Chapter 69 Approach to the Management of Cancer Pain

Question 1

Effective pain management must begin with

Answer 1

comprehensive pain assessment.

Question 2

the gold standard for assessing pain is

Answer 2

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

Question 3

Cancer pain can be classified as

Answer 3

nociceptive, neuropathic, or a combination of the two.

Question 4

Nociceptive pain

Answer 4

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.

Question 5

Nociceptive pain

Answer 5

can originate from somatic or visceral

sources, or both.

Question 6

Somatic pain

Answer 6

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.

Question 7

Visceral pain

Answer 7

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.

Question 8

Neuropathic pain

Answer 8

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.

Question 9

neuropathic pain may also be caused by

Answer 9

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.

Question 10

Neuropathic pain is often described as

Answer 10

burning, shooting, stabbing, or electric-like, and may be associated with numbness, tingling, and/or sensory deficits.

Question 11

The temporal profile of a pain will provide further clues to

its etiology

Answer 11

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.

Question 12

Back pain

that occurs only with weight bearing could indicate

Answer 12

a spinal bony metastasis.

Question 13

Cancer pain is also frequently associated with

Answer 13

intermittent
paroxysms of pain that occur with activity (e.g., movement,
chewing, swallowing, breathing, defecating, urinating,
dressing, touch, etc.) or during a procedure.

Question 14

Sequential measurement of severity using a validated severity
assessment scale will provide

Answer 14

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.

Question 15

numerical analog scale

Answer 15

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.”

Question 16

use to identify the relevant pathophysiology leading to a pain
state.

Answer 16

Together with a careful physical examination and select laboratory and imaging studies,

Question 17

The concept of “total pain” emphasizes that multiple nonphysical factors can also contribute to pain, that is,

Answer 17

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).

Question 18

use to identify the relevant pathophysiology leading to a pain
state.

Answer 18

Together with a careful physical examination and select laboratory and imaging studies,

Question 19

World Health Organization (WHO) ladder: Step One

Answer 19

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

Question 20

World Health Organization (WHO) ladder:Step Two

Answer 20

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

Question 21

The concept of “total pain” emphasizes that multiple nonphysical factors can also contribute to pain, that is,

Answer 21

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).

Question 22

World Health Organization (WHO) three-step ladder for cancer pain
management

Answer 22

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.

Question 23

World Health Organization (WHO) three-step ladder: Step One

Answer 23

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

Question 24

World Health Organization (WHO) three-step ladder:Step Two

Answer 24

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

Question 25

“weak” opioids

Answer 25

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).

Question 26

when a step-two drug inadequately relieves pain patients may

Answer 26

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.

Question 27

World Health Organization (WHO) ladder: Step Three

Answer 27

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

Question 28

World Health Organization (WHO) ladder: Step Four

Answer 28

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.

Question 29

Adverse effects may be minimized as a

result of

Answer 29

the uniform delivery of the drug parenterally, the
change in route of administration, or the reduction in firstpass
metabolite production.

Question 30

Acetaminophen

Answer 30

it is analgesic and antipyretic, it is not anti inflammatory, at least systemically

Question 31

Acetaminophen toxicity

Answer 31

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.

Question 32

Cyclooxygenase (COX)

Answer 32

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.

Question 33

NSAIDs

Answer 33

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.”

Question 34

adverse effects of NSAIDs

Answer 34

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

Question 35

COX exists in two forms

Answer 35

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.

Question 36

adverse effects of two forms of COX

Answer 36

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.

Question 37

Patient at increased

risk for adverse effects from NSAIDs

Answer 37

Patients (particularly the elderly) who are dehydrated,

malnourished, cachectic, or have a history of nausea, gastritis, or gastric ulceration with NSAIDs

Question 38

To minimize the risk of ischemia

Answer 38

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.

Question 39

useful in patients who are thrombocytopenic

and for whom other NSAIDs are contraindicated

Answer 39

nonacetylated salicylates (choline magnesium trisalicylate
and salsalate), nabumetone, and the COX-2 inhibitors do not significantly affect platelet aggregation.

Question 40

Sulindac is thought to be least likely to induce renal failure because of

Answer 40

its minimal effect on prostaglandin synthesis at the level of the proximal renal tubule

Question 41

In contrast to the opioids, the NSAIDs and acetaminophen

have a

Answer 41

ceiling effect to their analgesic potential, do

not produce pharmacologic tolerance, and are not associated with physical or psychological dependence

Question 42

Opioid analgesics

Answer 42

act by binding to opioid receptors of three subtypes (mu, kappa, and delta) both peripherally and centrally.

