48 Drug Therapy With Opioids

LEARNING OBJECTIVES
After studying this chapter, you should be able to:
1 Categorize the types of pain.
2 Recognize the pathophysiology associated with pain.
3 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for the opioid agonists.
4 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for the opioid agonists/antagonists.
5 Discuss administration of preemptive analgesia in the treatment of pain related to surgery.
6 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for the opioid antagonists.
7 Understand how to implement the nursing process in the care of the patient receiving
opioid medications for pain.

Clinical Application Case Study

Darlene Homan, a 50-year-old woman, is receiving treatment for ovarian cancer. After
surgery, she arrives on the unit from the postanesthesia care unit (PACU) complaining of
lower back pain of 2 out of 10 on a 10-point pain scale. She received a total of 10 mg of
morphine sulfate in the PACU. Her vital signs are temperature 98.2F, pulse 82 beats/min,
respirations 22 breaths/min, and blood pressure 124/72 mm Hg, with an O2 saturation of
94% on 2 L/min nasal cannula.

KEY TERMS
Analgesics: drugs that relieve pain without loss of consciousness

Breakthrough pain: episodic bursts of intense pain that breaks through the pain control of the
medication regime
Ceiling eect: a phenomenon of certain drugs that limits the ability to produce a further effect above
a particular dosage level
Endogenous analgesia system: nerve signals that relieve pain by suppressing the transmission
of pain signals from peripheral nerves; can be activated by nerve signals entering the brain or by
morphine-like drugs
Endorphins: peptides (i.e., endorphins, enkephalins, and dynorphins) that interact with receptors to
inhibit perception and transmission of pain signals
Nociceptors: nerve endings that selectively respond to painful stimuli and send pain signals to the
brain and spinal cord

888

Pain: unpleasant, sensory, emotional sensation that is associated with actual or potential tissue damage
Patient-controlled analgesia: any method used by patients to administer their own pain medication, typically used to
indicate administration through a controlled intravenous pump
Preemptive analgesia: a strategy to reduce postsurgical pain by administering medications prior to the occurrence
of the noxious stimuli or pain
Introduction
Pain is an unpleasant, sensory, emotional sensation associated
with actual or potential tissue injury. The perception of pain
is part of the clinical presentation in many acute and chronic
disorders and is one of the most difcult sensations for patients
to cope with during the course of a disease. It impels a person
to remove the cause of the damage or seek relief from the pain.
This chapter aids in the understanding of drug actions by dis-
cussing pain and pain-relieving opioid drugs.
Overview of Pain
Pain is the most common symptom prompting people to
seek health care. When not managed effectively, pain may
greatly impair quality of life and ability to perform activities
of daily living. The Joint Commission includes assessment and
BOX 48.1 Types of Pain
Acute pain may result from injury, trauma, spasm, disease
processes, and treatment or diagnostic procedures that
damage body tissues. Patients often describe it as sharp
or cutting. The intensity of the pain is usually proportional
to the amount of tissue damage and the pain serves as a
warning system by demanding the suerers attention and
compelling behavior to withdraw from or avoid the pain-
producing stimulus.
Acute pain is called fast pain because it is felt quickly
after a pain stimulus is applied. It is aroused by mechani-
cal and thermal stimuli and conducted to the spinal cord
by A-delta bers in the peripheral nerves. Glutamate is the
neurotransmitter secreted in the spinal cord at the A-delta
nerve ber endings.
Acute pain is often accompanied by anxiety and objec-
tive signs of discomfort (e.g., facial expressions of distress;
moaning or crying; positioning to protect the aected part;
tenderness, edema, and skin color or temperature changes in
the aected part; and either restlessness and excessive move-
ment or limited movement, if movement increases pain).
It usually responds to treatment with analgesic drugs and
resolves as tissue repair mechanisms heal the damaged area.
Chronic (noncancer) pain (i.e., lasting 3 months
or longer) demands attention less urgently, may not be
characterized by visible signs, and is often accompanied
by emotional stress, increased irritability, depression,
social withdrawal, nancial distress, loss of libido, dis-
turbed sleep patterns, diminished appetite, weight loss,
and decreased ability to perform usual activities of daily
living. It may occur with or without evidence of tissue
CHAPTER 48 Drug Therapy With Opioids 889
management of pain for all patients (the fth vital sign) in
the standards by which it evaluates health care organizations.
Opioid analgesics are drugs that provide pain relief by affecting
peoples perception and tolerance of moderate to severe pain.
Etiology
The causes of pain include nerve damage, actual tissue injury,
cancer, or surgery. Pain may be classied according to its origin
in body structures (e.g., somatic, visceral, neuropathic), dura-
tion (e.g., acute, chronic), or cause (e.g., cancer). Box 48.1
describes these types of pain.
Pathophysiology
Pain occurs when tissue damage activates the free nerve end-
ings (pain receptors) of peripheral nerves. Nociceptors, nerve
endings that selectively respond to painful stimuli, are abun-
dant in arterial walls, joint surfaces, muscle fascia, periosteum,
damage and may include acute pain that persists beyond
the typical recovery time for the precipitating tissue injury,
pain related to a chronic disease, pain without an identi-
able cause, and pain associated with cancer. It may arise
from essentially any part of the body. It may be continuous
or episodic or a combination of both.
Chronic (noncancer) pain may also be called slow pain. It
can be elicited by mechanical, thermal, and chemical stimuli
and is described as burning, aching, or throbbing. Slow,
chronic pain is transmitted by C nerve bers to the spinal
cord and brain. Substance P is the neurotransmitter at C
nerve ber endings; it is released slowly and accumulates
over seconds or minutes.
Cancer pain has characteristics of both acute and
chronic pain, and it may be constant or intermittent.
Chronic cancer pain is often caused by tumor spread into
pain-sensitive tissues and the resulting tissue destruction.
It usually progresses as the disease advances and can be
severe and debilitating. Acute pain is often associated with
diagnostic procedures or treatment measures (e.g., surgery,
chemotherapy). It may also occur with disease progression,
with activity, or with the development of drug tolerance.
Somatic pain results from stimulation of nocicep-
tors in skin, bone, muscle, and soft tissue. It is usually
well localized and described as sharp, burning, gnawing,
throbbing, or cramping. It may be intermittent or con-
stant and acute or chronic. Sprains and other traumatic
injuries are examples of acute somatic pain; the bone and
joint pain of arthritis is an example of chronic somatic
pain, although acute exacerbations may also occur.
890 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
BOX 48.1 Types of Pain (Continued)
Somatic pain of low to moderate intensity may stimulate
the sympathetic nervous system and produce increased
blood pressure, pulse, and respiration; dilated pupils; and
increased skeletal muscle tension, such as rigid posture
or clenched sts.
Visceral pain, which is diuse and not well localized,
results when nociceptors are stimulated in abdominal or
thoracic organs and their surrounding tissues. It includes
pain associated with cholecystitis, pancreatitis, uterine
disorders, and liver disease and is often described as deep,
dull, aching, or cramping. It may be referred to a dierent
part of the body (e.g., pain from the liver can be referred to
the right shoulder area; ischemic pain from the heart can
be referred to the left arm or neck area). Severe visceral
pain stimulates the parasympathetic nervous system and
produces decreased blood pressure and pulse, nausea
and vomiting, weakness, syncope, and possibly loss of
consciousness.
skin, and soft tissues; they are scarce in most internal organs.
Causes of tissue damage may be physical (e.g., heat, cold, pres-
sure, stretch, spasm, and ischemia) or chemical (e.g., pain-
producing substances are released into the extracellular uid
surrounding the nerve bers that carry the pain signal). These
pain-producing substances activate pain receptors, increase the
sensitivity of pain receptors, or stimulate the release of inam-
matory substances.
For a person to feel pain, the signal from the nociceptors in
peripheral tissues must be transmitted to the spinal cord, then
to the hypothalamus and cerebral cortex in the brain. The
signal is carried to the spinal cord by two types of nerve cells,
A-delta bers and C bers. A-delta bers, which are myelinated or morphine-like drugs can activate the system. Important ele-
and found mainly in skin and muscle, transmit fast, sharp, well-
localized pain signals. These bers release glutamate and aspar-
tate (excitatory amino acid neurotransmitters) at synapses in
the spinal cord. C bers, which are unmyelinated and found in
muscle, abdominal viscera, and periosteum, conduct the pain
signal slowly and produce a poorly localized, dull, or burning
type of pain. Tissue damage resulting from an acute injury often
produces an initial sharp pain transmitted by A-delta bers
followed by a dull ache or burning sensation transmitted by
C bers. C bers release somatostatin and substance P at syn-
apses in the spinal cord. Glutamate, aspartate, substance P, and
perhaps other chemical mediators enhance transmission of the
pain signal.
The dorsal horn of the spinal cord is the control center or
relay station for information from the A-delta and C nerve
bers, for local modulation of the pain impulse, and for
descending inuences from higher centers in the central nerv-
ous system (CNS) (e.g., attention, emotion, memory). Here,
nociceptive nerve bers synapse with nonnociceptive nerve
bers (neurons that carry information other than pain signals).
The brain also contains descending pathways that inhibit
nociceptive input. Some brain nuclei are serotonergic and
project to the dorsal horn of the spinal cord, where they sup-
press nociceptive transmission. Another inhibitory pathway is
noradrenergic and originates in the pons. Thus, increasing the
Neuropathic pain is caused by lesions or physiologic
changes that injure peripheral pain receptors, nerves, or
the central nervous system. It is characterized by excessive
excitability in the damaged area or surrounding normal tis-
sues, so that nerve cells discharge more easily. As a result,
pain may arise spontaneously or from a normally nonpain-
ful stimulus such as a light touch. It is a relatively common
cause of chronic pain and is usually described as severe,
shooting, burning, or stabbing. It occurs with peripheral
neuropathies associated with diabetes mellitus (diabetic
neuropathy), herpes zoster infections (postherpetic neural-
gia), traumatic nerve injuries, and some types of cancer or
cancer treatments. It is dicult to treat because standard
analgesics (e.g., nonsteroidal anti-inammatory drugs and
opioids) are less eective in neuropathic pain than in other
types of pain. Antidepressants and anticonvulsants are
often used along with analgesics.
concentration of norepinephrine and serotonin in the synapse
inhibits transmission of nerve impulses that carry pain signals
to the brain and spinal cord.
In the brain, the thalamus is a relay station for incoming
sensory stimuli, including pain. Perception of pain is a primitive
awareness in the thalamus, and sensation is not well localized.
From the thalamus, pain messages are relayed to the cerebral
cortex, where they are perceived more specically and analyzed
to determine actions needed.
The CNS has its own system, the endogenous analgesia
system, for relieving pain by suppressing the transmission of pain
signals from peripheral nerves. Nerve signals entering the brain
ments include receptors and endogenous peptides with actions
similar to those of morphine. Receptors are highly concen-
trated in some regions of the CNS, including the ascending and
descending pain pathways and portions of the brain essential
to the endogenous analgesia system. The peptides (i.e., endor-
phins, enkephalins, and dynorphins) interact with receptors to
inhibit perception and transmission of pain signals. Endorphin
release can be triggered by excitement, stress, or aerobic exercise.
Enkephalins are believed to interrupt the transmission of pain
signals at the spinal cord level by inhibiting the release of sub-
stance P from C nerve bers. The endogenous analgesia system
may also inhibit pain signals at other points in the pain pathway.
Clinical Manifestations
Pain is a subjective experience, and patients self-reporting of
pain is considered the gold standard of pain assessment meas-
urements because it offers the most valid measurement of pain.
However, numerous factors, including mood, sleep distur-
bances, fatigue, and medications, may inuence self-reporting.
Cultural, gender, age, and other psychosocial factors can play a
role in manifestations of pain.
A variety of pain measurement tools exists, including visual
analogue scales, verbal or numerical rating scales, or picture
scales. The pain measurement tool chosen should be appropriate

