Page 1662 - Hematology_ Basic Principles and Practice ( PDFDrive )

1480 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

nausea. Rarely, patients need oral or intravenous ondansetron (8 mg at bedtime and used with caution in elderly patients and in patients
taken two or three times daily). who have cardiac conduction abnormalities or bladder outlet obstruc-
tion. Combination therapy with gabapentin and nortriptyline has
been shown to be more effective than either drug alone in patients
Respiratory Depression with diabetic neuropathy and PHN. 43
Selective serotonin and norepinephrine reuptake inhibitors
Naloxone (Narcan), given intravenously, reverses opioid-induced (SSNRIs; e.g., venlafaxine and duloxetine) have been shown to be
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respiratory depression, although repeated doses are often required. analgesic for a number of neuropathic pain syndromes. There is less
Respiratory depression can occur in patients with mild-to-moderate evidence supporting the use of SSRIs for neuropathic pain.
pain during the initial use of opioids, although it is rare in patients Corticosteroids given epidurally, intravenously, or orally are useful
with severe pain and in those chronically receiving opioids. Caution as antineoplastics (e.g., in leukemia, lymphoma, and myeloma) and
should be exercised before administering naloxone to patients who can also provide nonspecific relief for patients with spinal cord
are chronically receiving opioids to avoid precipitation of severe pain compression and plexus infiltrations. Doses of 16–100 mg of dexa-
and withdrawal. In such cases, it is inadvisable to administer the usual methasone are needed to reduce vasogenic edema in spinal cord
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0.4 mg/mL dose. Rather, 0.4 mg of naloxone should be diluted with compression, but lesser doses (6–20 mg/day) can be helpful in
9 mL of saline and 1–2 mL (0.04–0.08 mg) of this dilute mixture patients with plexus injuries. Patients must be monitored for the
given every 2–3 minutes until the patient is rousable and breathing development of oral or esophageal candidiasis and steroid-induced
at least 10 times/min. Do not give enough to fully waken the patient delirium.
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or withdrawal is likely to ensue. In a comatose patient, endotracheal
tube placement is recommended to prevent aspiration from the sali-
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vation and bronchial spasm that will be induced. Naloxone should Bone Pain
not be administered to an alert patient.
Adjuvants for bone pain include NSAIDs, corticosteroids, bisphos-
phonates, receptor activator of nuclear factor κ-B ligand inhibitors
Adjuvant Analgesics (e.g., denosumab), and the radiopharmaceuticals strontium chloride
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( Sr) and samarium153-lexidronan. Multiple studies have demon-
Adjuvant analgesics are a diverse class of medications, which typically strated the efficacy of bisphosphonates in reducing skeletal complica-
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have indications for conditions other than pain. They have analgesic tions and pain from bone metastases. Pamidronate and zoledronate
properties and are often used when an opioid regimen alone is unable are recommended for patients with multiple myeloma and other
to provide sufficient analgesia or is associated with dose-limiting side hematologic malignancies with painful bone lesions. Calcium and
effects. sometimes vitamin D supplementation (especially for denosumab)
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are often needed. Also, the long-term use of bisphosphonates is
associated with a small but meaningful risk of osteonecrosis of the
Neuropathic Pain jaw. The limitations of radiopharmaceuticals include cost and
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cytopenias. Given the limited evidence available, a recent Cochrane
Adjuvant agents for patients with neuropathic pain include anticon- review did not support the use of calcitonin for control of pain from
vulsants, antidepressants, α 2 -adrenergic agonists, corticosteroids, bone metastases.
topical agents, γ-aminobutyric acid (GABA) agonists, and NMDA
RAs. 1,7,9,41 However, the analgesic antidepressants and anticonvulsants
are typically preferred for treating neuropathic pain secondary to Cannabinoids
cancer. 42
The anticonvulsants gabapentin (Neurontin) and pregabalin Long used empirically for their analgesic and antiemetic properties
(Lyrica) have the fewest side effects and are very effective for patients in a wide range of illnesses, cannabis and cannabinoid therapies have
with neuropathic pain from tumor, peripheral neuropathy from been subjected to an increasingly large number of controlled clinical
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tumor or treatment, and PHN. Despite their names, they have no trials (of varying size and quality) over the last several decades. Oral
effect on GABA receptors, but rather bind to the α-2-delta subunit cannabis, used for breakthrough pain, was studied in a recent multi-
of the N-type calcium channels in neurons within the dorsal horn, center randomized controlled trial, involving 360 patients, who were
thus inhibiting calcium influx and diminishing neuronal hyperactiv- started on a long-acting opioid. The study showed analgesic efficacy
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ity. To minimize sedation, doses should be low at first (e.g., gabapentin in the low and medium dose ranges, which were also well tolerated.
100 mg three times daily or 300 mg at bedtime; pregabalin 50 mg Inhaled cannabis, used for nausea and vomiting secondary to active
twice a day) and should be increased as tolerated every 3–5 days until cancer chemotherapy, was studied in three randomized controlled
analgesia is achieved. The effective dose of gabapentin varies between trials, involving 43 subjects in total, which demonstrated inhaled
900 and 3600 mg/day in divided doses and that of pregabalin is cannabis to be an efficacious antiemetic. Additional studies have
150–300 mg twice a day. The pharmacokinetics of gabapentin are provided evidence for its effect on spasticity, appetite stimulation, and
unique in that it has a ceiling effect related to a saturable transport insomnia.
mechanism in the gut, such that the effects of this drug may plateau
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during dose escalation. The most common dose-limiting side effect
is sedation. Gabapentin and pregabalin need to be renally dosed in SPECIFIC CLINICAL PROBLEMS
patients with decreased creatinine clearance. Peripheral edema related
to gabapentin or pregabalin may require diuretics. Pregabalin’s Oral Complications
gastrointestinal absorption is proportional to the dose throughout the
effective dose range, making titration simpler. Other, generally less Oral complications of chemotherapeutic and bone marrow trans-
effective anticonvulsants used for neuropathic adjuvants include plant regimens can be frequent causes of pain. A thorough dental
phenytoin, carbamazepine, lamotrigine, topiramate, and tiagabine. evaluation and prompt treatment of infections can minimize the
The tricyclic antidepressants (TCAs; e.g., amitriptyline, nortrip- discomfort arising from underlying periodontal disease and caries;
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tyline) are effective agents for neuropathic pain. The TCAs, when secondary bacterial, viral, and fungal infections; and mucositis.
used as adjuvant analgesics, are effective faster and at lower doses than Preventive regimens include saline, sodium bicarbonate, chlorhexi-
when they are used as antidepressants (e.g., amitriptyline is effective dine gluconate rinses, acyclovir, antifungals, and ice. Palifermin
within 2–3 days at 50–100 mg/day). However, because of their (recombinant human keratinocyte growth factor [KGF-1]) is used for
anticholinergic side effects they should be started at doses of 10–25 mg the prevention and treatment of mucositis induced by conditioning