“TREATMENT OF NAUSEA AND VOMITING”

James Hallenbeck, MD

What’s the difference between Compazine (prochlorperazine) and Phenergan (promethazine)? By understanding the pathophysiology of nausea and targeting antiemetics to specific receptors, therapy can be optimized and side-effects minimized. An easy way to remember the causes of vomiting is to use the VOMIT acronym. In the table below receptors involved in different types of nausea are highlighted using this acronym. Blockade of these receptors allows rational, focused therapy.

Type of nausea	Receptors causing nausea	Drug class useful	Examples of DOC
Vestibular	Cholinergic, Histaminic	Anticholinergic, Antihistaminic	Scopolamine patch Promethazine
Obstruction of Bowel caused by constipation *	Cholinergic, Histaminic, ? 5HT3	Stimulate myenteric plexus	Senna products
DysMotility of upper gut **	Cholinergic, Histaminic, ? 5HT3	Prokinetics stimulate 5HT4 receptors	Metoclopramide Cisapride
Infection, Inflammation	Cholinergic, Histaminic, ? 5HT3	Anticholinergic, Antihistaminic	Promethazine
Toxins stimulating the CTZ in the brain such as Opioids***	Dopamine 2, 5HT3	Antidopaminergic, 5HT3 Antagonist	Prochlorperazine, Haloperidol, Ondansetron

* The most common cause of bowel obstruction is constipation. This is especially problematic in patients on opioids. Treatment of nausea related to mechanical bowel obstruction is controversial and stimulants, such as senna may be inappropriate, especially if cramping is present.

** Dysmotility of the upper gut is a common, under-appreciated cause of nausea, especially in patients on opioids or anticholinergic drugs, both of which slow gut motility. Patients typically complain of early satiety in contrast to other patients, who have fasting nausea. Metoclopramide is contraindicated in Parkinson’s Disease and renal failure. Cisapride has numerous drug-drug interactions, so beware! Both prokinetic work poorly if anticholinergic drugs are co-administered. So don’t give promethazine for this form of nausea!

*** Rising serum levels of opioids stimulate the chemotactic trigger zone (CTZ), causing nausea. Minimizing fluctuating opioid levels, by using long-acting agents where possible, can limit this form of nausea. Prochlorperazine is the first-line suppository, haloperidol may be used orally or parenterally. Ondansetron, a 5HT3 antagonist is a second-line agent that can be used where antidopaminergic drugs are contraindicated, such as in Parkinson’s Disease.

Additional pearl: There is no good evidence supporting the use of lorazepam as a sole agent for nausea. Sedated patients may be more prone to aspiration. Listed below is a comparison of some commonly used antiemetics:

Scopolamine: a very potent, pure anticholinergic agent.

Promethazine (Phenergan): antihistamine with potent anticholinergic properties, very weak antidopaminergic agent. (So bad for opioid related nausea.)

Prochlorperazine (Compazine): Potent antidopaminergic, weak antihistamine, anticholinergic agent.

Haloperidol: Very potent anti-dopaminergic agent.

As you can see, Phenergan and Compazine are very different drugs. Phenergan is useful for vertigo and gastroenteritis due to infections and inflammation. Compazine is preferred for opioid related nausea.

References:

· Mannix KA. Palliation of nausea and vomiting. Oxford Text Palliative Med. Second ed. 1998. Oxford. U. Press, NY.489-499.

· Storey P, Knight CF. UNIPAC Four: Management of Selected Nonpain Symptoms in the Terminally Ill. 1996. American Academy of Hospice and Palliative Medicine. Can order via www.aahpm.org.

Edward E. Rylander, M.D.

Diplomat American Board of Family Practice.

Diplomat American Board of Palliative Medicine.