to the individual patient, considering developmental, cognitive,
emotional, language, and cultural factors. A mnemonic device
(SOCRATES) can be used to assess the clinical manifestations
of pain. Its meaning appears below:
Site
Onset
Character
Radiation
Associations with other symptoms
Time course (pattern)
Exacerbating/relieving factors
Severity
Nurses can use observational tools for patients who cannot
communicate their pain for various reasons (e.g., unconscious-
ness, cognitive impairment). These tools involve facial expres-
sions, limb movements, vocalization, restlessness, and guarding
as indicators of pain. In patients with pain, vital signs may dem-
onstrate tachycardia, tachypnea, and hypertension.
Clinical Guidelines for the Use of
Chronic Opioid Therapy in Chronic
Noncancer Pain
by CHOU, R., FANCIULLO, G. J., FINE, P. G., ADLER,
J. A., BALLANTYNE, J. C., DAVIES, P., DONOVAN, M.
I., FISHBAIN, D. A., FOLEY, K. M., FUDIN, J., GILSON,
A. M., KELTER, A., MIASKOWSKI, C., MAUSKOP, A.,
OCONNOR, P. G., PASSIK, S. D., PASTERNAK, G. W.,
PORTENOY, R. K., RICH, B. A., ROBERTS, R. G.,
TODD, K. H.
The Journal of Pain
2009,10(2), 113130
The use of long-term opioid therapy for chronic non-
cancer pain has escalated. A systematic review of the
evidence regarding chronic opioid use for chronic can-
cer pain demonstrates that chronic opioid therapy can be
effectively and safely administered in carefully selected
and monitored patients. Clinical practice guidelines by
the American Pain Society and the American Academy
of Pain Medicine present recommendations to minimize
adverse effects and the potential for abuse of opioids.
The comprehensive recommendations provide guidance
on the myriad of issues that must be considered to ensure
patient safety while providing effective pain control.
IMPLICATIONS FOR NURSING PRACTICE: The safe and effec-
tive use of opioids in chronic noncancer pain involves
knowledge and clinical skills. Recommendations from
the clinical guidelines take into consideration the most
effective plan of care, incorporating the best available evi-
dence with clinician judgment and patient preferences to
assess and manage adverse effects, abuse, and addiction.
CHAPTER 48 Drug Therapy With Opioids 891
Drug Therapy
Opioid analgesics relieve moderate to severe pain by inhibit-
ing the transmission of pain signals from peripheral tissues to
the brain, reducing the perception of pain sensation in the
brain, producing sedation, and decreasing the emotional upsets
often associated with pain. They also inhibit the production
of pain and inammation by prostaglandins and leukotrienes
in peripheral tissues. Most of these drugs are Schedule II drugs
under federal narcotics laws and may lead to drug abuse and
dependence (see Chap. 1).
Table 48.1 outlines the subgroups of opioid analgesics: the
opioid agonists, agonists/antagonists, and antagonists. The
larger group of agonists includes morphine and morphine-like
drugs. These agents have activity at mu and kappa receptors and
thus produce prototypical effects. As their name indicates, the
agonists/antagonists have both agonist and antagonist activity.
Antagonists are antidote drugs that reverse the effects of ago-
nists. In addition, numerous combinations of opioid and nono-
pioid analgesics (see Chap. 14) are available and commonly
used in most health care settings. In addition, preemptive
analgesia is used to reduce postsurgical pain by simultaneously
administering medications from different drug classes to sup-
press pain by blocking multiple pain pathways (Box 48.2).
Opioid Agonists
Morphine sulfate, the prototype, is an opium alkaloid
used mainly to relieve moderate to severe pain. A Schedule
IIcontrolled drug, administration is most often oral or paren-
teral. Patient response depends on route of administration and
dosage.
Pharmacokinetics
Morphine is well absorbed after oral (PO), intramuscular (IM),
subcutaneous, and intravenous (IV) administration. PO formu-
lations undergo signicant rst-pass metabolism in the liver,
which means that PO doses must be larger than injected doses
to have equivalent therapeutic effects. After PO administra-
tion of fast-acting (e.g., immediate-release) formulations, peak
activity occurs in about 60 minutes. After IV injection, maxi-
mal analgesia and respiratory depression usually occur within
10 to 20 minutes. After IM injection, these effects occur in about
30 minutes. After subcutaneous injection, morphine effects
may be delayed up to 60 to 90 minutes. Morphine is extensively
metabolized in the liver, and metabolites are excreted in urine.
Morphine is about 30% bound to plasma proteins, and its half-
life is 2 to 4 hours. The duration of action is 5 to 7 hours.
Action
Morphine relieves pain by binding to receptors in the brain,
spinal cord, and peripheral tissues. When bound to the drug,
receptors function like gates that close and thereby block or
decrease transmission of pain impulses from one nerve cell to
the next. The receptors also activate the endogenous analgesia
system. The major types of receptors are mu, kappa, and delta.
892 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
TABLE 48.1
Drugs (Opioids) Administered for the Treatment of Pain
Drug Class Prototype
Agonists Morphine sulfate (MS Contin, Roxanol,
others)
Agonists/antagonists Pentazocine (Talwin)
Antagonists Naloxone (Narcan)
Most of the effects of morphine (analgesia; CNS depression,
with respiratory depression and sedation; euphoria; decreased
gastrointestinal [GI] motility; and physical dependence) are
attributed to activation of the mu receptors. Analgesia, seda-
tion, and decreased GI motility occur with activation of kappa
receptors. The endogenous analgesia system involves the delta
receptors, which may not bind with opioid drugs.
Use
The main indication for morphine is to prevent or relieve acute
or chronic pain. Specic conditions for morphine include acute
myocardial infarction, biliary colic, renal colic, burns and other
traumatic injuries, postoperative states, and cancer. Health care
providers usually give morphine for chronic pain, such as that
associated with terminal cancer, only when other measures and
BOX 48.2 Preemptive Analgesia
To lessen postsurgical pain, simultaneous administration
of medications from dierent drug classes creates a multi-
modal approach to suppress pain by blocking multiple pain
pathways. The drugs are commonly given before the start of
surgery and continue through the maintenance phase. Many
of these are considered opioid sparing, which allows a clini-
cally signicant reduction in dose of opioid during and after
surgery. This reduces opioid adverse eects without sacric-
ing the control of pain. Rather than treating pain after it has
occurred, the goal is to signicantly suppress both short- and
long-term pain. In addition, properly managed pain reduces
health care costs and improves postoperative outcome. This
therapeutic intervention is called preemptive analgesia.
Drugs that can be used in preemptive analgesia include
Ketamine, primarily used for the induction and main-
tenance of general anesthesia, usually in combination
with a sedative
Parenteral drugs include
Dexmedetomidine (Precedex) that has sedative and
hypnotic eects similar to natural sleep without respi-
ratory depression
Other Drugs in the Class
Codeine fentanyl (Actiq, Duragesic, and others)
Hydrocodone (Lortab, Vicodin)
Hydromorphone (Dilaudid)
Meperidine (Demerol)
Methadone (Dolophine)
Oxycodone (OxyContin)
Oxymorphone (Numorphan, Opana)
Tramadol (Ultram)
Butorphanol (Stadol)
Nalbuphine (Nubain)
Naltrexone (Depade, ReVia)
milder drugs are ineffective. Other clinical uses of morphine
include the following:
Before and during surgery to promote sedation, decrease
anxiety, facilitate induction of anesthesia, and decrease
the amount of anesthesia required
During labor and delivery (obstetric analgesia)
Treatment of GI disorders, such as abdominal cramping
and diarrhea
Treatment of acute pulmonary edema
Treatment of severe, unproductive cough (codeine may
be used)
Unlabeled use: relief of dyspnea associated with acute
left ventricular failure and pulmonary edema
Table 48.2 gives dosages of morphine sulfate and other opioid
agonists.
Intravenous (IV) nonsteroidal anti-inammatory drugs
(NSAIDs) such as ketorolac tromethamine (Toradol),
ibuprofen (Caldolor), and the IV form of acetamino-
phen (Ormev) for short-term management of moder-
ate to severe pain. Caution must be exercised when
administering NSAIDs (see Chap. 14) as there is an
elevated risk of postoperative bleeding.
Oral medications include
Gabapentin (Neurontin) and pregabalin (Lyrica), both
GABA analogues and anticonvulsants (Chap. 52)
Celecoxib (Celebrex), an NSAID and selective
COX-2 inhibitor
Clonidine (Catapres), a direct acting alpha-2
adrenergic receptor agonist
Neuroaxial blocks such as epidural and spinal
anesthesia, peripheral regional anesthetic techniques,
and local wound inltration using long-acting local
anesthetics to provide superior analgesia. Regional
techniques can be combined with general anesthesia
or sedation.
 CHAPTER 48 Drug Therapy With Opioids 893

