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Chapter 91 Pain Management and Antiemetic Therapy in Hematologic Disorders 1485

The side effects, which may be caused by the interaction of cannabinoids are mostly reserved for patients with difficult-to-treat,
metoclopramide with dopamine receptors, can be quite trouble- refractory nausea and vomiting or as a rescue agent. Younger patients
some. They include akathisia, dystonic reactions (age related), find cannabinoids more effective than do older patients, likely due
sedation, and diarrhea. Benzodiazepines such as lorazepam and to better tolerated side effects associated with the therapeutic doses
β-blockers such as propranolol can prevent or reverse the akathisia, of these agents. The cannabinoids cause ataxia, dry mouth, orthostatic
and diphenhydramine or benztropine can prevent or reverse the hypotension and dizziness, euphoria (or dysphoria), and a feeling of
dystonias. However, these agents induce additional side effects, being “high.” 75
including dry mouth and sedation. Short-term, high-dose meto-
clopramide or long-term use at usual doses has been associated Other Drugs
with persistent and disabling movement disorders, especially tardive Other agents that are more active than placebo include the butyro-
dyskinesias. phenones haloperidol and droperidol, and the phenothiazine pro-
chlorperazine. These agents are less effective drugs than the agents
Neurokinin-1 Inhibitors previously mentioned, and all cause sedation. The butyrophenones
Substance P can cause emesis, and it appears to play a role in produce dystonic reactions, akathisia, and occasionally hypotension.
chemotherapy-related nausea and vomiting. Its effects are mediated Scopolamine, a centrally acting anticholinergic, can be effective for
9
through NK-1 receptors. Agents that cross the blood–brain barrier patients with a vertiginous component to their nausea.
and inhibit NK-1 activity (e.g., aprepitant, netupitant) are more
effective than a 5-HT3 RA and dexamethasone alone in moderating
acute chemotherapy-related nausea and vomiting, and they are par- CONCLUSION
ticularly effective in decreasing delayed nausea and vomiting occur-
ring after highly and moderately emetogenic chemotherapy (HEC Pain remains one of the most distressing and debilitating symptoms
and MEC). 9,71 Aprepitant is an inhibitor of CYP3A4 and therefore in patients with hematological disorders. Whether secondary to the
may cause elevation of chemotherapy agents primarily metabolized disease process, iatrogenic, diagnostic, or therapeutic interventions,
by this route; however, these elevations are not considered clinically or related complications, pain is frequently underappreciated and
significant, and there are no recommend dose adjustments. Aprepi- undertreated. A methodological approach to evaluate and manage
tant can cause significant decreases in the prolongation of the inter- pain is recommended. Knowledge of the wide range of pharmacologic
national normalized ratio induced by warfarin and increases the area and nonpharmacological interventions is essential for the clinician
under the curve of dexamethasone. The maximum dose of dexa- managing pain. Pain refractory to standard approaches should be
methasone in combination with aprepitant is 12 mg. Fosaprepitant, referred to pain or palliative care specialists.
the intravenous prodrug of aprepitant, has demonstrated equivalent Nausea and vomiting are common side effects of chemotherapy
efficacy to the 3-day oral regimen as a single dose at 150 mg on day and should be treated aggressively to assure patient comfort during
1. Oral netupitant has been studied in HEC and MEC regimens as the treatment of their hematologic illness. A number of targeted
part of a single-dose combination product with oral palonosetron. therapies exist and should be used based on the emetogenic potential
These studies have demonstrated similar safety and efficacy of the agents used and the patient’s clinical condition and comorbidi-
when compared with combination antiemetic therapy including ties. Severe or refractory nausea should involve palliative care
aprepitant. 73 consultation.

Olanzapine
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