Page 1661 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 91 Pain Management and Antiemetic Therapy in Hematologic Disorders 1479

morphine absorption over 24 hours was equivalent, whether the drug the devices also facilitate the adjustment of the continuous dose
was given orally or rectally. 9 required for pain relief.
Transdermal Route Spinal Route
The transdermal fentanyl patch delivers the lipophilic fentanyl into Epidural or intrathecal opioid infusions can be helpful for select
the fat-containing areas of the skin. The drug diffuses continuously patients. The infused opioids block pain transmission by binding to
from the patch’s reservoir through a rate-controlling membrane and receptors in the dorsal horn of the spinal cord. Because the drug is
is absorbed from the skin depot into the bloodstream, where it is being infused in close proximity to the spinal cord, only a small
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rapidly metabolized. The onset of pain relief is delayed about 12 amount of opioid is needed, and the systemic side effects are reduced.
hours, and a relatively constant plasma concentration of fentanyl is Problems with this delivery system in patients who are not opioid
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not reached until about 14–20 hours after the initial patch is placed. naive include pruritus, respiratory depression, and sedation. If toler-
Liberal rescue medication must therefore be provided during the first ance to the opioid develops and higher doses are required for relief,
24 hours of use of the patch. Similarly if a patient develops signs of the incidence of side effects may approach that of systemically
fentanyl overdose, naloxone (Narcan) must be given until the skin administered opioids. 38,39 Addition of local anesthetic or α-adrenergic
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reservoir has become depleted. About 50% of the drug is still present agent (e.g., clonidine) or other agents to the epidural opioid infu-
24 hours after patch removal. Converting patients from oral or par- sion allows for fairly rapid lowering of the opioid concentration and
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enteral medication to the patch is easily accomplished (see box on reestablishing opioid sensitivity but can cause hypotension. 40
Relative Potencies of Commonly Used Opioids). A new patch is
applied every 72 hours, although up to 25% of patients require a new
patch every 48 hours. Management of Opioid-Related Side Effects
The transdermal system is an effective method of delivering pain
relief for patients with a stable level of chronic moderate-to-severe Sedation
pain, no oral route available, or no desire to take pills. Side effects
include those caused by the contact adhesive along with those com- The addition of 2.5–7.5 mg of dextroamphetamine or methylpheni-
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monly associated with other opioids, but they may be better tolerated date (taken orally twice daily) has been shown to reduce opioid-
than those caused by morphine. induced sedation and at times allow for escalation of opioid doses
The transdermal system should not be used in patients with sepsis, without sedation. These medications also improve cognitive function
those experiencing acute pain, those with markedly fluctuating opioid and symptoms of depression. Methylphenidate may also enhance the
9
requirements, cachectic patients, or individuals with significant der- analgesic effects of opioids. They should be avoided in patients with
matologic insults (i.e., skin graft-versus-host disease [GVHD] or anxiety, moderate-to-severe hypertension, agitation, thyrotoxicosis,
diffuse varicella). When the patient’s temperature rises to 40°C, drug tachyarrhythmias, severe angina pectoris, and closed-angle glaucoma.
absorption from the skin can increase by as much as 35%. If hepatic Modafinil (Provigil), a novel psychostimulant with a mechanism of
function is impaired or sepsis or shock develops and blood flow to action different than the amphetamine derivatives, which is approved
the liver decreases, plasma concentrations may rise sharply. Patients for narcolepsy and fatigue related to multiple sclerosis, has also been
with cachexia lack the subcutaneous tissue necessary for formation of found to be effective for opioid-related sedation. 9
a drug reservoir. Lower doses may also be required in elderly patients
and in those with respiratory insufficiency.
Transdermal buprenorphine (Butrans) patches have been shown Constipation
36
to be safe and effective in patients with cancer pain. They can be
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used alone or in combination with other opioids without reported Constipation is the most common opioid-induced side effect. Laxa-
problems, and unlike other opioids, which can cause a hyperalgesia tives should therefore be given routinely, not on an as-needed (PRN)
effect from long-term use, buprenorphine has been described to basis, 1,7,9 to patients treated with any of the drugs listed in the box
exert an antihyperalgesic effect. A lack of immunosuppression and on Relative Potencies of Commonly Used Opioids. Detailed bowel
safety in renal insuffiency make buprenorphine ideal for the treat- preparation recommendations can be found, but no regimen has been
ment of cancer patients. Due to the risk of QTc prolongation the studied in a controlled fashion. Commonly used stool softeners and
transdermal patch carries an FDA warning against exceeding 20 µg stimulants include docusate sodium, senna, lactulose, and polyethyl-
per hour. ene glycol. A combination of a stool softener and laxative seems to
be a rational choice for patients taking chronic opioids (e.g., docusate
Transmucosal Route sodium with senna). Promotility agents most directly counter the
Transmucosally administered fentanyl induces rapid analgesia with a mechanism of opioid-induced constipation. Bulk-forming laxatives
short duration of effect (≈1 hour) and is an effective treatment in the such as psyllium and methylcellulose should be avoided because they
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management of breakthrough pain. Oral transmucosal fentanyl increase stool volume without promoting peristaltic action. For
citrate (Actiq), fentanyl buccal tablet (Fentora), fentanyl buccal refractory opioid-induced constipation, a trial of oral naloxone,
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soluble film (Onsolis), and fentanyl sublingual tablets (Abstral), as methylnaltrexone, or alvimopan may be initiated. These µ-opioid
well as a fentanyl nasal spray (Lazanda) are the available transmucosal receptor antagonists (RAs) act locally to reverse the effects of opioids
fentanyl products. They have been found to be both efficacious and on the gut. There is minimal systemic absorption with oral naloxone
safe in the treatment of cancer-related breakthrough pain. and subsequently a low risk of precipitating opioid withdrawal or
worsening pain at low-to-moderate doses (1.6–12 mg/day). Methyln-
Subcutaneous and Intravenous Routes altrexone (administered subcutaneously) and alvimopan (oral) do
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Subcutaneous or intravenous administration of opioids can provide not cross the blood–brain barrier and therefore do not cause opioid
pain relief in the shortest amount of time with minimal oversedation. withdrawal or worsening pain.
The drugs can be delivered by portable infusion pump that is initiated
9
or continued in the home. Guidelines for their use are available. PCA
systems for subcutaneous or intravenous drug delivery have the Nausea
advantage of responding to the individual patient’s threshold for pain
while eliminating delays when nurses must administer supplemental Prochlorperazine (10 mg taken two or three times daily) or metoclo-
medication. The pumps can administer a continuous fixed infusion pramide (10 mg taken three to four times daily) can prevent the
of the opioid chosen and allow the patient to self-administer boluses nausea that occurs in most patients during the first days of opioid
of additional medication at frequencies chosen by the physician. By therapy. Relieving constipation or changing the opioid (e.g., from
recording the additional amounts of self-administered medication, morphine to oxycodone) often eliminates the later development of