Question 43

most important for mediating analgesia of opioids

Answer 43

The central receptors in the spinal cord and

brain

Question 44

opioid analgesics in common usage may be divided into

Answer 44

full agonists, partial agonists, and mixed agonist–antagonists. The pure agonist drugs are the most useful in chronic cancer pain.

Question 45

mixed agonist–antagonist opioids

Answer 45

pentazocine, butorphanol, and nalbuphine

Question 46

partial agonist opioids

Answer 46

buprenorphine

Question 47

poor choices for patients with severe pain.

Answer 47

mixed agonist–antagonist opioids

partial agonist opioids

Question 48

mixed agonist–antagonist and partial agonist opioids

vs

pure agonist opioids

Answer 48

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

Question 49

Meperidine (Demerol)

Answer 49

synthetic pure agonist opioid that was widely used in the postoperative management of
acute pain.

Question 50

Three concerns of Meperidine (Demerol)

Answer 50

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

Question 51

route of administration is preferred for the management of cancer pain.

Answer 51

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

Question 52

time to peak serum concentration

Answer 52

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.

Question 53

In a patient with severe pain, opioids should be dosed

Answer 53

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.

Question 54

One should distinguish between constant and intermittent pain. For constant, ongoing cancer pain, analgesics should
be prescribed

Answer 54

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.

Question 55

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

Answer 55

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

Question 56

When initiating, titrating, or changing analgesic therapy,

drugs that follow first-order kinetics take

Answer 56

5 half-lives to reach pharmacologic steady state.

Question 57

Changes in dosages

should only be made once

Answer 57

the serum level has reached steady state, such as once every 20 to 24 hr when morphine is given PO, or even SC.

Question 58

Increasing scheduled dosages before

steady state is reached may lead to

Answer 58

unnecessarily high

serum levels and undesired adverse effects.

Question 59

Sustained-release medications

Answer 59

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.).

Question 60

Transdermal fentanyl patches

Answer 60

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.

Question 61

If the duration and severity of the change of pain are sufficient

Answer 61

extra short-acting doses of the same or similar medication (breakthrough or rescue doses) on an “as needed” or “prn” basis may be appropriate.

Question 62

If a patient regularly requires more than 2 to 4 breakthrough
doses per 24 hr

Answer 62

then the routine scheduled dose should be adjusted upwards.

Question 63

For intermittent pain of short duration
(seconds to a few minutes), breakthrough dosing, particularly
of the opioids, may lead to

Answer 63

undesired adverse effects without increased analgesia.

Question 64

Breakthrough doses of an analgesic can be given safely

with a frequency equivalent to

Answer 64

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.

Question 65

The size of the breakthrough dose should be related to

the routine dose.

Answer 65

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.

Question 66

Because of Methadone long and variable half-life

Answer 66

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.

Question 67

When changing between opioids, there is incomplete cross-tolerance. To correct for this when pain is controlled

Answer 67

reducing the dose of the new medication by 25% to 50% after calculating the equianalgesic dose

Question 68

Equianalgesic Dosing

Answer 68

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

Question 69

Metabolism of Opioids

Answer 69

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

Question 70

Because of Methadone long and variable halflife

Answer 70

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.

Question 71

Ketorolac 10 mg orally seems to be roughly equivalent to

Answer 71

the combination tablet 60 mg codeine/650 mg

acetaminophen PO or 6 to 9 mg morphine PO in cancer pain.

Question 72

Transdermal fentanyl 25 mg/h is approximately

Answer 72

50 mg morphine PO q24h.

Question 73

Metabolism of Opioids

Answer 73

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).

Question 74

Patients with severe

liver failure should have their opioid doses

Answer 74

decreased and/

or dosing intervals increased.

Question 75

In the majority
of patients, pharmacologic tolerance develops to all of the
common adverse effects, except

Answer 75

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

Question 76

If renal function is impaired, morphine doses should be

Answer 76

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.

Question 77

Adverse Effects of Opioid Analgesics

Common

Answer 77

Constipation
Nausea/vomiting
Drowsiness
Dry mouth
Sweats

Question 78

Adverse Effects of Opioid Analgesics

Uncommon

Answer 78

Dysphoria/delirium
Bad dreams/hallucinations
Pruritus/urticaria
Urinary retention
Myoclonic jerks/seizures
Respiratory depression

Question 79

In the majority
of patients, pharmacologic tolerance develops to all of the
common adverse effects, except

Answer 79

constipation, within 1 to

2 weeks.

Question 80

Consequently, nausea and vomiting may be

treated expectantly with

Answer 80

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

Question 81

patients should be counseled that the drowsiness

they experience when initiating an opioid will usually

Answer 81

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.

Question 82

Persistent

somnolence may be managed by

Answer 82

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).

Question 83

The dysphoria and confusion that occasionally occur may be managed by

Answer 83

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.

