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



:::::::::::::::::::::::::::::::::::::::::::::::::: :::::::::::::::::::::::::::::::::::::::::::::::::: :::::::::::::::::::::::::::::::::::::::

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