Corticosteroids Classes of Antiemetics
10.2.4.3 5-HT
3 Receptor Antagonists Four serotonin receptor antagonists—ondanse- tron, granisetron, dolasetron and palonosetron— are available in the United States. Tropisetron is only available internationally and has not yet been approved by the Federal Drug Administration FDA. When fi rst approved in the early 1990s, these agents revolutionized the antiemetic prophy- laxis of highly and moderately emetogenic che- motherapy, largely replacing phenothiazines and benzamides as fi rst-line therapy due to superior effi cacy and signifi cantly fewer side effects Grunberg et al. 2010 . 5-HT 3 receptor antagonists are thought to prevent CINV by inhibiting sero- tonin, which is released from enterochromaffi n cells in the gastrointestinal mucosa, from initiating afferent transmission to the CNS via vagal and spi- nal sympathetic nerves Jordan et al. 2007 . They may also work by blocking serotonin stimulation at the CTZ and other CNS structures. Prior to 2003, there were three FDA- approved 5-HT 3 receptor antagonists: ondansetron, granisetron and dolasetron. Numerous clinical trials demonstrated their clinical equivalence and showed there was no signifi cant difference whether given orally or intravenously Corapcioglu and Sarper 2005 ; Dupuis et al. 2013 . Ondansetron Ondansetron is highly effective in controlling acute emesis induced by moderately and highly emetogenic chemotherapy in pediatric oncology patients Carden et al. 1990 ; Hewitt et al. 1993 . Used alone, ondansetron is superior to combina- tion therapy with metoclopramide and dexameth- asone or chlorpromazine and dexamethasone and is free of extrapyramidal and sedative side effects Dick et al. 1995 ; Jimenez et al. 1997 ; Koseoglu et al. 1998 . Ondansetron used in combination with corticosteroids has been shown superior to ondansetron monotherapy in control of CINV with highly emetogenic chemotherapy in pediat- ric cancer patients Alvarez et al. 1995 ; Roila et al. 1998 . Alvarez et al. 1995 conducted a small but signifi cant double-blind, placebo- controlled, randomized crossover trial comparing ondansetron and dexamethasone to ondansetron and placebo in 25 children 3–8 years of age receiving highly emetogenic chemotherapy for solid tumors. Complete emetic control was achieved in 61 receiving both ondansetron and dexamethasone versus 23 in those treated with ondansetron alone p = 0.04. The lowest fully effective dose of ondanse- tron is 0.45 mgkgday, with a single daily dose schedule no less effi cacious than a multiply divided dose schedule Sandoval et al. 1999 . Oral and intravenous IV drug administration has also been found statistically equivalent White et al. 2000 . White et al. 2000 con- ducted a double-blind, parallel-group, multi- center study comparing the effi cacy and safety of IV and liquid ondansetron both arms with oral dexamethasone in the prevention of CINV in pediatric patients receiving moderately to highly emetogenic chemotherapy. Complete control of emesis was achieved in 89 of patients in the IV group and 88 of patients in the oral syrup group during the worst day of chemotherapy treatment and was well tolerated in both arms White et al. 2000 . For highly emetogenic che- motherapy, the recommended dose of ondanse- tron is 0.15 mgkg 30 min prior to initiation of chemotherapy and repeated q8 h, although other regimens such as 0.45 mgkg as a single daily dose have been shown equally effective Dupuis et al. 2013 . When giving multiple-daily dosing, ondansetron can potentially be spaced to q12 h for moderately emetogenic chemotherapy Dupuis et al. 2013 . A single-center retrospec- tive chart review has reported ondansetron-load- ing doses of 16 mgm 2 maximum, 24 mg IV, followed by two doses of 5 mgm 2 q8 h, to be safe in infants, children and adolescents Hasler et al. 2008 . Currently, the oral and injectable ondansetron formulations are approved for use without dosage modifi cation in patients 4 years, including patients with renal insuffi ciency. Ondansetron clearance is diminished in patients with severe hepatic insuffi ciency; therefore, such patients should receive a single injectable or oral dose ≤8 mg. The major adverse effects include: head- ache, constipation or diarrhea, fatigue, dry mouth and electrocardiographic ECG abnormalities including QTc prolongation Culy et al. 2001 . Buyukavci et al. 2005 monitored ECGs in 22 children with acute lymphoblastic leukemia ran- domized to receive a single dose of either ondan- setron 0.1 mgkg or granisetron 40 mcgkg. The granisetron group demonstrated a signifi cant decrease in mean heart rate at 1 and 3 h post dos- ing and a signifi cant QTc prolongation at 1 h post dosing although all values