Chapter 69 Approach to the Management of Cancer Pain Flashcards
KEY POINTS 1. Successful treatment of cancer pain is possible most of the time. 2. The cancer pain syndrome should be determined: nociceptive, neuropathic, or mixed. 3. Cancer pain should be assessed and managed within the dimensions of suffering that a patient and his or her family experience: physical, psychological, social, and spiritual. 4. Daily evaluation includes an assessment of the location, type, temporal profile, and severity of each significant pain. 5. The World Health Organiza
Effective pain management must begin with
comprehensive pain assessment.
the gold standard for assessing pain is
the patient’s self-report. Patients with chronic cancer pain may fail to display any signs of adrenergic stimulation such as tachycardia and hypertension even though the patient reports severe pain
Cancer pain can be classified as
nociceptive, neuropathic, or a combination of the two.
Nociceptive pain
results when pain-sensing neuronal
pathways are stimulated and function normally. Specialized receptors at the distal end of neuronal axons, termed
nociceptors, detect noxious mechanical, chemical, and thermal stimuli and generate neuronal electrical activity. These signals are transmitted normally along neuronal
pathways to the brain.
Nociceptive pain
can originate from somatic or visceral
sources, or both.
Somatic pain
originates from skin, muscle, bone, and fascia. It is mediated by the somatic nervous
system. As innervation is highly specific, localization of the pain is precise. Somatic pain is often described as sharp, aching, or throbbing.
Visceral pain
originates from internal
structures. It is mediated by the autonomic nervous system. As there is a lack of specificity of innervation, and considerable neuronal crossover, visceral pain is typically
difficult for the patient to localize or describe, and may encompass an area that is much larger than might be expected
for a single organ. Visceral pain is often characterized as crampy.
Neuropathic pain
defined as a primary lesion or dysfunction of the pain-sensing nervous system. The
lesion can be either peripheral in the somatic or visceral
nervous system, or central. The nerves themselves may be
subject to damage from compression, infiltration, ischemia, metabolic injury, or transection. The myelin sheath that insulates one nerve from another may also be damaged.
neuropathic pain may also be caused by
dysfunction of the nervous system, as in central facilitation or “wind-up” where an event that is normally not painful, such as the pressure from a bed sheet or clothing
on the chest of patient with recurrent breast cancer, causes
pain.
Neuropathic pain is often described as
burning, shooting, stabbing, or electric-like, and may be associated with numbness, tingling, and/or sensory deficits.
The temporal profile of a pain will provide further clues to
its etiology
The patient should be asked about the duration of the pain. When did it first start? How long has it
been present? Did it come on slowly, or suddenly? One can ask what the baseline or background pain is like. Does it vary over time, such as worse at night? Is the patient ever pain-free? Are there times when the pain gets much worse? What factors exacerbate or relieve the pain, such as
by activity, touch, clothing, cold/heat, procedures, and so on.
Back pain
that occurs only with weight bearing could indicate
a spinal bony metastasis.
Cancer pain is also frequently associated with
intermittent
paroxysms of pain that occur with activity (e.g., movement,
chewing, swallowing, breathing, defecating, urinating,
dressing, touch, etc.) or during a procedure.
Sequential measurement of severity using a validated severity
assessment scale will provide
an indication of the changing intensity of the pain experienced by a given patient over
time. It will also guide analgesic management. A numerical analog scale is the simplest.
numerical analog scale
The patient is
asked to indicate the severity of the pain on a 11-point scale where 0 represents “no pain” and 10 represents the
“worst possible pain.”
use to identify the relevant pathophysiology leading to a pain
state.
Together with a careful physical examination and select laboratory and imaging studies,
The concept of “total pain” emphasizes that multiple nonphysical factors can also contribute to pain, that is,
psychological factors (e.g., anxiety, depression), social factors (e.g., familial estrangement), and spiritual or existential factors (e.g., loss of meaning in life, fear of death).
use to identify the relevant pathophysiology leading to a pain
state.