TABLE 48.2
DRUGS AT A GLANCE: Opioid Agonists
Drug Pregnancy Category Routes and Dosage Ranges

Adults Children

Morphine C PO immediate release, 530 mg every 4 h IM, Sub-Q 0.050.2 mg/kg (up to
sulfate PRN 15 mg) every 4 h
(MS Contin, PO controlled release, 30 mg or more
Roxanol, others) every 812 h
IM, subcutaneously 520 mg/70 kg every
4 h PRN IV injection, 210 mg/70 kg,
diluted in 5 mL water for injection and
injected slowly, over 5 min
IV continuous infusion, 0.11 mg/mL
in 5% dextrose in water solution, by
controlled infusion pump
Epidurally, 25 mg/24 h; intrathecally,
0.21 mg/24 h
Rectal, 1020 mg every 4 h
PCA dosing based on institutional proto-
cols; standard parameters: 2 mg bolus,
1 mg dose, lockout interval 10 min, 4-h
maximum limit 30 mg, basal rate not
recommended for starting PCA
Older adult, PCA dosing per institutional
protocols typically 25% of adult dose
and requires more intense monitoring
and dose individualization
Codeine C Pain: PO, subcutaneous, IM 1560 mg 1 y or older, pain: PO, subcutaneous,
every 46 h PRN; usual dose 30 mg; IM 0.5 mg/kg every 46 h PRN
max, 360 mg/24 h 26 y, cough: PO 2.55 mg every
Cough: PO 1020 mg every 4 h PRN; 46 h; max, 30 mg/24 h
max, 120 mg/24 h 612 y, cough: PO 510 mg every
46 h; max, 60 mg/24 h
Fentanyl (Actiq, C Preanesthetic sedation: IM 0.050.1 mg Children weighing at least 10 kg:
Duragesic, 3060 min before surgery conscious sedation or preanes-
Fentora, Ionsys, Analgesic adjunct to general anesthesia: thetic sedation, 515 mcg/kg
Sublimaze)* IV total dose of 0.0020.05 mg/kg, of body weight (100400 mcg),
depending on surgical procedure depending on weight, type of
Adjunct to regional anesthesia: IM or slow procedure, and other factors; max
IV (over 12 min) 0.050.1 mg PRN dose, 400 mcg, regardless of age
Postoperative analgesia: IM 0.050.1 mg, and weight. 212 y: general anes-
repeat in 12 h if needed thesia induction and maintenance,
General anesthesia: IV 0.050.1 mg/kg IV 23 mcg/kg
with oxygen and a muscle relaxant (max
dose 0.15 mg/kg with open heart surgery,
other major surgeries, and complicated
neurologic or orthopedic procedures)
Chronic pain (Duragesic transdermal
system): 2.510 mg every 72 h
Hydrocodone (with With acetaminophen: With acetaminophen: 12 tablets 213 y or <50 kg: hydrocodone
acetaminophen: C; D, prolonged every 46 h as needed for pain, not 0.10.2 mg/kg/dose, not to
Lortab, Vicodin) use or high doses to exceed 8 tablets daily. exceed 6 doses a day or the max
(with ibupro- near term With ibuprofen: 1 tablet every 46 h recommended dose of acetami-
fen: Ibudone, With ibuprofen: C; as needed for pain, not to exceed nophen. Dosing not established
Vicoprofen) D, third trimester 5 tablets daily; consider reducing for hydrocodone with ibuprofen.
dosing in elderly Extended-release products con-
taining hydrocodone should not
894 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