Question 84

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

Answer 84

longacting antihistamines, doxepin 10 to 30 mg PO qhs, or by changing to an alternative opioid analgesic

Question 85

naloxone dose

Answer 85

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

Question 86

In the setting of pain management, opioid excess presents

Answer 86

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.

Question 87

assessing a patient for respiratory depression

Answer 87

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

Question 88

opioid reversal with naloxone may be

warranted.

Answer 88

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

Question 89

naloxone dose

Answer 89

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.

Question 90

Because naloxone has a high affinity for opioid receptors, titration any faster, or with larger boluses, may precipitate

Answer 90

opioid withdrawal that presents as an acute
pain crisis, psychosis, or severe abdominal pain and precipitates
pulmonary edema or even myocardial infarction

Question 91

Reason for short term effect of naloxone

Answer 91

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.

Question 92

a patient who has been well managed on a stable dose of opioid for some time suddenly develops signs of overdose

Answer 92

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.”

Question 93

Addiction

Answer 93

the psychological dependence on a drug

Question 94

Physical dependence

Answer 94

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.

Question 95

withdrawal symptoms do not occur

Answer 95

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.

Question 96

may be necessary to
settle the feeling of slight uneasiness or restlessness that
accompanies a rapid tapering process

Answer 96

a small dose of a
benzodiazepine (e.g., 0.5 to 1.0 mg of lorazepam) or of
methadone (with its longer half-life)

Question 97

Adjuvant analgesics

Answer 97

used to enhance the analgesic efficacy
of opioids, treat concurrent symptoms that exacerbate
pain, and/or provide independent analgesia for specific types of pain.

Question 98

the adjuvants

Answer 98

acetaminophen,
the NSAIDs, the tricyclic antidepressants, and perhaps the antiepileptics, have primary analgesic activity themselves
and may be used alone or as coanalgesics

Question 99

Treatment of Bone pain from bone metastases

Answer 99

in part, prostaglandin mediated. Consequently, the
NSAIDs and/or corticosteroids may be particularly helpful
in combination with opioids.

Question 100

Spinal cord compression

should always be considered if back pain is

Answer 100

severe, increasing

quickly, or associated with motor, bowel, or bladder dysfunction

Question 101

Neuropathic pain

Answer 101

rarely controlled with opioids alone. The tricyclic antidepressants, antiepileptics, and corticosteroids
are often required in combination with the opioids to achieve adequate relief.

Question 102

NSAIDs and/or acetaminophen may be added to the

opioids for adjuvant analgesia, particularly when

Answer 102

inflammatory

or peripheral mechanisms are thought to be responsible for the painful stimulu

Question 103

Corticosteroids provide a range of effects including

Answer 103

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

Question 104

Corticosteroids Undesirable effects

Answer 104

hyperglycemia, weight gain,
myopathy, infection, and dysphoria or psychosis may
complicate therapy.

Question 105

Anticonvulsants

Answer 105

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)

Question 106

Tricyclic antidepressants

Answer 106

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.

Question 107

Bisphosphonates

Answer 107

(such as pamidronate and zoledronate)
and calcitonin have been used as adjuvant analgesics
in the management of bone pain from bone metastases.

Question 108

In cancer, bone pain is caused in large part by

Answer 108

osteoclast-induced bone resorption rather than the direct effects of the tumor on periosteal or medullary nerve endings

Question 109

Both the bisphosphonates and calcitonin inhibit

Answer 109

osteoclast activity on bone and have been

reported to reduce pain significantly in at least some patients.

Question 110

Neuroleptic medications

anxiolytics

Answer 110

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.

Question 111

N-methyl-d-aspartate (NMDA) receptor antagonists

Answer 111

dextromethorphan, ketamine, and methadone, may

affect the spinal neural circuitry that leads to a neuropathic pain state resistant to high-dose opioids

Question 112

Methadone

Answer 112

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.

Question 113

side effect of methadone

Answer 113

shown QT prolongation as a potential side effect of methadone and electrocardiogram monitoring is recommended in patients treated long term

Question 114

Local anesthetics, such as systemic lidocaine

Answer 114

nonselective inhibitors of sodium channels have also been

utilized to treat neuropathic pain.

Question 115

Topical lidocaine patches

Answer 115

approved for use in

postherpetic neuralgia.

Question 116

clonidine

Answer 116

Alpha-2-adrenergic agonists. effective adjuvant analgesics for both nociceptive and
neuropathic pain.

Question 117

Alpha-2-adrenergic agonists act at the level of the spinal cord
in two ways

Answer 117

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.

Question 118

Clonidine can be given

Answer 118

systemically or delivered intraspinally.
Systemic delivery may be limited by the adverse effects of
lethargy, dry mouth, and hypotension.