Together with a careful physical examination and select laboratory and imaging studies,
World Health Organization (WHO) ladder: Step One
Acetaminophen and the nonsteroidal antiinflammatory
drugs (NSAIDs) including acetylsalicylic acid
(ASA) are the mainstay of step one of the WHO analgesic ladder for the management of mild pain
World Health Organization (WHO) ladder:Step Two
Several opioid analgesics are conventionally
available in combination with acetaminophen, ibuprofen, or ASA and are commonly used to manage moderate pain. tramadol (that has
a unique combination of weak opioid activity with other analgesic properties), meperidine, and codeine (methylmorphine, which has one-tenth the potency of morphine),
the opioids in this class are close in potency to morphine (mg for mg
The concept of “total pain” emphasizes that multiple nonphysical factors can also contribute to pain, that is,
psychological factors (e.g., anxiety, depression), social factors (e.g., familial estrangement), and spiritual or existential factors (e.g., loss of meaning in life, fear of death).
World Health Organization (WHO) three-step ladder for cancer pain
management
If the pain is mild (1/10 to 3/10), an analgesic can be chosen
from step one. If it is moderate (4/10 to 6/10), one can start with an analgesic from step two. If it is severe (7/10 to 10/10), one can start with an opioid from step three. At any step, adjuvant analgesics can be added to optimize pain
control.
World Health Organization (WHO) three-step ladder: Step One
Acetaminophen and the nonsteroidal antiinflammatory
drugs (NSAIDs) including acetylsalicylic acid
(ASA) are the mainstay of step one of the WHO analgesic ladder for the management of mild pain
World Health Organization (WHO) three-step ladder:Step Two
Several opioid analgesics are conventionally
available in combination with acetaminophen, ibuprofen, or ASA and are commonly used to manage moderate pain. tramadol (that has
a unique combination of weak opioid activity with other analgesic properties), meperidine, and codeine (methylmorphine, which has one-tenth the potency of morphine),
the opioids in this class are close in potency to morphine (mg for mg
“weak” opioids
They are used in combination, they have a ceiling to their analgesic potential due to the maximum amounts of
acetaminophen or ASA that can be administered per 24 hr (e.g., 4 g acetaminophen per 24 hr).
when a step-two drug inadequately relieves pain patients may
combine two or more medications, or take more than the prescribed amount in an attempt to obtain pain relief. In doing so they may unknowingly put themselves at increased risk for significant toxicity from either the acetaminophen or ASA component
of the medication.
World Health Organization (WHO) ladder: Step Three
The pure agonist opioid analgesics comprise
step three of the WHO analgesic ladder. Morphine is the
prototypical drug because of its ease of administration and
wide availability. Many patients with chronic pain are best managed with an appropriately titrated strong
opioid that is combined with one or more coanalgesics
World Health Organization (WHO) ladder: Step Four
should be reserved for patients whose pain is not controlled by competent use of the analgesic approaches outlined in the first three steps. In general, “step four” involves invasive approaches for pain
relief that can be summarized as follows. Subcutaneous (SC) or intravenous (IV) administration of opioid analgesics and coanalgesics may be required for patients in whom oral (PO), buccal mucosal, rectal (PR),
or transcutaneous approaches are not possible or practical,
or in whom doses of oral opioids lead to undesirable adverse effects.
Adverse effects may be minimized as a
result of
the uniform delivery of the drug parenterally, the
change in route of administration, or the reduction in firstpass
metabolite production.
Acetaminophen
it is analgesic and antipyretic, it is not anti inflammatory, at least systemically
Acetaminophen toxicity
Acetaminophen is associated with significant liver toxicity.
It is generally recommended that the total dose not exceed 4 g per 24 hr for routine dosing of patients with
normal liver function.
Cyclooxygenase (COX)
enzyme catalyzes the
conversion of arachidonic acid to prostaglandins and thromboxanes. These inflammatory mediators sensitize nerve endings to painful stimuli and stimulate a group of silent nociceptors that only fire in an inflammatory milieu. In the spinal cord, COX plays a role in setting up the dysfunctional
signaling pattern involved in neuropathic pain.