TABLE 48.2
DRUGS AT A GLANCE: Opioid Agonists (Continued)
Drug Pregnancy Category Routes and Dosage Ranges

Adults Children

be given to children younger than

6 years of age and should be used
with caution in children 612 y
of age.
Hydromorphone C PO 24 mg every 46 h PRN Dosage not established
(Dilaudid) IM, subcutaneous, IV 12 mg every
46 h PRN (may be increased to 4 mg for
severe pain)
Rectal suppository
3 mg every 68 h
Meperidine C IM, IV, subcutaneous, PO 50100 mg IM, subcutaneous, PO 1.11.75 mg/
(Demerol) every 24 h kg, up to adult dose, every 34 h
Obstetric analgesia: IM, Sub-Q 50100 mg
every 24 h for three or four doses
Methadone C IM, subcutaneous, PO 2.510 mg every Not recommended
(Dolophine) 34 h PRN
Oxycodone C PO, immediate release, 5 mg every 6 h Not recommended for children
(OxyContin, PRN (OxyIR, Oxydose, OxyFAST); younger than 12 y of age
Roxicodone, 1030 mg every 4 h PRN for other
others) formulations
PO, controlled release, 10 mg every
12 h, increased if necessary
Oxymorphone C PO (Opana), 1020 mg every 46 h Dosage not established
(Numorphan, PO, extended release (Opana ER), 5 mg
Opana) every 12 h, increased by 510 mg every
12 h every 37 d until pain relieved
IM, subcutaneous 11.5 mg every 46 h
PRN
IV 0.5 mg every 46 h PRN
Rectal, 5 mg every 46 h PRN
Obstetric analgesia: IM 0.51 mg
Tramadol (Ultram) C PO 50100 mg every 46 h PRN (max, Dosage not established
400 mg/d)
Renal impairment (CrCl < 30 mL/min):
PO 50100 mg every 12 h (max dose,
200 mg/d)
Hepatic impairment (cirrhosis): PO
50 mg every 12 h
Older adults (6575 y): same as adults,
unless they also have renal or hepatic
impairment
Older adults (>75 y): <300 mg daily, in
divided doses
*
Actiq, Fentora, and Ionsys are special preparations for specic uses. (Check manufacturers instructions for dosage and administration
instructions.)

Use in Children often ignored or undertreated, including children having sur-

In general, experts do not completely understand the gical and other painful procedures for which adults routinely
physiology, pathology, assessment, and management of pain in receive an anesthetic, a strong analgesic, or both. This is espe-
children. Many authorities indicate that in children pain is cially true in preterm and full-term neonates. In the past, one

reason for inadequate prevention and management of pain
in newborns was a common belief that they did not experi-
ence pain because of immature nervous systems. However,
research indicates that neonates have abundant C bers and
that A-delta bers are developing during the rst few months
of life. These nerve bers carry pain signals from peripheral tis-
sues to the spinal cord. In addition, brain pain centers and the
endogenous analgesia system are developed and functional.
Older infants and children may experience pain even when
analgesics are readily available. For example, children may
be unable to communicate their discomfort, or they may fear
injections. Health care providers or parents may fear adverse
effects of morphine, including excessive sedation, respiratory
depression, and addiction.
To make the situation more complex, formulations of mor-
phine and other opioids for children are not generally available.
Rectal suppositories, which are used more often in children than in
adults, are useful when PO or parenteral routes are not indicated.
QSEN Safety Alert
When childrens doses are calculated based on adult
doses, fractions and decimals often result, which
greatly increases the risk of a dosage error. It is
advisable to have two people do the calculations
independently and compare results.
With all forms of opioids, it is important to note that the
effects of the drugs in children may differ from those expected
in adults because of physiologic and pharmacokinetic differ-
ences. Even with suppositories, the dose of medication received
by the child is unknown because drug absorption is erratic and
because adult suppositories are sometimes cut in half or other-
wise altered. The nurse assesses children regularly and is alert
for unusual signs and symptoms.
Use in Older Adults
It is necessary to use morphine cautiously in older adults, espe-
cially if they are debilitated; have hepatic, renal, or respira-
tory impairment; or are receiving other drugs that depress the
CNS. Older adults are especially sensitive to respiratory depres-
sion, excessive sedation, confusion, and other adverse effects.
However, they should receive adequate analgesia, along with
vigilant monitoring. Specic recommendations for use in older
adults include the following:
Start with low doses and increase doses gradually, if
necessary.
Give morphine less frequency than for younger adults
because the duration of action may be longer.
Monitor carefully for sedation or confusion. In addition,
monitor voiding and urine output because acute urinary
retention is more likely to occur in older adults.
Use in Patients With Renal Impairment
Patients with renal impairment should take minimal doses of
morphine for the shortest effective time because usual doses
may produce profound sedation and a prolonged duration of
action. Morphine produces an active metabolite that may
accumulate in patients with renal impairment.
CHAPTER 48 Drug Therapy With Opioids 895
Use in Patients With Hepatic Impairment
Morphine is extensively metabolized by the liver; therefore,
morphine may accumulate and cause increased adverse effects
in the presence of hepatic impairment. Drug accumulation and
increased adverse effects may occur if dosage is not reduced,
especially with chronic use.
Use in Patients With Critical Illness
Morphine is commonly used to manage pain associated with
disease processes and invasive diagnostic and therapeutic pro-
cedures. In intensive care units, morphine and other opioid
agonists are also used concurrently with sedatives and neuro-
muscular blocking agents, which increase the risks of adverse
drug reactions and interactions. In patients with critical illness,
morphine is usually given by IV bolus injection or continuous
infusion. Guidelines include the following:
Assume that all critically ill patients are in pain or at
high risk for development of pain.
When pain is thought to be present, identify and treat
the underlying cause when possible.
Prevent pain when possible. Some specic interventions
include being very gentle when performing nursing care
to avoid tissue trauma and positioning patients to prevent
ischemia, edema, and misalignment. In addition, give
analgesics before painful procedures, when indicated.
Consider patient-controlled analgesia (PCA), which is
any method that allows a person in pain to administer
his or her own pain relief. Commonly, an IV device regu-
lated by programmable settings delivers morphine at a
preset bolus dosage when the patient presses a button.
It is possible to program a lockout period into the pump
so that the frequency of administration is controlled, as
well as the basal amount of drug to be delivered. When
starting a continuous IV infusion of pain medication, a
health care professional gives a loading dose to attain
therapeutic blood levels quickly. The nurse assesses pain
scores after initiation, after any change in pump setting,
and periodically using a standardized pain rating scale to
assess pain relief response to the PCA medication based
on hospital protocol. Box 48.3 outlines specic assess-
ment considerations prior to and throughout the admin-
istration of opioids using PCA.
Manage pain to provide relief and prevent its recurrence.
In general, morphine should be given continuously or on a
regular schedule of intermittent doses, with supplemental
or bolus doses when needed for breakthrough pain,
episodic bursts of intense pain that break through the
pain control provided by the pain medication.
Use in Patients Receiving Home Care
The use of morphine is often restricted to a short period, and
patients self-administer their medication. The need for strong pain
medication recedes as healing occurs. The home care nurse may
teach patients and caregivers safe usage of morphine (e.g., that
the drugs decrease mental alertness and physical agility, so poten-
tially hazardous activities should be avoided). It is important to
consider nonpharmacologic methods of managing pain and ways
to prevent adverse effects of opioids, although these do not serve
896 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
BOX 48.3 Assessment for Appropriateness of Patient-Controlled Analgesia
Preprocedure cognitive assessment (patient must be
cognitively competent to actively participate in pain
management)
Assess mental status, level of consciousness, and
developmental status.
Assess patients (and familys) ability to compre-
hend teaching regarding his or her role in manag-
ing pain, specic information on pump operation,
safety measures, and when to alert a nurse.
Is the patient opioid-tolerant or opioid naive?
Opioid-tolerant: patient has been taking at least
60 mg of morphine or an equianalgesic dose of
another opioid for a week or longer.
Opioid naive: patients who do not meet opioid-
tolerant criteria and have not had narcotics in the
amounts given above for a week or more.
as a substitute for adequate pharmacologic pain relief. Physical
dependence is uncommon with short-term use of morphine for
acute pain.
With some types of chronic pain, such as those occurring
with low back pain or osteoarthritis, morphine is not indicated
for long-term use. Treatment involves nonopioid medications,
physical therapy, and other measures. The home care nurse
may need to explain the reasons for not using opioids on a long-
term basis and help patients and caregivers learn alternative
methods of relieving discomfort.
With cancer pain, the goal of treatment is to prevent or
relieve pain and keep patients comfortable, without concern
about addiction. Thus, the home care nurse must assist patients
and caregivers in understanding the appropriate use of mor-
phine in cancer care, including administration on a regular
schedule, storing the drugs to avoid use by people other than
the patient, and avoiding theft and diversion to street use. The
nurse also must be procient in using and teaching various
routes of drug administration and in arranging regimens with
potentially very large doses and various combinations of drugs.
In addition, the nurse must make an active effort to prevent
or manage adverse effects, such as a bowel program to prevent
constipation.
Additional guidelines include the following:
Morphine should be given on a regular schedule, around
the clock. Patients should be awakened, if necessary, to
prevent pain recurrence.
PO, rectal, and transdermal routes of administration are
generally preferred over injections.
When long-acting forms of morphine are given on a reg-
ular schedule, fast-acting forms also need to be available
for breakthrough pain (acute pain that occurs spontane-
ously or with activity). If supplemental or rescue doses
are needed frequently, the baseline dose of long-acting
medication may need to be increased.
In addition to morphine, other drugs may be used to
increase patient comfort (see Other Drugs in the Class).
In addition, some antidepressants and anticonvulsants
decrease neuropathic pain.
Pain assessment: use a consistent standard pain
assessment tool, such as the 0 to 10 pain scale or the
0 to 10 Faces Pain Scale for children.
Sedation assessment
Assess sedation using a consistent tool (e.g., Pas-
ero, Ramsay, or Richmond Agitation and Sedation
Scale [RASS] sedation scales).
This is a critical component; sedation precedes
respiratory depression because less opioid is
required to produce it.
Respiratory assessment
Assess rate, quality, and sounds of respirations.
Assess oxygen saturation using pulse oximetry.
Adverse Eects
Morphine has widespread pharmacologic effects, especially in
the CNS and the GI system. These effects occur with usual
doses and may be therapeutic or adverse, depending on the rea-
son for use. CNS effects include analgesia; CNS depression,
ranging from drowsiness to sleep to unconsciousness; decreased
mental and physical activity; respiratory depression; nausea
and vomiting; and pupil constriction. Sedation and respira-
tory depression are major adverse effects and potentially life-
threatening. In the GI tract, morphine slows motility, and it
may cause constipation and smooth muscle spasms in the bowel
and biliary tract.
Contraindications
Contraindications and cautions are respiratory depression,
acute or chronic lung disease, liver or kidney disease, prostatic
hypertrophy, pregnancy, increased intracranial pressure and
head injury, seizure disorders, or hypersensitivity reactions to
morphine. Lactation is a consideration (it may be safer to wait
46 hours after administration to nurse an infant). Additional
contraindications may include Addisons disease, severe
alcoholism, and toxic psychosis.
Nursing Implications
Preventing Interactions
Drugs that increase the effects of morphine are found in
Box 48.4. Naloxone is known to reverse the effects of morphine.
Herbs such as kava, valerian, and St. Johns wort may increase
the sedative effect of morphine.
Administering the Medication
Although the dose of morphine can be titrated upward for
adequate analgesia, unacceptable adverse effects (e.g., exces-
sive sedation, respiratory depression, nausea, and vomiting)
may limit the dose. With PO administration, patients may take
the drug without regard to food. However, if GI upset occurs,
food is acceptable. It is essential that PO forms are not broken

