CINV
Definition
Nausea
Urge to vomit
Coupled with autonomic symptoms
sweating
paleness
tachycardia
salivation
Tachypnea
Also causes
Increased stomach tone
Increased peristalsis
Reflux
Vomiting
Strong contraction of diaphragm and chest wall
Followed by abdominal spasm and expulsion of stomach contents
Mechanism
Stimulation from the throat and pharynx
Stimulation of the chemoreceptor trigger zone
Stimulation of the cerebral cortex
See graph in lecture notes
Risk factors
Individual
Female
<60 yrs old
Exhibits high anxiety, nervousness
History of CINV in previous therapy; shows tendency to vomit due to morning sickness, motion sickness
Non- or light drinker
Drug factor
emetogenic potential
drug combination
Route of administration: oral< IV, bolus > infusion
Doses (Higher doses, higher emetogenic potential)
Dosing intensity (Dose dense therapies leave little time for patient to readjust)
Types of NV incidences
Acute NV
Occurs within minutes to hours of chemotherapy
Worst: 5-6 hours after chemo
Subsides within 24 hours
Depends on drug factors
Delayed NV
Occurs after 24 hours
Even after acute emesis has been well controlled
Last for 6-7 days
Results in loss of appetite, weight loss and distress
Associated with highly emetogenic drugs (platins, cyclophosphamide, doxorubicin)
Anticipatory NV
Associated with memory and thought
Matches previous experiences - sight, smell, sounds - of chemotherapy with emesis
Occurs 3-4 cycles into chemotherapy
Emesis begins before chemotherapy
20-65% of patients experience it; may refuse chemotherapy
Breakthrough NV
Emesis despite adequate and timely antiemetic treatment has been given
Refractory
Occurs after the first to several cycles into chemotherapy
Antiemetic therapy is no longer effective in preventing emesis
Drugs
Antihistamine
Diphenhydramine
Blocks central H1 receptor
Low emetogenic potential
Use to prevent extrapyramidal effects of metoclopramide
Phenothiazine, butyrophenone
Chlorpromazine
Binds to D, M, H1 receptors
Moderate activity against mild to moderate emesis (5-FU)
SE: hypotension, sedation, extrapyramidal effects
cannabinoids
nabilone
Only used if unresponsive to other treatment
Binds to the cerebral cortex and acts as psychoactive stimulant
Similar in efficacy to phenothiazine which increases in combination
SE: anticholinergic effects; hallucination, delusion, disorientation
corticosteroids
Unknown mechanism
Mildly effective in treating mild to moderate acute emesis and delayed emesis
Often used in combination
Benzodiazepine
Low emetogenic drug, rarely used alone
Binds to cortical receptors
Used in anticipatory NV and reduces anxiety in patietns
Sedation and hypotension
Mainstream drugs
Metoclopramide
dopamine and serotonin-3 antagonist
High doses
2-3mg/kg for 2-6 doses
30 mins prior to therapy and every 2 hours
Effective in preventing effect of highly emetogenic drugs (cisplatin)
Control of acute CINV: oral and IV have no distinction in effect
More effective when combined
SE: Extrapyramidal side effects (give diphenhydramine), dizziness, dysphoria, anxiety, depression
5HT3 antagonist (setrons)
Block 5HT3 receptors on vagal nerve and in CTZ
Highly effective against highly emetogenic drug
Corticosteroids improve effectiveness
SE: headache, dizziness, rashes, increase in liver transaminase
Superior choice for acute emesis
Aprepitant
NK1 receptor blocker
Blocks effect of substance P signalling in the brain
More effective when combined with corticosteroid and 5HT3 antagonist
Effectiveness as single agent not established
SE: dizziness, diarrhoea, mild anorexia
Consequences of CINV
Lack of nutrition
Loss of appetite, unable to eat
Decreased tolerance to chemotherapy and its side effects
Lack of effectiveness of oral chemotherapy agents
Weight loss, distress, lower compliance to therapy
Metabolic abnormalities
Hypokalemia
Metabolic alkalosis
Dehydration
Renal insufficiency secondary to chemotherapy
Memory
Anticipatory emesis
Cisplatin
81%
D1-7
D3 is peak