NSAIDs
potent anti-inflammatory medications that inhibit the activity of COX and decrease the levels of these inflammatory mediators. As a result, there is less
sensitization of nerve endings, less recruitment of silent
nociceptors, and less risk of central “wind-up.”
adverse effects of NSAIDs
Inhibition of COX
leads to inhibition of platelet aggregation and microarteriolar
constriction/decreased perfusion, particularly in
the stomach and kidneys. In the stomach the relative
ischemia compromises the production of gastric mucus by the chief cells, and significantly increases the risk of gastric erosions and bleeding. In the kidneys the relative
ischemia increases the risk of renal papillary necrosis and renal failure
COX exists in two forms
a constitutive form, COX-1, and a form that is inducible under conditions of inflammation, COX-2. There are both COX-2-selective and nonselective NSAIDs that target both forms of COX.
adverse effects of two forms of COX
Whereas renal insufficiency is a risk of both nonselective and COX-2-selective
NSAIDs, the risk of gastropathy and platelet inhibition is significantly decreased with COX-2-selective NSAIDs.
Patient at increased
risk for adverse effects from NSAIDs
Patients (particularly the elderly) who are dehydrated,
malnourished, cachectic, or have a history of nausea, gastritis, or gastric ulceration with NSAIDs
To minimize the risk of ischemia
the patient should
be well hydrated. The use of an H2 blocking antacid (e.g. cimetidine or ranitidine) to treat NSAID dyspepsia and
abdominal pain does not prevent gastric erosions and gastrointestinal
bleeding. Only misoprostol, a prostaglandin- E analog that reverses the effect of NSAIDs on the microarteriolar
circulation of the stomach, and the proton-pump inhibitors (such as omeprazole, pantoprazole) have been
shown to heal gastric erosions and reduce the risk of significant
gastric bleeding.
useful in patients who are thrombocytopenic
and for whom other NSAIDs are contraindicated
nonacetylated salicylates (choline magnesium trisalicylate and salsalate), nabumetone, and the COX-2 inhibitors do not significantly affect platelet aggregation.
Sulindac is thought to be least likely to induce renal failure because of
its minimal effect on prostaglandin synthesis at the level of the proximal renal tubule
In contrast to the opioids, the NSAIDs and acetaminophen
have a
ceiling effect to their analgesic potential, do
not produce pharmacologic tolerance, and are not associated with physical or psychological dependence
Opioid analgesics
act by binding to opioid receptors of three subtypes (mu, kappa, and delta) both peripherally and centrally.
most important for mediating analgesia of opioids
The central receptors in the spinal cord and
brain
opioid analgesics in common usage may be divided into
full agonists, partial agonists, and mixed agonist–antagonists. The pure agonist drugs are the most useful in chronic cancer pain.
mixed agonist–antagonist opioids
pentazocine, butorphanol, and nalbuphine
partial agonist opioids
buprenorphine
poor choices for patients with severe pain.
mixed agonist–antagonist opioids
partial agonist opioids
mixed agonist–antagonist and partial agonist opioids
vs
pure agonist opioids
They have no advantages over the pure agonist opioids. Besides having a ceiling effect to the analgesia
they produce, they have the significant disadvantage that, if combined with a pure opioid agonist, they may precipitate acute pain and opioid withdrawal symptoms
Meperidine (Demerol)
synthetic pure agonist opioid that was widely used in the postoperative management of
acute pain.
Three concerns of Meperidine (Demerol)
First, because of its short duration of action in comparison with morphine or other pure
agonist opioids, it must be dosed too frequently to provide convenient, adequate analgesia. Second, because its oral
absorption is unpredictable, a reliable oral dose cannot be
prescribed that corresponds to parenteral doses.
Third, and most significant, the major liver metabolite normeperidine, which has a longer half-life (~6 hr) than meperidine (~ 3 hr), accumulates with
repeat dosing q3h for analgesia and frequently causes significant subclinical or clinical toxicity, including impaired concentration, restlessness, agitation, excessive dreams,
hallucination, myoclonic jerks, or even seizure
route of administration is preferred for the management of cancer pain.
oral. It provides the simplest, least expensive way to manage most cancer pain. When it is not
available, analgesics can be administered buccally and rectally
before resorting to more invasive and expensive routes of delivery
time to peak serum concentration
The time to peak serum concentration (Cmax) correlates with time to peak effect, and this occurs in 1 hr for an oral or rectal dose of a short-acting opioid.