BOX 48.4 Drug Interactions:
Morphine Sulfate
Drugs That Increase the Eects of Morphine Sulfate
Alcohol
Increases sedation
Antihistamines
Increase sedation and the risk of constipation and
urinary retention
Antidepressants
Increase the risk of drowsiness, confusion, memory
loss, or respiratory distress
Antipsychotics
Increase the risk of drowsiness, confusion, memory
loss, or respiratory distress
Barbiturates
Increase the risk of drowsiness, confusion, memory
loss, or respiratory distress
Benzodiazepines
Increase the risk of drowsiness, confusion, memory
loss, or respiratory distress
Monoamine oxidase (MAO) inhibitors
Increase the risk of hypotension, respiratory depres-
sion, or coma; patients should not take morphine and
an MAO inhibitor within 14 days of each other.
Other narcotics or opiates
Increase the risk of hypotension, respiratory depres-
sion, or coma
Sedatives
Increase sedation
or crushed. The nurse dilutes and administers IV doses slowly
to minimize likelihood of adverse effects.
It is necessary to monitor respiration closely in neonates.
The antagonist naloxone should be readily available (see
Opioid Antagonists). Other guidelines for morphine admin-
istration include
Assess for pain on a regular schedule around the clock
(e.g., every 12 hours). It is important to use a consist-
ent method for assessing severity, such as a visual analog
or numeric scale. If the patient is able to communicate,
the nurse asks about the location, severity, and so forth.
If the patient is unable to communicate needs for pain
relief, as is often the case during critical illnesses, the
nurse must evaluate posture, body language, risk fac-
tors, and other possible indicators of pain.
In patients with trauma and other critical illnesses,
administer morphine by IV infusion over a prolonged
period. Health care providers may also give the drug by
transdermal patch or by epidural infusion, depending on
the patients condition. For information about the use of
PCA, see Box 48.3.
As previously stated, the nurse administers morphine by
the recommended routes (e.g., PO, IV, epidural) rather
than IM injections, because IM injections are painful
and frightening for children. For any child receiving
parenteral medications, it is essential to assess vital signs
and level of consciousness regularly.
CHAPTER 48 Drug Therapy With Opioids 897
BOX 48.5 Recognition and Management of
Toxicity With Opioid Use
Acute toxicity or overdose can occur from therapeutic
use or from abuse by drug-dependent people.
Overdose may produce severe respiratory depression
and coma.
The main goal of treatment is to restore and main-
tain adequate respiratory function.
Managed by inserting an endotracheal tube and
starting mechanical ventilation or by giving an antag-
onist, such as naloxone
Emergency supplies should be readily available in
any setting where opioids are used.
Assessing for Therapeutic Eects
The nurse assesses for decreased pain (patient reports) and gen-
eral feeling of well-being. The nurse ensures that the patient is
free from adverse effects. Tolerance (the initial dose of a sub-
stance loses its effectiveness over time) occurs with morphine
and other opioids (see Chap. 2).
Assessing for Adverse Eects
The nurse should assess for increases in respiratory distress, cardiac
rhythm disturbances, and increasing somnolence. The U.S. Food
and Drug Administration (FDA) has issued BLACK BOX
WARNINGS for all opioid analgesics because of the potentially
fatal adverse effects of respiratory depression, coma, and death, as
well as the risks of drug abuse and dependence. Assessing for pru-
ritus and urticaria, which may indicate an allergic reaction, is also
important. Sweating may be a sign of tolerance and dependence
in some patients taking morphine. Box 48.5 presents measures to
recognize and manage toxicity. Additionally, Box 48.6 measures
to recognize and manage withdrawal from opioids.
Patient Teaching
Box 48.7 presents patient teaching guidelines for morphine
sulfate and other opioids.
Clinical Application 48-1
Mrs. Homan complains of pain in her lower
back with an intensity of 7 out of 10. Her vital
signs remain stable. To manage her pain, her pre-
scriber has ordered morphine 4 to 8 mg intrave-
nously, every 2 to 4 hours as needed, to be given
over 5 minutes, as well as oxycodone 5 mg with
acetaminophen 500 mg orally (after 24 hours),
every 4 to 6 hours, as needed, not to exceed
six doses in 24 hours. When assessing pain in
Mrs. Homan, what are the major considerations?
Mrs. Homan tells the nurse that she does not
want to take morphine because she is afraid
that she will become addicted. What is the best
response regarding addiction to narcotics?
What major adverse eects of analgesics should
the nurse observe for in Mrs. Homan once the
morphine is administered?
898 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
BOX 48.6 Prevention and Management of Withdrawal With Opioid Use
Abstinence from opioids after chronic use produces
a withdrawal syndrome characterized by anxiety;
restlessness; insomnia; perspiration; pupil dilation;
piloerection (goose esh); anorexia, nausea, and
vomiting; diarrhea; elevation of body temperature,
respiratory rate, and systolic blood pressure; muscle
cramps; and dehydration.
Signs and symptoms in neonates include
tremor, restlessness, increased muscle tone,
screaming, fever, sweating, tachycardia,
vomiting, diarrhea, respiratory distress, and possibly
seizures.
Although all opioids produce similar
withdrawal syndromes, the onset, severity, and
duration vary.
With morphine, symptoms begin within a few hours
of the last dose, reach peak intensity in
36 to 72 hours, and subside over 8 to 10 days.
With methadone, symptoms begin in 1 to 2 days,
peak in about 3 days, and subside over several
weeks.
NCLEX Success
1. When caring for a patient who is receiving morphine,
it is most important that the nurse regularly assess for
which of the following?
A. respiratory depression
B. hyperactive bowel sounds
C. frequent urination
D. insomnia
2. A man has an order for morphine sulfate 2 mg intra-
venously every 2 hours following a cholecystectomy.
The patient has a history of IV drug abuse. He reports
that his pain is 7 out of 10 (with 10 being the worst)
and requests the morphine every hour. What is the
nurses appropriate response?
A. to instruct him about possible adverse effects
B. to tell him that you can administer the drug only
every 2 hours
C. to use distraction techniques to help him forget his
pain
D. to notify the surgeon of his request
Other Drugs in the Class
Several other opioid agonists aside from morphine are avail-
able (see Table 48.2). Factors such as patient variability, the
type of pain (i.e., acute vs. chronic), length of administration
of the previous drug, and drug tolerance may be inuential. To
calculate the dose of a specic opioid agonist, a prescriber may
consult an equianalgesic chart, a conversion table that lists
equivalent doses of these pain-relieving drugs. Table 48.3 out-
lines the equianalgesic dosing of common opioids.
Codeine is an opium alkaloid used for analgesic and antitus-
sive effects. This Schedule II drug produces weaker analgesic
Heroin, meperidine, methadone, morphine, oxyco-
done, and oxymorphone are associated with more
severe withdrawal symptoms than other opioids.
Ifwithdrawal
an antagonist such as naloxone (Narcan) is given,
symptoms occur rapidly and are more
intense but of shorter duration.
Recognition and treatment of early, mild symptoms
of withdrawal can prevent progression to severe
symptoms.
One technique is to give the opioid from which the
person is withdrawing, which immediately reverses
the signs and symptoms of withdrawal. Then, dos-
age is gradually reduced over several days.
Another technique is to substitute a long-acting
opioid (e.g., methadone) for a short acting.
Methadone is usually given in an adequate dose to
control symptoms, once or twice daily, and then is
gradually tapered over 5 to 10 days.
In neonates undergoing withdrawal, methadone or
paregoric may be used.
and antitussive effects and milder adverse effects than mor-
phine. Compared with other opioid analgesics, codeine is more
effective when given orally and is less likely to lead to abuse
and dependence. The injected drug is more effective than the
oral drug in relieving pain, but onset (1530 minutes), peak
(3060 minutes), and duration of action (46 hours) are about
the same. Half-life is about 3 hours. Larger doses are required
for analgesic than for antitussive effects. Codeine is often given
with acetaminophen for additive analgesic effects.
The cytochrome P450 2D6 (CYP2D6) family of enzymes
metabolizes the opioid to morphine, which is responsible for
codeines analgesic effects. As many as 10% of Caucasians,
Asians, and African Americans have inadequate amounts or
activity of the CYP2D6 enzymes and may therefore receive less
pain relief with usual therapeutic doses. Prescribers sometimes
order codeine for moderate pain, often with a nonopioid anal-
gesic. A combination of opioid and nonopioid drugs produces
additive analgesic effects and may allow smaller doses.
Fentanyl (Duragesic, Sublimaze, others) is a potent opioid
agonist that is widely used for preanesthetic medication, post-
operative analgesia, and chronic pain that requires an opioid
analgesic. Fentanyl is commonly given intravenously and may
also be given intramuscularly. In addition, other formulations
are suitable for other routes of administration. These formula-
tions are not interchangeableeach must be used appropriately.
Two transdermal formulations of fentanyl are available.
Ionsys is for short-term treatment of acute postoperative
pain in hospitalized adults who require opioid analgesics.
An adhesive skin patch, it uses a tiny electric current to
deliver a dose of fentanyl through intact skin and into
the bloodstream. The patch, which is placed on the
patients upper arm or chest, has a button the patient can
press for a preset dose of 40 mcg. Only the patient should
activate the patch (to avoid overdosing). After removal
of the Ionsys patch, serum drug levels decline gradually.

