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27 Cards in this Set
- Front
- Back
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Mechanisms for chemo induced nausea and vomitting (CINV)
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Stimulation of chemorecepetor trigger zone (CTZ)
-in area postrema of brain -invokes release of neurotransmitters which activate brainstem vomiting center Peripheral mechanism -damage of GI mucosa resulting in release of neurotransmitters (serotonin) -stimulation of GI neurotransmitter receptors by vagal afferents send signals to brainstem vomiting center Cortical mechanisms -direct cerebral activation (serotonin) -indirect (psychogenic mechanisms) Vestibular mechanisms Alterations of taste and smell |
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Neurotransmitters in CINV pathway
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Serotonin and Substance P
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Acute phase of CINV
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Most common
Begins 1 to 2 hours, peaks 4 to 10 hours, resolves within 12 to 24 hours Usually associated with high frequency and severity Serotonin antagonists are most effective Neurokinin antagonists are also effective -locks up substance P FYI worst emetic is cisplatin |
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Delayed phase of CINV
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Begins 1 to 5 days after chemo, peaks 48 to 72 hours
Less severe than acute N/V, longer duration Associated with high-dose cyclophosphamide, mitomycin-C, cisplatin, doxorubicin, and ifosfamide Neurokinin-1 antagonists are most effective |
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Anticipatory phase of CINV
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Not associated with a time frame
Conditioned response Usually prior history of severe N/V Stimulated from environment Occurs in up to 25% of patients Often refractory to therapy Treat with anti-anxiety drugs |
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Serotonin (5HT3) Receptor antagonists: overview, efficacy, adverse effects
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Blocks serotonin both centrally and peripherally
Effective for acute N/V but not any more effective for delayed N/V than other therapies Most effective when given 30 minutes prior to chemo Increase efficacy when given with corticosteroids (60% vs 90%) Adverse effects: headache, constipation, diarrhea, EKG changes (concern only with underlying arrhythmias) |
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5HT3 receptor antagonists
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Ondansetron (Zofran)
Granisetron (Kytril) Dolasetron (Anzemet) Palonosetron (Aloxi) |
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Neurokinin-1 (NK-1) receptor antagonists: overview, indications
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Aprepitant (Emend)
Inhibits Substance P Indicated for prevention of acute and delayed CINV in combination with serotonin antagonists and corticosteroids Part of combination regimen with a 5HT3 receptor antagonist plus dexamethasone |
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NK-1 receptor antagonist adverse effects
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Asthenia/fatigue (18%)
Nausea Hiccups Diarrhea Somnolence |
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Aprepitant (Emend): Drug interactions
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Steroids should be decreased by 50% when given IV or 25% when given PO
Should be used in caution when admistering agents that are metabolized by CYP3A4 Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of drugs also metabolized by CYP3A4 |
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Dopamine receptor antagonists
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Phenothiazines
Butyrophenones Substituted benzamide |
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Phenothiazines
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Effective for delayed N/V
Adverse effects -akathisia - lorazepam can help -dystonia - diphenhydramine or benztropine can help -sedation - more common with promethazine Prochlorperazine is a more potent antiemetic in cancer patients but has a higher incidence of akathisia and dystonia |
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Substituted benzamide
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Block dopamine in CTZ and peripherally
-increase esophageal sphincter tone -improve gastric emptying -increase transit through small bowel Adverse effect -extrapyramidal, restlessness, sedation, fatigue, nausea, and diarrhea (dexamethasone may decrease diarrhea) |
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Miscellaneous anti-emetics
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Benzodiazepines (anti-anxiety)
-lorazepam, diazepam Corticosteroids -dexamethasone Cannabinoids -dronabinol Anticholinergics -scopolamine |
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Benzodiazepines
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Possess amnesic, anxiolytic, and sedative properties
Used for anticipatory nausea Not effective for preventing emesis and is usually given with other antiemetics |
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Corticosteroids
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Increase appetite, improve mood and sense of well being
Immunosuppressive properties May increase differentiation of WBC and therefore is not given in AML Adverse effects: mood changes, anxiety, euphoria, headache, metallic taste, abdominal discomfort Dexamethasone is most effective |
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Cannabinoids: Dronabinol (Marinol)
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Less effective than metoclopramide but more effective than phenothiazines
Not effective with highly emetogenicity Adverse events: mood changes, dysphoria, memory loss, hallucinations, blurred vision, hypotension, tachycardia Beneficial with younger patients |
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Anticholinergics
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Beneficial for nausea associated with movement
Scopolamine Dry them out (anticholinergic) |
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What to use? Acute, delayed, and rescue
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Acute:
5HT3 + dexamethasone + aprepitant - Day 1 Aprepitant + dexamethasone - Day 2 and 3 Delayed and rescue: -Metoclopramide -Dronabinol -Phenothiazines |
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G-CSF (Filgrastim)
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Supports proliferation of neutrophils
Stimulates neutrophil function No effect on mature eosinophils and macrophages Adverse effects: -Bone pain --lumbar, sternal, and pelvic areas --common during initiation of therapy and times of rapid growth --may reflect increased bone marrow activity --pain responsive to acetaminophen or NSAIDS |
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Pegylated filgrastim (Neulasta)
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This larger chemical structure makes clearance slower and therefore allows administration once afther chemo
Cleared by neutrophils so as the white blood cells recover then they are able to clear the drug (patient dependent) |
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GM-CSF, Sargramostim (Leukine)
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Stimulates CFU-GM and CFU-GEMM to increase neutrophils, macrophages, monocytes, eosinophils
Adverse effects: -Constitutional symptoms --fever (responds well to antipyretics, may have less with SQ administration) --myalgias --arthralgias -bone pain -skin reactions -pleural and pericardial effusions -first-dose effect |
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Erythropoieten stimulating agents (ESA)
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Enhance RBC production
Decreases need for RBC transfusions Patients should have Hgb <10 or HCT < 30% Monitor iron stores Requires 2-6 weeks to see response Adverse effects: HTN HA Increased clotting Iron deficiency anemia Seizures Achiness and cold sensation in long bones Pyrexia Increased risk of death for patients not receiving concurrent chemo -reason for REMS program (renal) |
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Darbopoietin (AraNesp)
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ESA
Larger molecule with more carbohydrate groups to allow for slower elimination |
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IL-11: Oprelvekin (Neumega)
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Never use because 60-70% of time you get atrial arrhythmias
Activity -promotes megakaryocyte production -prevents sever thrombocytopenia Continue until plt >50,000 Clinical use has not been shown to prevent transfusions of platelets because transfusion of platelets does not occur until count <10,000 |
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Romiplastim (Nplate)
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Thrombopoiesis stimulating protein
Increases platelets in patients with chronic ITP |
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Eltrombopag (Promacta)
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Thrombopoiesis stimulating protein
Increases platelets in patients with chronic ITP Orally only Must avoid antacids |