Subcutaneous doses reach peak effect in 30 min and IV doses reach peak effect in 8 min.
In a patient with severe pain, opioids should be dosed
frequently until the patient achieves pain relief or undesirable
side effects. This is accomplished by administering a single
dose and reassessing after the dose has reached peak effect
(time to Cmax: 1 hr for an oral dose, 30 min for a subcutaneous dose, and 8 min for an IV dose). If the patient remains in severe pain, the dose should be doubled and the patient observed again until peak effect.
One should distinguish between constant and intermittent pain. For constant, ongoing cancer pain, analgesics should
be prescribed
on a regular schedule at doses sufficient to
keep the pain controlled. For patients with constant pain,
dosing solely on an “as needed” or “prn” basis guarantees that the patient will frequently return to pain and may
increase both the patient’s anxiety and the total dose required to control the pain.
Dosing for constant pain
Most of the short-acting drugs used for analgesia, particularly
acetaminophen, the NSAIDs including ASA, and the opioids, follow first-order kinetics. When prescribing them on a routine schedule, they should be administered
once every half-life in order to achieve steady state and
maintain constant serum levels, such as q4h for oral opioid
dosing. Methadone, with its longer half-life, is administered
every 8 to 12 hr
When initiating, titrating, or changing analgesic therapy,
drugs that follow first-order kinetics take
5 half-lives to reach pharmacologic steady state.
Changes in dosages
should only be made once
the serum level has reached steady state, such as once every 20 to 24 hr when morphine is given PO, or even SC.
Increasing scheduled dosages before
steady state is reached may lead to
unnecessarily high
serum levels and undesired adverse effects.
Sustained-release medications
should not be used alone to adjust or titrate a patient’s uncontrolled pain. Using them
for titration unduly prolongs the process to bring the pain under control, because they can be titrated only once every 5 half-lives (roughly 60 hr). However, once the pain is controlled, changing to a sustained-release product may enhance the patient’s quality of life and improve compliance and adherence due to the decreased frequency of
dosing (e.g., q8h, q12h, q24h, etc.).
Transdermal fentanyl patches
convenient when
patients are receiving stable opioid dosing, but should not be used to titrate unrelieved pain. Approximately 12 to 18 hr are needed for significant serum levels of fentanyl to
accumulate, so appropriate doses of opioids need to be
maintained during this window of time. Fentanyl patches
may be changed every 72 hr.
If the duration and severity of the change of pain are sufficient
extra short-acting doses of the same or similar medication (breakthrough or rescue doses) on an “as needed” or “prn” basis may be appropriate.
If a patient regularly requires more than 2 to 4 breakthrough
doses per 24 hr
then the routine scheduled dose should be adjusted upwards.
For intermittent pain of short duration
(seconds to a few minutes), breakthrough dosing, particularly
of the opioids, may lead to
undesired adverse effects without increased analgesia.
Breakthrough doses of an analgesic can be given safely
with a frequency equivalent to
the time required to reach Cmax. This is 1 hr for an oral dose, 30 min for a subcutaneous
dose, and 8 min for an IV dose. Making the
patient wait any longer when the pain is not controlled simply prolongs the time required to establish optimal pain control.
The size of the breakthrough dose should be related to
the routine dose.
For the strong opioids such as morphine,
hydromorphone, and oxycodone, a simple rule-of-thumb follows: for the oral route, administer 10% of the total 24-hr dose per breakthrough dose every 1 hr as needed.
For the intravenous route, administer 50% to 100% of the hourly infusion rate every 5 to 10 min as needed. The dose is then adjusted as the routine dose changes or as the
intensity of the intermittent pain requires.