BOX 48.7 Patient Teaching Guidelines for Opioid Analgesics
General Considerations
id
For acute episodes of pain that occur at irregular inter-
vals, most opioids may be taken as needed; for acute
pain that occurs daily and for chronic pain, the drugs
should be taken on a regular schedule, around the clock.
able,
When a choice of pain-relieving medication is avail-
use the least amount of the mildest drug that is
likely to be eective in a particular situation.
Take only as prescribed. If desired eects are not
achieved, report to your health care provider. Do not
increase the dose and do not take medication more
often than prescribed. Although these principles
apply to all medications, they are especially impor-
tant with opioid analgesics because of potentially
serious adverse eects and because analgesics may
mask pain for which medical attention is needed.
drowsiness
Do not drink alcohol or take other drugs that cause
(e.g., some antihistamines, sedative-type
drugs for nervousness or anxiety, sleeping pills) while
taking opioids for pain. Combining drugs with similar
eects may lead to excessive sedation and diculty
in breathing.
when
Do not smoke, cook, drive a car, or operate machinery
drowsy or dizzy or when vision is blurred from
medication.
receiving
Sit or lie down at least 30 to 60 minutes after
an opioid by injection. Injected drugs may
cause dizziness, drowsiness, and falls when walking
around. If it is necessary to stand up, ask someone for
assistance.
Ifodshospitalized, ask a health care provider about meth-
of pain management. For example, if anticipating
surgery, ask how postoperative pain will be man-
aged, how you need to report pain and request pain
medication, and so on. It is better to take adequate
medication and be able to cough, deep breathe, and
walk around than to avoid or minimize pain medica-
tion and be unable to perform activities that promote
recovery and healing. Do not object to having bed
rails up or asking for assistance when receiving a
strong narcotic analgesic. These are safety measures
to prevent falls or other injuries because these drugs
TABLE 48.3
Equianalgesic Dosing of Common Opioids
Intravenous (IV) Dose Equianalgesic
Drug to Oral to 1 mg IV Morphine
Morphine 1:3
Oxycodone
Fentanyl patch (Duragesic) 25 mcg
Hydromorphone 1:4 0.2 mg
Methadone 1:2 Ratio increases as daily
morphine dose increases
CHAPTER 48 Drug Therapy With Opioids 899
may cause drowsiness, weakness, unsteady gait, and
blurred vision.
Avoid constipation, a common adverse eect of opioid
analgesics. It may be prevented or managed by eating
high-ber foods, such as whole-grain cereals, fruits,
and vegetables; drinking 2 to 3 quarts of uid daily;
and being as active as tolerated. If you take these
medicines for more than a few days, or if you are the
caregiver for someone who takes them, ask a health
care provider about a bowel program to prevent con-
stipation. A possible regimen is a daily stool softener
(e.g., docusate) and a daily or every other day laxative
(e.g., bisacodyl), preferably started at the same time as
the narcotic. Docusate and bisacodyl are available over
the counter.
Self-Administration
water,
Take oral opioid analgesics with 6 to 8 ounces of
with or after food to reduce nausea.
Contin, crush
Do not or chew long-acting tablets (e.g., MS
OxyContin). The tablets are formulated to
release the active drug slowly, over several hours.
Crushing or chewing causes immediate release of
the drug, with a high risk of overdose and adverse
eects, and shortens the duration of pain-relieving
eects.
You may experience these side eects: nausea, loss
of appetite (take the drug with food and lie quietly),
constipation (notify your health care provider if this
is severe; a laxative may help), dizziness, sedation,
drowsiness, and impaired visual acuity (avoid driving
or performing other tasks requiring alertness, visual
acuity).
occur,
Omit one or more doses if severe adverse eects
and report to a health care provider. Also,
report a skin rash.
Take these drugs exactly as prescribed. Avoid alcohol,
antihistamines, sedatives, tranquilizers, and
over-the-counter drugs.
disorders,
Do not take any leftover medication for other
and do not let anyone else take your
prescription.
Comments
Route: IV, subcutaneous, intramuscular, oral,
rectal, intrathecal
No IV form available in the United States.
Oxycodone: morphine 1:1 to 1:1.5
Also available in buccal and oral formulations
Sustained-release preparation available
Use only by experienced prescriber is suggested.
900 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

