“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.