Because of Methadone long and variable half-life
care must be taken when switching from one opioid to methadone and while titrating to an effective dose. Because of its long half-life, adverse effects may appear
several days after doses are adjusted.Without continuous review these may be serious: methadone is the opioid most associated with respiratory depression when dosed on a
regular basis.
When changing between opioids, there is incomplete cross-tolerance. To correct for this when pain is controlled
reducing the dose of the new medication by 25% to 50% after calculating the equianalgesic dose
Equianalgesic Dosing
Oral Dose (mg)- Analgesic - IV/SC/IM (mg) 150 Meperidine 50 100 Codeine 60 15 Hydrocodone – 15 Morphine 5 10 Oxycodone – 4 Hydromorphone 1.5 2 Levorphanol 1 – Fentanyl 0.050
Metabolism of Opioids
Most opioids are conjugated in the liver and more than 90% of the metabolites excreted renally. Although most of the opioid metabolites are inactive, some (such as morphine 6-glucuronide) have analgesic activity and several (such as morphine 3-glucuronide) may be responsible for observed adverse effects (e.g., central nervous system excitation). Methadone and fentanyl are not renally excreted, and
fentanyl does not have active metabolites
Because of Methadone long and variable halflife
care must be taken when switching from one opioid to methadone and while titrating to an effective dose. Because of its long half-life, adverse effects may appear
several days after doses are adjusted.Without continuous review these may be serious: methadone is the opioid most associated with respiratory depression when dosed on a
regular basis.
Ketorolac 10 mg orally seems to be roughly equivalent to
the combination tablet 60 mg codeine/650 mg
acetaminophen PO or 6 to 9 mg morphine PO in cancer pain.
Transdermal fentanyl 25 mg/h is approximately
50 mg morphine PO q24h.
Metabolism of Opioids
Most opioids are conjugated in the liver and more than 90% of the metabolites excreted renally. Although most of the opioid metabolites are inactive, some (such as morphine 6-glucuronide) have analgesic activity and several (such as morphine 3-glucuronide) may be responsible for
observed adverse effects (e.g., central nervous system excitation).
Patients with severe
liver failure should have their opioid doses
decreased and/
or dosing intervals increased.
In the majority
of patients, pharmacologic tolerance develops to all of the
common adverse effects, except
constipation, within 1 to
2 weeks. they should be treated with stimulant
laxatives (e.g., senna or bisacodyl), osmotic laxatives (e.g., magnesium salts or lactulose), or prokinetic agents (e.g., metoclopramide) on a routine basis. Constipation refractory to usual laxatives can be treated with methylnaltrexone,
a peripherally acting m-opioid antagonist. Simple stool softeners (e.g., sodium docusate) are usually ineffective.
Fiber-containing products can worsen opioid-induced
constipation in patients with poor oral intake
If renal function is impaired, morphine doses should be
decreased and dosing
intervals increased. The patient with anuria may require very little or no extra morphine to maintain analgesia.
Routine dosing should be discontinued.
Adverse Effects of Opioid Analgesics
Common
Constipation Nausea/vomiting Drowsiness Dry mouth Sweats
Adverse Effects of Opioid Analgesics
Uncommon
Dysphoria/delirium Bad dreams/hallucinations Pruritus/urticaria Urinary retention Myoclonic jerks/seizures Respiratory depression
In the majority
of patients, pharmacologic tolerance develops to all of the
common adverse effects, except
constipation, within 1 to
2 weeks.
Consequently, nausea and vomiting may be
treated expectantly with
antiemetics for the short period that these symptoms are problematic. If nausea and/or vomiting persist, changing the opioid or the route of
administration may resolve the problem
patients should be counseled that the drowsiness
they experience when initiating an opioid will usually
dissipate after the first week or so. Patients can often tolerate
a little drowsiness if they are assured that it will not persist for the entire time they are taking opioid analgesics. In fact, once a stable dose of an opioid has been reached, drowsiness will likely settle completely, and function will normalize.
Persistent
somnolence may be managed by
ensuring adequate hydration and renal clearance, changing to a sustained-release
product to minimize peak effects, changing the opioid, changing the route of administration, or by adding a psychostimulant
(such as methylphenidate).
