Classification of chemotherapy-induced nausea and vomiting


• Acute nausea and vomiting. This lasts for 12-24 hours.
• Delayed nausea and vomiting. This may occur up to 5 days after chemotherapy. It is less apparent in the case of radiotherapy.
• Anticipatory nausea and vomiting. This conditioned response results from the patient's expectation (anticipation) of nausea and vomiting.



DRUGS USED TO TREAT CHEMOTHERAPY-IINDUCED NAUSEA AND VOMITING

1- PHENOTHIAZINES
2- 5-HT3 SEROTONIN RECEPTOR BLOCKERS
3- SUBSTITUTED BENZAMIDES
4- BUTYROPHENONES
5- BENZODIAZEPINES
6- CORTICOSTEROIDS
7- CANNABINOIDS
8- SUBSTANCE P/NEUROKININ-1 RECEPTOR BLOCKE



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1- PHENOTHIAZINES
A- Prochlorperazine (Compazine)
B- Thiethylperazine (Torecan)
Mechanism of action: they act by blocking dopamine receptors, they are effective against low or moderately emetogenic chemotherapeutic agents
Side effects: hypotension, restlessness, extrapyramidal symptoms, sedation.



2- 5-HT3 SEROTONIN RECEPTOR BLOCKERS
A- Dolasetron (Anzemet)
B- Granisetron (Kytril)
C- Ondansetron (Zofran)
D- palonosetron (Aloxi)
Long duration of action, effective against all grades of emetogenic therapy
Used with caution in hepatic insufficiency (metabolite in liver)
Side effects: headache, dolasetron can cause ECG changes (as prolongation of QT intervals).



3- SUBSTITUTED BENZAMIDES
A- Metoclopramide (Reglan, Clopra, Octamide)
In highly doses, it is effective against the highly emetogenic cisplatin
Side effects: antidopaminergic as sedation, diarrhea. Extrapyramidal symptoms.



4- BUTYROPHENONES
A- Domperidone (Motilium)
B- droperidol (Inapsine)
C- haloperidol (Haloperidol)
Mechanism of action: block dopamine receptors. Moderately antiemetic.
Droperidol used for sedation in endoscopy & surgery.



5- BENZODIAZEPINES
A- Alprazolam (Xanax)
B- lorazepam (Ativan)
Low antiemetic potency. Antianxiety drugs.



6- CORTICOSTEROIDS
A- Dexamethasone (Decadron)
B- Methylprednisolone (Solu-Medrol)
Mechanism of action: not known but may be it block the prostaglandins, effective against mildly to moderately emetogenic chemotherapy (used in combination)
Side effects: insomnia, hyperglycemia in DM patients.



7- CANNABINOIDS
A- Dronabinol (Marinol)
B- nabilone
Marijuana derivatives, effective against moderately emetogenic chemotherapy
Side effects: dysphoria, hallucination, sedation, vertigo, and disorientation.



8- SUBSTANCE P/NEUROKININ-1 RECEPTOR BLOCKER
A- Aprepitant (Emend)
Mechanism of action: it blocks neurokinin receptors. Administred with dexamethasone and palonosetron
Its metabolism by CYP3A4
Side effects: constipation, fatigue.

Combination
• Corticosteroids (as dexamethasone) increase antiemetic effect when given with (high dose metoclopramide, 5-HT3 antagonist, phenothiazine, butyrophenone, a cannabinoid, or a benzodiazepine)
• Antihistamine (as diphenhyramide) given with high dose metoclopramide to reduce extrapyramidal symptoms.
• Cannabinoid with prochlorperazine to reduce dysphoria.




Summary
• Nausea and vomiting is a major problem in cancer therapy that can lead to some patients refusing further, potentially curative treatment
• There are three types of emesis resulting from chemotherapy and radiotherapy; acute, delayed and anticipatory. Each has a different aetiology, and should be treated differently.
• 5-HT3 receptor antagonists are the most effective treatment for acute emesis resulting from cancer chemotherapy.
• A wider range of agents, including anti-histamines and dopamine antagonists is effective against nausea and vomiting resulting from radiotherapy.
• 5-HT3 receptor antagonists are less effective against delayed emesis resulting from treatment with agents such as cisplatin.
• The best treatment of anticipatory emesis is effective control

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