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Oncology I-II

Oncology Side Effects & Chemotherapy-Induced Nausea and Vomiting

TermDefinition
What is the proposed MOA Of chemotherapy induced nausea and vomiting? - chemotherapeutic agent target highly dividing cells - GI track is highly dividing norma cells - destruction of the inner lining/epithelium cells --> side effects
what are some factors that increases the risk of chemotherapy induced nausea and vomiting? - female - <50 - dehydration - h/o of motion sickness - h/o of N/V
what are some of the recommendations to manage chemotherapy induced nausea and vomiting? 1- give anti emetic drug 30 min prior to chemo cycle 2- give home med to manage breakthrough nausea and vomiting
what are the four types of nausea/vomiting induced chemotherapy? 1- acute ( within 24hr post chemo) 2- delayed ( 1-7 days post chemo) 3- anticipatory ( prior to chemo) 4- breakthrough ( regardless of anti emetic tx)
Which major neurotransmitters are responsible for the following? 1- acute N/V 2- delayed N/V 1- acute: serotonin 5-TH3 2- delayed: substance-P ( neurokinin-1)
which class of drugs is preferred to treat acute, delayed, breakthrough, and anticipatory N/V? 1- Acute: 5-TH-3 blocker 2- Delayed: 5-TH-3 blocker + substance-P blocker ( NK-1) + steroid 3- anticipatory: benzodiazepines 4- breakthrough: - 5-HT-3 RAs - dopamine receptor blocker - cannabinoids
What is the drug of choice of 5-TH3 blocker to treat delayed N/V? - the only FDA approved is palonosetron ( alone)
What are the three main classification of emetic risk potential groups? 1- high emetic group ( >90% risk) 2- moderate emetic group ( 30-90%) 3- low emetic group ( <30-10%) 4- minimal risk group ( < 10%)
Which drugs are highly emetogenic chemotherapeutic agents? C2DEF 1- Cisplatin 2- doxorubicin/ epirubicin 3- ifosfamide/ cyclophosphamide
which drugs are Minimal rISK ( <10) emetogenic chemotherapeutic agents? - monoclonal Ab - TKIs
what is the goal of therapy for CINV? - prevent N/V - schedule drugs prior to chemo and after chemo - FYI: N/V for high emetogenic drug: risk for 3 days post chemo FYI: N/V for moderate emetogemic drug : risk for 2 days post chemo
What is the difference in therapy between emetogenic agents? - high emetogenic drugs: 3 drugs( can add one more if needed) - moderate emetogenic drugs: 2-3 drugs ( can add one more if needed ) - low emetogenic drugs: 1 drugs
What are some example of 5-HT-3 blocker? - ondansetron - granisetron - dolasetron - palonosetron ( only FDA approved for moderate risk )
What are some example of NK-1R blocker? - aprepotant PO - Fosaprepitant IV - Rolaapitant
What is the approved steroid medication to prevent CINV? - dexamethasone
What are some other drugs that can be added to CINV regimen? - olanzapine - lorazepam
what is an example of a combination drug approved to prevent CINV? - Akynzeo - consist of : 1- netupitant 2- palonosetron
What antiemetic regimen is appropriate for a patient receiving cisplatin chemo-based therapy? ** first cisplatin is high emetogenic risk chemo - at least 3 drugs: 1- 5HT-3 blocker + NK-blocker + steroid 2- Akynzeo + steroid 3- Steroid + olanzapine + palonosetron
KEY point in antiemetic regimen in patient receiving high emetogenic chemo? - steroid + 5-HT-3 blocker + other drug ( olnazapine, NK-1A) - steroid + combo drug - May add lorazepam - May use 4 drugs regimen ( steroid + 5-HT-3+ NK-1A+ olanzapine)
What antiemetic regimen is appropriate for patient receiving cytarabine 1gram ? - moderate emetogenic drug - 2-3 drugs maybe used - same regimen as high emetogenic - steroid+ 5-HT-3+NK-1 - Steroid + 5-HT-3 only - Steroid + 5-HT-3 + olanzapine - steroid + combo
what antiemetic regimen is appropriate for patient receiving Paclitaxel? - low risk - one drug is enough - steroid - 5-HT3 - dopamine receptor blocker: 1- prochlorperazine 2- metoclopramide
Which drug may used in patient experiencing anticipatory CINV? - lorazepam ** benzodiazepines is indicated in anticipatory CINV
What is breakthrough N/V? - N/V despite receiving antiemetic drug regimen
what are some drugs that can be used to in patient experiencing breakthrough N/V? - 5-HT-3 RAs - dopamine receptor blocker - cannabinoids
what are some of the common side effect of 5-HT-3 blocker? - migraine like headache - constipation
what are some example of dopamine receptor blocker? ( azine) - prochlorperazine - promethazine - metoclopramide
what are the common side effect of dopamine receptor blocker? - sedation - extrapyramidal symptoms ( EPS) such as acute dystonic rxn in younger pt