The dysphoria and confusion that occasionally occur may be managed by
ensuring adequate hydration and renal clearance (thereby minimizing metabolite
buildup), lowering the opioid dose, changing the opioid analgesic, or by adding low doses of a neuroleptic drug
such as haloperidol, chlorpromazine, or risperidone.
The pruritus and urticaria that occur with opioids are not
immune mediated, but a nonspecific release of histamine from mast cells in the skin. This may be managed with
longacting antihistamines, doxepin 10 to 30 mg PO qhs, or by changing to an alternative opioid analgesic
naloxone dose
A 0.4- or 1.0-mg ampule of naloxone can be
diluted with 10 ml of saline and 0.1 to 0.2 mg IV boluses administered every 1 to 2 min. Only if several 0.1- to 0.2-mg boluses are ineffective
should the bolus size be increased
In the setting of pain management, opioid excess presents
first as mild drowsiness, proceeds to persistent somnolence, then to a poorly arousable state, and finally to respiratory depression. These changes may be associated with
increasing restlessness, agitation, confusion, dreams, hallucinations, myoclonic jerks, or even sudden onset of
seizures.
assessing a patient for respiratory depression
remembered that a respiratory rate of 8 to
12 per minute is frequently normal. One should first check for arousability: the patient
may be sleeping. If early, or even moderate excess is present
without major compromise, the opioid can be held and normal metabolism will clear the excess opioid, particularly if the patient is adequately hydrated. Naloxone reversal is not normally necessary
opioid reversal with naloxone may be
warranted.
If the patient is not arousable, has a respiratory rate less
than 6 to 8 per minute or there is significant hypoxemia or
hypotension present
naloxone dose
A 0.4- or 1.0-mg ampule of naloxone can be
diluted with 10 ml of saline and 0.1 to 0.2 mg IV boluses administered every 1 to 2 min.
Because naloxone has a high affinity for opioid receptors, titration any faster, or with larger boluses, may precipitate
opioid withdrawal that presents as an acute
pain crisis, psychosis, or severe abdominal pain and precipitates
pulmonary edema or even myocardial infarction
Reason for short term effect of naloxone
Naloxone has a high affinity for lipids and will redistribute itself into adipose tissue within 10 to 15 min of administration. Any improvement frequently disappears within this time frame and signs of toxicity return. Repeated naloxone dosing may be necessary to sustain the reversal until the patient has cleared sufficient of the opioid to be out of danger.If the overdose is severe and considerable naloxone
is required, a continuous infusion of naloxone may be required until the crisis is over.
a patient who has been well managed on a stable dose of opioid for some time suddenly develops signs of overdose
the opioid should be stopped and sepsis, renal failure, or other causes should be ruled out. It is unlikely that the opioid alone will be the cause of the “effective overdose.”
Addiction
the psychological dependence on a drug
Physical dependence
the development of a withdrawal syndrome upon abrupt discontinuation of the drug, is not evidence of addiction. Physical dependence occurs over the same time course as tolerance develops to the adverse effects of the opioid analgesics and is the
result of changes in the numbers and function of opioid neuroreceptors in the presence of exogenous opioid.
withdrawal symptoms do not occur
If opioid analgesics are tapered instead of abruptly withdrawn. Usually the opioid dose can be reduced by 50% to 75% every 2 to
3 days without ill effect.
may be necessary to
settle the feeling of slight uneasiness or restlessness that
accompanies a rapid tapering process
a small dose of a
benzodiazepine (e.g., 0.5 to 1.0 mg of lorazepam) or of
methadone (with its longer half-life)
Adjuvant analgesics
used to enhance the analgesic efficacy
of opioids, treat concurrent symptoms that exacerbate
pain, and/or provide independent analgesia for specific types of pain.
the adjuvants
acetaminophen,
the NSAIDs, the tricyclic antidepressants, and perhaps the antiepileptics, have primary analgesic activity themselves
and may be used alone or as coanalgesics
Treatment of Bone pain from bone metastases
in part, prostaglandin mediated. Consequently, the
NSAIDs and/or corticosteroids may be particularly helpful
in combination with opioids.
