of literature which focused only on randomised controlled trials (RCTs) and systematic reviews between November 1, 2009 and June 1, 2016. • The review process yielded 41 publications (35 RCTs and 6 meta- analyses), majority about prevention of chemotherapy-related N&V, and less publications about radiation-induced N&V and for paediatric patients found.
- 48. - addition of olanzapine (10 mg/day, po, D1-4), which is an antipsychotic drug that blocks multiple neurotransmitters in central nervous system, to standard of care (SOC; NK1 antagonist + dexamethasone 12 mg on D1 and 8 mg D2-4 + 5HT3 antagonist) was tested in patients treated with high-emetogenic risk chemotherapy. showed the superiority no nausea during the overall assessment period (0–120 h) and complete response (no emetic episodes and no rescue medication), respectively. -ASCO panel revealed the new SOC antiemetic regimen that should be used for high-emetogenic risk drugs as a 4-drug combination (NK1 antagonist + 5HT3 antagonist + dexamethasone + olanzapine). To note, for antracycline and cyclophosphamide regimen dexa is recommended only for the first day, if a 4-drug antiemetic combo will be used as aprepiant affect metabolism of dexa High-emetic risk, single-day chemo: -another NK1 antagonist, rolapitant which was formerly approved by FDA in 2015, listed among the options that could be used in the treatment of CINV. Also, non-inferiority of subcutaneous extended release granisetron to i.v. palonosetron and superiority to ondansetron were shown in different trials.
- 49. 1- receiving carboplatin with a dose AUC ≥4 are accepted at the higher end in terms of emesis risk in this category. Studies of both rolapitant and aprepitant showed superior emesis prophylaxis in these patients with regard to 5HT3 + dexa combination. Moderate-emetic risk, single-day chemo: Recommendations regarding moderate-emetogenic regimens could be reviewed in 3 parts. 2- the majority of moderate-emetogenic regimens a combination of 5HT3 + dexa on D1 only would be enough. However, if the patient will receive an agent that is known to cause delayed emesis (like cyclophosphamide, oxaliplatin or doxorubicin) dexa may be offered for D2- 3, 3- palonosetron is no longer the agent of choice for moderate-emetogenic risk drugs owing to lack of convincing data, thus any 5HT3 antagonist is acceptable for this risk group.
- 50. • Low-emetic risk, single-day chemo: Since the quality of evidence about antiemetic prophylaxis is low for this stratum, the guideline proposed single 5HT3 antagonist or single dose 8 mg dexamethasone with an informal consensus and moderate strength of evidence. • Minimal-emetic risk, single-day chemo: As previous, these patients should not be offered routine antiemetic prophylaxis, unless foreseen such a need by the treating physician.
- 51. • recommendations about the antiemetic approach for radiation therapy (RT) in this update. 1- For high (risk > 90%, total body irradiation) and moderate risk (30–90%, craniopsinal, upper abdomen RT) radiation therapies: prophylactic approach with 5HT3 plus dexamethasone is recommended. 2- Whereas for low (risk 10–30%, brain, head&neck, thorax, pelvis) or minimal risk (<10%, extremity, breast) RT : a rescue strategy is recommended primarily with 5HT3, dexamethasone or dopamine antagonist. The emetic risk of anti-neoplastic agent should guide the antiemetic prophylaxis in patients receiving chemoradiotherapy unless the risk related with RT is higher.
- 52. Treatment of CINV : • If moderate vomiting, without complications Outpatient management 1- treatment with serotonin antagonist orally (or intrarectally) and/or metoclopramide and/or corticosteroids 2- Avoid drugs that reduce bowel motility (e.g. loperamide, hyoscyamine, anticholinergic agents) 3- Check the evolution after 24 hours
- 53. • If severe or in case of complications Consider hospitalisation 1- Serotonin antagonists: e.g. a) granisetron: (granytril ) 3 mg × 1–3/day intravenously (i.v.) or b) ondansetron: (Zofran ) 8 mg × 1–3/day i.v. over at least 10 minutes, and at regular intervals thereafter (“round the clock” administration). • In case of resistance: continuous i.v. perfusion of chlorpromazine 25 mg/day, or olanzapine 5–20 mg/day
- 54. General principles in management of multiday ematogenic chemotherapy regimen
- 63. • N& V are two of the greatest fears of patients with cancer. • If Inadequately controlled can precipitate a number of medical complications that may prove life-threatening, • 4 types ( acute (<12 h) – chronic (12-24 h) – anticipatory – break through ) • AE (Treatment-induced , metabolic , Gastrointestinal , Neurological , others ) • Classification of eamtogenicity of CTH agents (Highly emetic , Moderately emetic , low emetic , Minimal risk of emesis ) • Grading of N&v : mild (grade 1 ) (1-2 episode /day ) , moderate (grade 2) ( 3- 5 episode ) , severe (grade 3) (>6 ) (garde 4 ) ( > 10 ) episode . • Classification of antiemetics ( 5HT3 antagonists , serotonin antagonists , NK1 RA )