eventually returned to baseline; no signifi cant changes were seen in the ondansetron group Buyukavci et al. 2005 . Pinarli et al. 2006 randomized 38 children to either ondansetron or granisetron, and patients were monitored with a 24-h ECG post antiemetic administration. Compared to baseline, patients who received granisetron but not ondansetron demonstrated a signifi cant prolongation of the QTc interval and shortening of the PR interval and QRS complex, though none of these abnor- malities were clinically signifi cant Pinarli et al. 2006 . Granisetron Granisetron has demonstrated effi cacy in pre- venting and controlling CINV due to moderately to highly emetogenic chemotherapy in children and when used alone is superior to combination therapy using metoclopramide and prometha- zine, metoclopramide and dexamethasone, and chlorpromazine and dexamethasone Hählen et al. 1995 ; Komada et al. 1999 . In a small study, Hirota et al. 1993 showed no signifi cant differ- ence between the combination of granisetron and methylprednisolone compared with granisetron alone in pediatric oncology patients. Effective granisetron doses in children range from 20 to 40 mcgkgday, often administered IV once daily prior to chemotherapy or orally q12 h Dupuis et al. 2011 . In the United States, granisetron injection, transdermal patch, and oral tablets are approved for initial and repeat prophylaxis in patients receiving emetogenic chemotherapy, including high-dose cisplatin. Granisetron is pharmacologically and pharmacokinetically dis- tinct from ondansetron; however, clinically it appears equally effi cacious and safe Gebbia et al. 1994 . Current pediatric guidelines recom- mend granisetron at 40 mcgkg IV as a single daily dose for moderately to highly emetogenic chemotherapy or 40 mcgkgdose PO q12 h for prevention of CINV from moderately emetogenic chemotherapy Dupuis et al. 2013 .Parts
» Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Introduction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» History and Physical Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Defi ning the Risk for Serious
» Initial Laboratory Evaluation Diagnostic Evaluation
» Chest Radiography CXR A supine CXR may identify pleural effusions,
» Computed Tomography CT Radiographic Imaging
» Magnetic Resonance Imaging MRI
» Positron Emission Tomography PET
» Aspergillus Galactomannan GMN Biomarkers for Invasive
» 1,3-β- Biomarkers for Invasive
» Polymerase Chain Reaction PCR
» Viral Studies Diagnostic Evaluation
» Invasive Procedures: Diagnostic Evaluation
» Adult FN Guidelines Empiric Management
» Monotherapy Versus Combination Therapy
» Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
» Alterations in Initial Empiric FN Antibiotic Management
» Outpatient Management of FN Although there remains a lack of one uniform
» Choice of Empiric Antifungal Therapy
» Duration of Antimicrobial Empiric Management
» Endovascular Sources Empiric Management
» Adjunctive Treatment Empiric Management
» Emergence of Resistant Empiric Management
» Red Blood Cell Administration
» Granulocyte Transfusion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hemolytic Transfusion Risks of Blood Product
» Infection and Sepsis Risks of Blood Product
» Allergic Reactions Risks of Blood Product
» Febrile Nonhemolytic Risks of Blood Product
» Transfusion-Related Acute Risks of Blood Product
» Transfusion-Associated Risks of Blood Product
» Iron Overload Risks of Blood Product
» Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» General Management Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Alkalinization Urinary alkalinization has been a long-standing
» Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
» Rasburicase Rasburicase, recombinant urate oxidase, converts
» Renal Interventions Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pathophysiology Superior Vena Cava
» History and Physical Exam SVCSSMS should be suspected in a patient
» Imaging Studies The diagnosis of SVCSSMS is often made on
» Other Studies Tissue is required to make a defi nitive diagnosis
» Treatment Superior Vena Cava
» History and Physical Exam Small pericardial effusions are frequently asymp-
» Imaging and Other Studies The presence of a pericardial effusion can be
» History and Physical Exam Many patients with small pleural effusions are
» Imaging Studies When a pleural effusion is suspected, a chest
» History and Physical Exam Patients with pheochromocytoma typically have
» Laboratory Studies The diagnosis of pheochromocytoma is best made
» Imaging Studies Clinical Presentation
» Pulmonary Leukostasis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Presentation Spinal Cord Compression
» Differential Diagnosis Spinal Cord Compression