What is the recommended treatment for acute dystonic reactions? ( reversible EPS)? - anticholinergic 1- benztropine 2- diphenhydramine
what are some other class of medication can be used as 2nd line ( they may/may not be legally approved in some states CI )? - The cannabinoids 1- dronabinol (marinol, syndros) 2- nabilone ( cesamet)
What is the MOA of cannabinoids ( dronabinol and nabinol) in CINV? - delta-9-tetrahydrocannabinol - naturally occurring compound - cannabis sative ( marijuana)
what are some of dronabinol or nabinol side effect? cannabinoids drugs 1- sedation 2- dysphoria 3- euphoria
What is the MOA of substance P/Neurokinin-1 receptor blocker? - Augmenting the antiemetic activity of 5-HT3 blocker and steroid - blocking substance P/neurokinin-1 receptor
what is substance P/Neurokinin-1 receptor blocker suffix? epitant
Which antipsychotic drug the use of aprepitant and fosaprepitant is C/I? - pimozide - cyp 3A4 substrate
Which gastroprokinetic drug the use of aprepitant and fosaprepitant is C/I? cisapride cype 3A4 substrate and 5-HT4 agonist
which anti schizophrenic drug the use of rolapitant is C/I? thioridazine cyp 2D6 substrate
What are some common side effect of substance P/ neurokinin1 receptor blocker? - dizziness - weak/fatigue - constipation - hiccups ( involuntary diaphragm movements)
Which of the substance P/Neurokinin-1 receptor blocker are CYP 3A4 substrates? - aprepitant - fosaprepitant - netupitant
which of the substance P/Neurokinin 1 receptor blocker are CYP 2D6 substrates? rolapitant
The use of Substance P/Neurokinin-1 blocker concurrently with dexamethasone requires a reduction of dexamethasone except ? except in rolapitant as it's CYP 2D6 substrate
Which drugs of substance P/neurokinin1 blocker require dexamethasone dose adjustment ( reduction) when used concurrently? - aprepitant - netupitant
Which substance P/neurokinin 1 blocker requires dosing before ( day 1) and after chemotherapy for two days ( day II & III)? aprepitant ( 3 DAYS DOSING) Day 1: 125 mg 1 h/r prior to chemo Day II, III: 80 mg
Which substance P/ Neurokinin 1 blocker drugs require one day dosing prior to chemotherapy ( DAY 1) ? - fosaprepitant: 150 mg IV 30 min prior to chemo - Akynzeo: 300/0.5 mg orally 1 hr prior to chemo - rolapitant: 180 mg 1-2 hrs prior to chemo
What is the MOA of 5-HT3 receptor blocker? - blocks serotonin receptor centrally ( chemoreceptor trigger zone) and peripherally ( vagal nerve terminals)
What is the recommended dosing of 5-TH-3 receptor blocker? - ONCE on DAY 1 prior to chemo - patch is the only exception, start before DAY 1
What are some examples of 5-TH-3 receptor blocker durgs? - ondansetron - Granisetron - dolasetron - palonosetron
Which dopamine promoter is considered C/I in patient taking ondansetron? - apomorphine ** the use of apomorphine with ondansetron increases the hypotensive effect of apomorphine
Which 5-HT-3 receptor blocker has CV effect in particular increases in QT interval ( torsade de pointes) ? - dose dependent - IV 1- IV ondansetron ( zofran) 2- IV granisetron (kytril) 3- IV dolasetron ( anzemet) 4- IV palonosetron ( aloxi)
Which 5-HT-3 receptor blocker has the highest risk of inducing QT prolongation ( torsade de pointes)? - IV dolasetron ( aznemet) highest risk of QT prolongation - NOT indicated for CINV tx
Which 5-HT3 blocker induces constipation, progressive ileum and gastric distension? - granisetron SC injection ( sustol)
Which 5-HT3 drug is available only as IV? palonosetron Aloxi
which 5-HT3 drug is available as oral combination with NK-1 blocker? palonosetron+ netupitant = akynzeo
what are some of the common side effects of 5-HT3 blocker? - headache - fatigue - dizziness - constipation - injection rxn ( sustol SC injection)
what are some considerations in using Sancuso ( granisetron patch)? - prior to day 1 chemo - duration for 24 hr - apply Q 1-2 days prior to chemo - may leave it for a week
When is the use of dexamethasone in CINV is C/I ? - systemic fungal infection - cerebral malaria
what are some of dexamethasone side effect ? - short term use: 1- increases wt 2- fluid retention*** 3- insomnia 4- GI upset 4- emotional instability
What are the side effect of high dose dexamethasone? - high blood pressure - increases blood glucose
what is the recommended dosing of dexamethasone in CINV on DAY 1 prior to chemo ? - for high, moderate, low risk the first dose is fixed : 12 mg PO/IV on day 1 of chemo - FOR DAY 1 regardless of emetognicity, 12 mg PO/IV on day 1 except in high regimen, may start @ either 12 mg or 20 mg
