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Anti-emetics in chemotherapy

Highest therapeutic index medication

5-HT3 serotonin receptor antagonists

Corticosteroids

NK1 receptor antagonists

Lower therapeutic index medication

Metoclopramide, Butyrophenones,

Phenothiazines, Cannabinoids.Adjunctive drugs

Benzodiazepines

antihistamines

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(5HT3 inhibitor)

/

ondansetron 8~32mggranisetron 1~3mgtropisetron 5mg

ondansetron 8~32mggranisetron 1~3mgtropisetron 5mgdexamethasone metoclopramidedexamethasone metoclopramide

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cisplatin(>50mg/m2/day)carmustine(250mg /m2 /day),cyclophosphamide(>1500mg/m2/day)methotrexate (1.2gm/m2 /day)

cisplatin(30mg/m2/day

50mg/m2/day)carmustine(

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(NK-1 inhibitor)

dexamethasone5-HT3

5-HT3

carmustine(250mg/m2 /day),cyclophosphamide

(>1500mg/m2/day), methotrexate1.2gm/m2 /daycisplatin>50mg/m2

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Pathophysiology of Nause and Vomiting

The emetic center receives input from:

Chemotehrapy trigger zone(CTZ)

Mediated by dopamine, serotonin, substance-PVagal afferent center

Mediated by serotonin

Cerebral cortex May be involved with anticipator N/V

Mediated by dopamine and serotonin

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Chemotherapy induced Emesis

Acute emesis()

Delayed emesis()

Anticipatory emesis()

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Acute Delayed Anticipatory

The intensity

peaks after 2-6hrs, occurs more

often and tend to

be more severe

than delayedemetic episodes

Peak incidence

occurring at 48-72h. Commonly

found with

cisplatin,

carboplatin,cyclophosphamid

e,doxorubicin

10-60% incidence

rate

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Other causes of emesis

Partial or complete bowel obstruction

Vestibular dysfunction

Brain metastases

Electrolyte imbalance

Uremia

Concomitant drug treatments opiates

Gastroparesis

Psychophysiologic

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Principles of emesis control

Prevention of nausea/vomiting is the goal

Emesis risk last for at least 4 days

Use the lowest tested fully effective dose

Intravenous and oral formulations areequally effective and safe

Consider toxicity of specific antiemetic

Choice of antiemetic based on emetic riskof the chemotherapy as well as patientfactors

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Factors increase susceptibility to CINV

Hx of motion sicknessHx of moderate/severe sickness duringpregnancy

Recent exposure to anesthetics

Recent abdominal, ophthalmic, or cranialsurgery

Concomitant use of nauseogenic drugs

Raised BUNAnxiety

Female gender

Asian ethnicity

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Factors decrease susceptibility to CINV

Alcohol consumption

Smoking

Old ageCannabinoid use

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Acute Emesis

Vomiting occurring 0-24 hrs after therapy

Emetic risk categories

High

Moderate

Low

Minimal

Classification based on experience rather

than on specific data

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Anti-emetic agent

Chemical class Drugs Action sites

5HT3 antagonist Ondansetron,

Granisetron,

Tropisetron

CTZ & peripheral

5HT3

NK-1 antagonist Aprepitant CTZ substance-P

Corticosteroid Dexamethasone Prostaglandin

BZE Lorazepam,

Diazepam

Sedative &

anxiolytic

Antihistamines Diphehydramine Vestibular nucleus

Dopamine & 5HT3

receptor

Metoclopramide Dopamine

antagonist

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Emetic potential Acute emesis Delayed emesis

High5HT3 + Dex +

NK1Dex + NK1

Moderate 5HT3 + Dex Dex

Low Dex + MCP Nil

Minimal Nil Nil

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Antiemetics for radiation