» Imaging MRI of the spine can help narrow the differential
» Surgery Surgery in spinal cord compression can be uti-
» Radiation Therapy The advantages of external beam radiation ther-
» Outcomes Spinal Cord Compression
» Presentation Altered Mental Status
» Initial Management Altered Mental Status
» Metabolic The metabolic causes of AMS or seizure in pedi-
» Chemotherapy-Associated Neurotoxicity Differential Diagnosis
» Posterior Reversible Encephalopathy Syndrome
» Outcomes Altered Mental Status
» Initial Management Increased Intracranial
» Soft Tissue A large meta-analysis of published data suggests
» Cerebrospinal Fluid Hydrocephalus is an excess of CSF within the
» Hemorrhage and Thrombosis Differential Diagnosis
» Idiopathic Intracranial Hypertension Differential Diagnosis
» Presentation of Stroke Cerebrovascular Disease
» Differential Diagnosis Cerebrovascular Disease
» Etiology of Stroke in Pediatric
» Ischemic Stroke After an ischemic stroke is diagnosed, the patient
» Hemorrhagic Stroke Hematomas can expand over several hours from
» Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Chronic Myelogenous Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hyperhydration Other Treatment Modalities
» Hydroxyurea Other Treatment Modalities
» Cranial Irradiation Other Treatment Modalities
» Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-
» Pseudohypoxemia Due to the rapid consumption of oxygen by leu-
» Pseudohypoglycemia Consumption of glucose by excess leukocytes
» Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-
» Transfusion Practice with Other Supportive Care
» Anesthetic Procedures Other Supportive Care
» Neutropenic Enterocolitis Gastrointestinal Infection
» Perirectal Abscess Gastrointestinal Infection
» Gastrointestinal Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pancreatitis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Bowel Obstruction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Abdominal Compartment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» ALL Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Other Malignancies Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Central Venous Catheters Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nociceptive Pain Types of Pain
» Neuropathic Pain Types of Pain
» World Health Organization Pharmacologic Treatment
» Intermittent Opioid Use Pharmacologic Treatment
» Long-Acting Opioids Pharmacologic Treatment
» Breakthrough Dosing Pharmacologic Treatment
» Opioid Rotation Pharmacologic Treatment
» Patient-Controlled Analgesia Pharmacologic Treatment
» Constipation Side Effects of Opioids
» Nausea and Vomiting Nausea and vomiting are rare opioid side effects
» Pruritus Pruritus is a common side effect of opioid use
» Sedation Side Effects of Opioids
» Confusion and Agitation Renal and hepatic function should be checked
» Respiratory Depression When dosed appropriately, opioids rarely result
» Myoclonus Patients receiving very high doses of opioids for
» Urinary Retention Urinary retention can be caused by any opioid but
» Calcium Channel Blockers Neuropathic Pain
» Serotonin and Norepinephrine Neuropathic Pain
» Tricyclic Antidepressants Neuropathic Pain
» Interventional Techniques Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vincristine-Related Peripheral Oncology-Specifi c Pain
» Osteonecrosis Oncology-Specifi c Pain
» Post-lumbar Puncture Oncology-Specifi c Pain
» Mucositis Pain Oncology-Specifi c Pain
» Pathophysiology of Emesis Chemotherapy-Induced
» Principles of Emesis Control in the Cancer Patient
» Emetogenicity of Chemotherapy Chemotherapy-Induced
» Dopamine Receptor Antagonists Classes of Antiemetics
» Corticosteroids Classes of Antiemetics
» Cannabinoids The plant Cannabis contains more than 60 differ-
» Other Antiemetic Agents Antihistamines
» Alternative Therapies Ginger Classes of Antiemetics
» Management of CINV Management of CINV Table
» Special Considerations Anticipatory Nausea and Vomiting
» Radiation-Induced Nausea Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Initiation The initiation stage occurs immediately following
» Primary Damage Response Pathophysiology of Oral Mucositis
» Signal Amplifi cation Pathophysiology of Oral Mucositis
» Ulceration Ulceration is the phase with the most clinical sig-
» Healing Pathophysiology of Oral Mucositis
» Clinical Course of Oral Mucositis
» Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Palifermin Prevention and Treatment
» Low-Level Laser Therapy Prevention and Treatment
» Glutamine Prevention and Treatment
» Cryotherapy Prevention and Treatment
