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27 Cards in this Set

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Mechanisms for chemo induced nausea and vomitting (CINV)
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
Neurotransmitters in CINV pathway
Serotonin and Substance P
Acute phase of CINV
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
Delayed phase of CINV
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
Anticipatory phase of CINV
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
Serotonin (5HT3) Receptor antagonists: overview, efficacy, adverse effects
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)
5HT3 receptor antagonists
Ondansetron (Zofran)
Granisetron (Kytril)
Dolasetron (Anzemet)
Palonosetron (Aloxi)
Neurokinin-1 (NK-1) receptor antagonists: overview, indications
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
NK-1 receptor antagonist adverse effects
Asthenia/fatigue (18%)
Nausea
Hiccups
Diarrhea
Somnolence
Aprepitant (Emend): Drug interactions
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
Dopamine receptor antagonists
Phenothiazines
Butyrophenones
Substituted benzamide
Phenothiazines
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
Substituted benzamide
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)
Miscellaneous anti-emetics
Benzodiazepines (anti-anxiety)
-lorazepam, diazepam
Corticosteroids
-dexamethasone
Cannabinoids
-dronabinol
Anticholinergics
-scopolamine
Benzodiazepines
Possess amnesic, anxiolytic, and sedative properties
Used for anticipatory nausea
Not effective for preventing emesis and is usually given with other antiemetics
Corticosteroids
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
Cannabinoids: Dronabinol (Marinol)
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
Anticholinergics
Beneficial for nausea associated with movement
Scopolamine
Dry them out (anticholinergic)
What to use? Acute, delayed, and rescue
Acute:
5HT3 + dexamethasone + aprepitant - Day 1
Aprepitant + dexamethasone - Day 2 and 3

Delayed and rescue:
-Metoclopramide
-Dronabinol
-Phenothiazines
G-CSF (Filgrastim)
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
Pegylated filgrastim (Neulasta)
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)
GM-CSF, Sargramostim (Leukine)
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
Erythropoieten stimulating agents (ESA)
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)
Darbopoietin (AraNesp)
ESA
Larger molecule with more carbohydrate groups to allow for slower elimination
IL-11: Oprelvekin (Neumega)
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
Romiplastim (Nplate)
Thrombopoiesis stimulating protein
Increases platelets in patients with chronic ITP
Eltrombopag (Promacta)
Thrombopoiesis stimulating protein
Increases platelets in patients with chronic ITP
Orally only
Must avoid antacids