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5-HT Receptor Antagonists
The discovery of the
role of 5-HT3 receptors in the emetic response
to cytotoxic drugs eventually led to the introduction of the highly
specific 5-HT3 receptor antagonists (Miner
et al., 1986), which are increasingly used for the treatment
of chemotherapy-induced emesis (Roscoe
et al., 2000). Introduction of new antiemetics has generally
been paralleled by the availability of more highly emetogenic
chemotherapeutic agents and combination regimens requiring even
stronger antiemetics for symptom control. Not surprisingly, the
advent of the 5-HT3 receptor antagonist
antiemetics (see Table below) was hailed with enthusiasm by patients
and medical practitioners alike (Ettinger
et al., 1998).
| 5-HT3
Receptor Antagonist Antiemetics
|
|---|
| Generic
name
| Brand
name
| Year
introduced
|
|---|
| ondansetron
| Zofran® | 1991 |
| granisetron
| Kytril® | 1994 |
| tropisetron
| Navoban® | Not
licensed in the United States |
| dolasetron
mesylate | Anzemet® | 1997 |
|
palonosetron
hydrochloride
| Aloxi | 2003 |
|
The 5-HT3
receptor antagonists have been shown to be clinically more effective
in controlling emesis, particularly that which is caused by regimens
containing high-dose cisplatin, than previously available agents
(de
Mulder et al., 1990; Marty et al.,
1990).
Disappointingly however,
these drugs do not appear to be more effective than previous antiemetics
in reducing nausea, as indicated in the data presented in Table
3 (Morrow
et al., 1998). In addition, the 5-HT3
antiemetics may become less effective over repeated chemotherapy
administrations (du Bois et al., 1991;
du Bois, 1998), and they remain expensive.
The most common adverse effects of 5-HT3
receptor antagonists are headache and diarrhea or constipation,
which develop in up to 8% to 20% of patients. These symptoms are
generally mild and usually do not lead to patients' refusal to
continue on the medication (Stewart
et al., 1995; Navari
et al., 1994).
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