Duragesic is for treatment of chronic and severe malignant Oxycodone is an agonist narcotic that is used, alone or in
pain. After deposition of active drug in the skin, systemic combination with acetaminophen, for the treatment of moder-
absorption slowly occurs. Duragesic has a slow onset of ate to severe pain. Several years ago, controlled-release tablets
action (1224 hours), but it lasts about 72 hours. When (OxyContin) in 10-, 20-, 40-, and 80-mg sizes became available
a Duragesic patch is removed, the drug continues to be for extended treatment of such pain (only patients who have
absorbed from the skin deposits for 24 hours or longer. developed drug tolerance through long-term use of smaller doses
should take the 80-mg tablets). When given every 12 hours, the
With both transdermal formulations, a fast-acting formu-
tablets relieve pain around the clock. These effects are advan-
lation should be available for acute pain. An oral lozenge on
tageous to patients with terminal cancer or other chronic pain
a stick (Actiq) and a buccal tablet (Fentora) are approved
conditions. However, OxyContin soon became a popular drug of
to treat acute (breakthrough) pain in people who have been
abuse, leading to many deaths and much criminal activity. Most
receiving opioids and have become opioid-tolerant. Because of
deaths have resulted from inappropriate use (i.e., not legally pre-
a risk of respiratory depression, recommended dosages must not
scribed for the user) by chewing, crushing, and snorting through
be exceeded with any formulation.
the nose, or crushing and injecting the drug. Chewing or crush-
Hydrocodone (Lortab, Vicodin), a Schedule III drug, is
ing destroys the long-acting feature and constitutes an overdose.
similar to codeine in its analgesic and antitussive effects. It
Subsequently, the manufacturer and the FDA have issued pre-
is available only in oral combination products for cough and
cautions for prescribing OxyContin and warnings not to crush
with acetaminophen or ibuprofen for pain. Its half-life is about
the product. In addition, the FDA has approved a new formula
4 hours, and its duration of action is 4 to 6 hours. Hydrocodone
that is designed to prevent the tables from being chewed or
is metabolized to hydromorphone by the CYP2D6 enzymes.
crushed; it is hoped that this will help prevent abuse of the drug.
Hydromorphone (Dilaudid) is a semisynthetic derivative of
Oxymorphone (Numorphan, Opana) is a derivative of mor-
morphine that has the same actions, uses, contraindications,
phine with actions, uses, and adverse effects similar to those of
and adverse effects as morphine. It is more potent on a mil-
morphine. Formerly available as a solution for injection and
ligram basis and more effective orally than morphine. Effects
as a rectal suppository, prescribers ordered it infrequently. In
occur in 15 to 30 minutes, peak in 30 to 90 minutes, and last
2006, the FDA approved oral tablets (immediate-release and
4 to 5 hours. Hydromorphone is metabolized in the liver to
extended-release Opana).
inactive metabolites that are excreted through the kidneys.
Tramadol (Ultram) is an oral, synthetic, centrally active
Meperidine (Demerol) is a synthetic drug similar to morphine
analgesic for moderate to severe pain. It is effective and well
in action and adverse effects. After injection, analgesia occurs in
tolerated in older adults and in people with acute or chronic
10 to 20 minutes, peaks in 1 hour, and lasts 2 to 4 hours. After
pain, back pain, bromyalgia, osteoarthritis, and neuropathic
an oral dose, about half is metabolized in the liver and never
pain. Because it has a low potential for producing tolerance and
reaches the systemic circulation. Prescribers order meperidine
abuse, it may be used long term for the management of chronic
infrequently for therapeutic purposes, mainly because it pro-
pain. It is not chemically related to opioids and is not a controlled
duces a neurotoxic metabolite (normeperidine). Normeperidine
drug. Its mechanism of action includes binding to mu opioid
accumulates with chronic use, large doses, or renal failure and
receptors and inhibiting reuptake of norepinephrine and seroto-
produces CNS stimulation characterized by agitation, hal-
nin in the brain, actions that interfere with transmission of pain
lucinations, and seizures. The half-life of normeperidine is
signals. Analgesia occurs within 1 hour of administration and
15 to 30 hours, depending on renal function, and the effects of
peaks in 2 to 3 hours with immediate-release tablets. Tramadol
normeperidine are not reversible with opioid antagonist drugs.
causes signicantly less respiratory depression than morphine
Meperidine is not recommended for use in older adults.
but may cause other morphine-like adverse effects (e.g., drowsi-
Methadone (Dolophine) is a synthetic drug similar to mor-
ness, nausea, constipation, orthostatic hypotension).
phine but with a longer duration of action. It is usually given
Tramadol is well absorbed after oral administration, even if
orally, and onset and peak of action occur in 30 to 60 min-
taken with food. It is minimally bound to plasma proteins, and
utes. Effects last 4 to 6 hours initially and longer with repeated
its half-life is 6 to 7 hours. The CYP3A4 and CYP2D6 enzymes
use. Half-life is 15 to 30 hours, and this also lengthens with
metabolize the drug, and it forms an active metabolite. About
repeated use. Prescribers order methadone for severe pain and
30% of a dose is excreted unchanged in the urine, and 60% is
in the detoxication and maintenance treatment of opiate
excreted as metabolites. Dosage reduction in people with renal
addicts. In 2006, the FDA issued an alert about serious adverse
or hepatic impairment is necessary. Tramadol is available in
effects (e.g., death, overdose, and serious cardiac dysrhyth-
oral immediate-release tablets alone and in combination with
mias) reported in patients taking methadone. The FDA rec-
acetaminophen (Ultracet) as well as an extended-release tablet
ommended that methadone dosage for pain should be carefully
(Ultram ER) that can be given once daily.
selected and titrated and that patients should be taught not to
exceed prescribed dosage or frequency of administration.
Oxycodone (Roxicodone, others) is a derivative of codeine Opioid Agonists/Antagonists
used to relieve moderate pain; its pharmacologic actions are
similar to those of other opioid analgesics. It is a Schedule II Opioid agonists/antagonists act on the same pain receptors in
drug of abuse. With oral administration, action starts in 15 to the CNS as morphine and other opiates, resulting in interference
30 minutes, peaks in 60 minutes, and lasts 4 to 6 hours. Its half- with pain transmission and/or pain sensation. These agents have
life is unknown. It is metabolized by the CYP2D6 enzymes and agonist activity at some receptors and antagonist activity at oth-
excreted through the kidneys. ers. Because of their agonist activity, they are potent analgesics
 CHAPTER 48 Drug Therapy With Opioids 901