» Oral Care Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Infections Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nutrition Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Dietary Counseling Nutrition Intervention
» Appetite Stimulants Nutrition Intervention
» Enteral Tube Feeding Nutrition Intervention
» Parenteral Nutrition Nutrition Intervention
» Nutrition and Survivorship Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Neutropenia Hematologic Toxicity
» Management of Thrombocytopenia Hematologic Toxicity
» Management of Anemia Hematologic Toxicity
» Somnolence Syndrome Central Nervous System
» Lhermitte’s Sign Central Nervous System
» Skin Complications Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Mucositis Head and Neck
» Ear Complications Head and Neck
» Laryngeal Complications Head and Neck
» Dysphagia and Esophagitis Gastrointestinal
» Nausea, Vomiting and Anorexia
» Pneumonitis Major Organ Infl ammation
» Pericarditis Major Organ Infl ammation
» Hepatitis Major Organ Infl ammation
» Nephropathy Major Organ Infl ammation
» Cystitis Major Organ Infl ammation
» Risk Stratifi cation Prevention of Bacterial
» Adult Data Antimicrobial Approaches
» Pediatric Data Data regarding the utility of bacterial prophylaxis
» Risks of Prophylaxis Prevention of Bacterial
» Guidelines and Current Usage of Antibacterial Prophylaxis
» Protocols for Line Placement and Care
» Antibiotic and Ethanol Locks
» Chlorhexidine Cleansing Chlorhexidine gluconate CHG is a bactericidal
» Future Directions Prevention of Bacterial
» Risk Stratifi cation Prevention of Fungal
» Approaches to Antifungal Prophylaxis
» Guideline Recommendations for Antifungal Prophylaxis
» Limitations of Current Options for Antifungal Prophylaxis
» Risks of Prophylaxis Prevention of Fungal
» Biomarkers Prevention of Fungal
» Future Directions Prevention of Fungal
» Risk Stratifi cation Prevention of Pneumocystis
» Approaches to PCP Prophylaxis
» Summary of the Recommendations
» Future Directions Prevention of Pneumocystis
» Postexposure Chemoprophylaxis Prevention of Viral Infections
» Suppressive Therapy Prevention of Viral Infections
» Future Directions Prevention of Viral Infections
» Hand Hygiene Infection Control Practices
» Mandatory Vaccination Infection Control Practices
» Hospital Isolation Practices Infection Control Practices
» Visitor Screening Policies Infection Control Practices
» Work Restriction Infection Control Practices
» Cytomegalovirus CMV Status of Transfused Blood
» Treatment of Myelosuppression with
» Prevention of Febrile Neutropenia, Delay
» Treatment of Febrile Neutropenia
» Treatment of Myelosuppression Clinical Usage of Myeloid Growth Factors
» Comparison of Granulocyte Colony-Stimulating Factor
» Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
» Route of Administration Optimal Administration of Colony-Stimulating Factors
» Optimal Timing Optimal Administration of Colony-Stimulating Factors
» Erythropoietin Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Interleukin-11 Platelet Growth Factors
» Thrombopoietin Receptor Agonists Platelet Growth Factors
» Immune Status Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Status During Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Recovery After Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immunization Practice Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diphtheria, Tetanus, and Acellular Pertussis
» Pneumococcal Conjugate Vaccine Recommendations
» Hemophilus Infl uenzae Type b
» Inactivated Infl uenza Vaccine Although in a Cochrane review Goossen et al.
» 2009 H1N1 Pandemic Vaccine Seven studies have reported on effi cacy of the
» Live Attenuated Infl uenza Vaccine
» Meningococcal Conjugate Vaccine Recommendations
» Varicella Zoster Virus Recommendations
» Recommendations Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Treatment of Hypogammaglobulinemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vaccination of Household Contacts
» Peripherally Inserted Central Catheter
» External Tunneled Central Venous Catheter
» Implanted Port Types of Central Venous
» Catheter Insertion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Exit Site Infection Infection
» Prevention of Infection Infection
» Drug Precipitate or Lipid Residue Occlusion Thrombotic Occlusion
» Evaluation of Catheter- Related Thrombosis
» Treatment of Catheter- Related Thrombosis
» Special Considerations During Anticoagulation Therapy
» Contraindications of Anticoagulant Therapy
» Skin Antisepsis Catheter Maintenance
» Central Venous Catheter Dressings
» Hub Care Catheter Maintenance
» Central Venous Catheter Flushing and Locking
» Chlorhexidine Bathing Chlorhexidine has been shown to be effective in
» Antiseptic Needleless Connectors and Antiseptic
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