Spinal cord compression
should always be considered if back pain is
severe, increasing
quickly, or associated with motor, bowel, or bladder dysfunction
Neuropathic pain
rarely controlled with opioids alone. The tricyclic antidepressants, antiepileptics, and corticosteroids
are often required in combination with the opioids to achieve adequate relief.
NSAIDs and/or acetaminophen may be added to the
opioids for adjuvant analgesia, particularly when
inflammatory
or peripheral mechanisms are thought to be responsible for the painful stimulu
Corticosteroids provide a range of effects including
anti-inflammatory activity, mood elevation, antiemetic
activity, and appetite stimulation. They reduce pain both by their anti-inflammatory effect of reducing arachidonic
acid release to form prostaglandins as well as decreasing swelling and pressure on nerve endings
Corticosteroids Undesirable effects
hyperglycemia, weight gain,
myopathy, infection, and dysphoria or psychosis may
complicate therapy.
Anticonvulsants
gabapentin, pregabalin, levetiracetam,
carbamazepine, valproate, and lamotrigine) are used either alone or in addition to opioids or other coanalgesics to manage neuropathic pain. They have been particularly advocated for neuropathic pain with a shooting or lancinating quality (such as trigeminal neuralgia or nerve root compression)
Tricyclic antidepressants
secondary amine tricyclics (nortriptyline, desipramine)
tertiary amine tricyclics (amitriptyline,
imipramine) are useful in pain management in general, and neuropathic pain in
particular. They have innate analgesic properties and are effective through mechanisms that include enhanced
inhibitory modulation of nociceptive impulses at the level of the dorsal horn.
Bisphosphonates
(such as pamidronate and zoledronate)
and calcitonin have been used as adjuvant analgesics
in the management of bone pain from bone metastases.
In cancer, bone pain is caused in large part by
osteoclast-induced bone resorption rather than the direct effects of the tumor on periosteal or medullary nerve endings
Both the bisphosphonates and calcitonin inhibit
osteoclast activity on bone and have been
reported to reduce pain significantly in at least some patients.
Neuroleptic medications
anxiolytics
Neuroleptic medications (such as haloperidol, chlorpromazine, or risperidone) and anxiolytics (such as lorazepam) are used for the management of specific psychiatric disorders that complicate pain management such as delirium, psychosis, or anxiety disorders. With the exception of methotrimeprazine and clonazepam, none have been shown to have intrinsic analgesic activity.
N-methyl-d-aspartate (NMDA) receptor antagonists
dextromethorphan, ketamine, and methadone, may
affect the spinal neural circuitry that leads to a neuropathic pain state resistant to high-dose opioids
Methadone
It exists as a racemic mix of levo and dextro isomers. The levo form
binds at opioid receptors, whereas both forms can block the NMDA receptor. It is hypothesized that its NMDA receptor
antagonist activity explains the variable potency observed
when changing from other opioids to methadone.
side effect of methadone
shown QT prolongation as a potential side effect of methadone and electrocardiogram monitoring is recommended in patients treated long term
Local anesthetics, such as systemic lidocaine
nonselective inhibitors of sodium channels have also been
utilized to treat neuropathic pain.
Topical lidocaine patches
approved for use in
postherpetic neuralgia.
clonidine
Alpha-2-adrenergic agonists. effective adjuvant analgesics for both nociceptive and
neuropathic pain.
Alpha-2-adrenergic agonists act at the level of the spinal cord
in two ways
First, they act in a mechanistically similar way to the opioids. They act on the same neurons in the cord
and lead to the same intracellular events but act through a different receptor. Thus, it is likely that they can enhance the nociceptive effects of opioids. Second, researchers believe
a-2-adrenergic agonists also decrease sympathetic outflow, which is involved with neuropathic pain.
Clonidine can be given
systemically or delivered intraspinally.
Systemic delivery may be limited by the adverse effects of
lethargy, dry mouth, and hypotension.