What is the recommended dosing of dexamethasone with aprepitant or netupitant in high emetogenic chemo therapy? 4 days dosing - Day 1: 12 mg PO/IV - Day 2, 3,4 : 8 mg PO
What is the recommended dosing of dexamethasone with fosaprepitant in high emetogeic chemo therapy? 4 days dosing - Day1: 12 mg PO/IV - Day2: 8 mg/ day - Day 3and4: 8 mg BID
what is the recommended dosing of dexamethasone with rolapitant in high emetogenic chemo therapy? 4 days dosing - Day 1: 12 mg PO/IV - Day 2-4: 8 mg BID
what is the recommended dosing of dexamethasone in moderate emetogenic chemo therapy? 3 days dosing - Day1: 12 mg PO/IV - Day 2-3: 8 mg /day
what is the recommended dosing of dexamethasone in low risk emetogenic chemo therapy? - ONLY at the day of chemo - 12 mg PO/IV
what is the MOA of dopamine receptor blocker? blocks dopamine receptor and chemoreceptor trigger zone
What are the most common dopamine receptor blocker drugs are used in CINV? 1- prochlorperazine 2- promethazine 3- metolopramide 4- droperidol
Which dopamine receptor blocker increases the risk of mortality in elderly patient with dementia related psychosis ( BBW)? - prochlorperazine ( mortality)
Which dopamine receptor blocker is not indicated in patient less than 2 years due to the risk of respiratory depression ( BBW)? - promethazine ( respiratory depression)
Which dopamine receptor blocker should not be given as SC or intra arterial? - promethazine
What is the preferred route of administration of promethazine? - DEEP IM injection - NEVER GIVE SC - IV can cause tissue injury if extravasation occurs
What is a complication of administering promethazine as IV? - serious tissue injury if extravasation occurs
Which dopamine receptor blocker can cause tardive dyskinesia ( TD) which might be irreversible ( BBW) ? Metoclopramide
What are some risk factors that increases the risk of developing tardive dyskinesia in patient receiving Metocopramide? - increases duration - increases total cumulative dose ( avoid > 12 weeks use)
Which dopamine receptor blocker can cause QT prolongation and serious arrhythmias? droperidol IV injection
What should be done prior to using droperidol IV ( dopamine receptor blocker)? - Since the droperidol IV can induce QT prolongation + arrhythmias 1- 12 lead ECG prior to droperidol IV 2- 12 lead ECG 2-3 hours after droperidol IV
when is the use of droperidol IV C/I? - if pt has a prolonged QT baseline
which patient population the use of dopamine receptor blocker should be avoided? - pt with Parkinson ds as it exacerbate its sxs
which dopamine receptor blocker needs dose adjustment in patient with renal impairment eGFR < 40ml/min metoclopramide - give 1/2 the dose
which dopamine receptor blocker is indicated only post operative n/v as it increases the risk of QT prolongation/ arrhythmias ? droperidol IV
Which dopamine receptor blocker is available as suppository PR route of administration? - prochlorperazine - promethazine
which dopamine receptor blocker is available as IM injection and considered the best ROD? - promethazine
What is the difference in dosing metoclopramide in high emetic chemo regimen? - usually dosed 10-40 mg every 6 hrs PRN- fixed - in high emetic : 0.5-2 mg/kg every 6 hrs prn -- PER Kg of the patient
What are the common side effect of dopamine receptor blockers? - sedation - lethargy - QT prolongation - hypotension - constipation except methoclopramide and droperidol
What are some serious side effects of dopamine receptor blockers? - neuroleptic malignant syndrome -acute EPS ( in children) - reduce the seizure threshold
which class of drug is used to treat dopamine receptor blockers induced acute EPS? - anticholinergic 1- benztropine 2- diphenhydramine
What is the MOA of Cannabinoids in CINV? - activating the cannabinoids receptor in CNS - inhibiting the vomiting center at medulla oblongata
What are the most common cannabinoid drugs used in CINV? 1- dronabinol CIII 2- nabilone CII
what is the difference in class between DronaBINOL and DroPERIDOL? cannabinoids vs dopamine receptor blocker
What are the dosage forms of dronabinol? - capsule - solution ( 50% alcohol)
what are some side effects of cannabinoids? 1- somnolence 2- euphoria/ dysphoria 3- increase appetite 4- hypotension 5- lowers seizure threshold
what are some common factors to consider prior to starting patients on cannabinoids? - psychiatric disorders - substance abuse
what is the recommended dronabinol dosing in CINV? - 5mg/m2 prior to chemo - Q2-4 hr PRN - max of 6 does/day
what is the recommended nabilone dosing in CINV? - 1-2 mg BID/day - up to 48hrs
Created by: Smoham38