TABLE 48.4
DRUGS AT A GLANCE: Opioid Agonists/Antagonists
Pregnancy
Drug Category Routes and Dosage Ranges

Adults Children

Pentazocine (Talwin) C IV, 30 mg (do not exceed) every 34 h (max dose 58 y: IM 15 mg

Butorphanol (Stadol)
Nalbuphine (Nubain)
360 mg) 914 y: IM 30 mg
IM, subcutaneous, 3060 mg every 34 h (max dose
360 mg)
C IM, IV 14 mg every 34 h PRN Not recommended for children
Nasal spray 1 mg (one spray in one nostril) every younger than 18 y of age
34 h PRN
Older adults: IM 12 mg every 68 h PRN
Renal or hepatic impairment: IM 12 mg every 68 h
C IM, IV, subcutaneous 10 mg/70 kg every 36 h PRN Not recommended

with a lower abuse potential than pure agonists. However, they
are considered second-line drugs for treatment of moderate to
severe pain. Because of their antagonist activity, they should not
be given to people who have been receiving analgesics, and they
may produce withdrawal symptoms in people with dependence.
Pentazocine (Talwin) is the prototype drug of this class.
Pharmacokinetics
Pentazocine is well absorbed from the GI tract. After oral
administration, onset of signicant analgesia usually occurs in
15 to 30 minutes, and the duration of action is usually 3 hours
or longer. Concentrations in plasma coincide closely with the
onset, duration, and intensity of analgesia. One study found
that the time to mean peak concentration in 24 normal subjects
was 1.7 hours (range, 0.54 hours) after oral administration
and that the mean plasma elimination half-life was 3.6 hours
(range, 1.510 hours). Pentazocine is metabolized in the liver
and excreted primarily in the urine. The products of the oxida-
tion of the terminal methyl groups and glucuronide conjugates
are excreted by the kidney. Elimination of approximately 60%
of the total dose occurs within 24 hours. Pentazocine crosses
the placenta, and it also enters the breast milk.
Action
Pentazocine, like morphine, has sedative effect. It is a synthetic
analgesic with potency that is one third of morphine. Large doses
increase blood pressure and heart rate. It weakly antagonizes the
analgesic effects of morphine and meperidine. In addition, it
produces incomplete reversal of cardiovascular, respiratory, and
behavioral depression induced by morphine and meperidine.
Use
Pentazocine (Talwin) is used to treat moderate to severe
pain. Pentazocine (Talwin NX; a Talwin and naloxone
combination) has been shown to be benecial in managing
chronic pain. It is also used before, during, and after surgery
for short-term sedating effects. (For more information on
naloxone, see Opioid Antagonists.) Table 48.4 presents
dosage information for pentazocine and the other opioid
agonists/antagonists.
Use in Children
The safety of pentazocine has not been established in children
younger than 12 years of age. When used in children, pentazo-
cine should be prescribed by weight and in lower dosage.
Use in Older Adults
Cautious use of pentazocine is warranted in older adults because
it may lead to increased sedation, respiratory depression, and
hepatic failure. It is necessary to begin with low doses.
Use in Patients With Hepatic Impairment
Extensive liver disease, with decreased metabolism, may
predispose the patient to accentuated adverse effects. Although
laboratory tests have not indicated that pentazocine causes
or increases renal or hepatic impairment, caution is impor-
tant when administering pentazocine to patients with such
impairment.
Use in Patients With Renal Impairment
Similarly, caution is necessary in patients with renal impair-
ment. It is important to use the lowest dose possible.
Adverse Eects
The adverse effects of pentazocine are similar to those of mor-
phine (confusion, respiratory depression, and risk of dependence),
but pentazocine may be more likely to cause hallucinations. The
cardiovascular effects it may produce, which include increased
blood pressure and systemic vascular resistance, make it unsuit-
able for use in myocardial infarction.
Unlike morphine, the respiratory depressant action of pen-
tazocine is subject to a ceiling effect; this causes no further
effect (in this case respiratory depression) above a particular
902 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
dosage level. The drug can be used as an analgesic for dental
extractions except in patients dependent on opioid agonists.
Contraindications
Caution is necessary when administering pentazocine to
patients with hypothyroidism, adrenocortical insufciency,
prostate hypertrophy, inammatory or obstructive bowel
disease, acute abdominal syndromes of unknown etiology,
cholecystitis, pancreatitis, or acute alcohol intoxication and
delirium tremens. Authorities have not yet established the
safe use of pentazocine during pregnancy. However, prolonged
use of opioids during pregnancy may cause neonatal physical
dependence and withdrawal. Women should avoid taking the
drug when breast-feeding, because it may cause signs in the
infant of increased sleepiness, difculty breathing, or problems
with breast-feeding. Women should obtain medical care imme-
diately if these symptoms arise.
Nursing Implications
Preventing Interactions
The nurse should be aware that alcohol and other CNS depres-
sants add to the sedative effect of pentazocine. Concomitant
use with the phenothiazines increases the risk of respira-
tory depression, hypotension, profound sedation, or coma.
Smoking tobacco could increase the metabolic clearance rate
of pentazocine, decreasing the clinical effectiveness of a stand-
ard dose of pentazocine. Anticholinergics when used concur-
rently with opioid analgesics may result in increased risk of
urinary retention and/or severe constipation, which may lead
to paralytic ileus.
Administering the Medication
Administration of pentazocine is by IM and IV injection. Rarely,
administration is by subcutaneous injection (lactate). It is essen-
tial to give the drug at regular intervals exactly as directed.
Assessing for Therapeutic Eects
The nurse assesses for pain relief. However, tolerance can be
a problem, and it may be necessary to adjust the dosage of
pentazocine.
Assessing for Adverse Eects
The nurse assesses for respiratory depression, CNS depression,
and possible signs of withdrawal in opioid-tolerant patients.
The signs of withdrawal from pentazocine include tremors and
anxiety. The BLACK BOX WARNING issued for mor-
phine also applies to pentazocine because of its potentially fatal
adverse effects of respiratory depression, coma, and death, as
well as risks of drug abuse and dependence.
Patient Teaching
The nurse ensures that patients are instructed to notify the pre-
scriber if the pain does not disappear, becomes worse, or changes
in location or type. Patients should not stop taking pentazocine
abruptly, and they should take care when changing positions
quickly or operating equipment that requires mental alertness.
Box 48.7 outlines additional patient teaching guidelines.
Other Drugs in the Class
Butorphanol (Stadol) is a synthetic, Schedule IV agonist
similar to morphine in analgesic effects and ability to cause
respiratory depression. Prescribers order it for moderate to
severe pain. Administration may be parenteral; after IM or IV
use, analgesia peaks in 30 to 60 minutes. Alternatively, admin-
istration may be topical to nasal mucosa by a metered spray
(Stadol NS); after nasal application, analgesia peaks within
1 to 2 hours. Adverse effects include drowsiness, nausea, and
vomiting. Butorphanol is not recommended for use in children
younger than 18 years of age.
Nalbuphine (Nubain) is a synthetic analgesic used for mod-
erate to severe pain. It is not a controlled drug. Administration is
IV, IM, or subcutaneous. After IV injection, action starts in 2 to
3 minutes, peaks in 15 to 20 minutes, and lasts for 3 to 6 hours.
After IM or subcutaneous injection, action begins in less than
15 minutes, peaks in 30 to 60 minutes, and lasts for 3 to 6 hours.
The half-life is 5 hours. The most common adverse effect is
sedation; at recommended doses, other effects are minimal.
Clinical Application 48-2
Twenty-four hours after surgery, Mrs. Homan is
started on oxycodone 5 mg with acetaminophen
500 mg orally, with her pain level at 3 out of 10.
She is able to ambulate independently and is eat-
ing and voiding without diculty. In planning
for discharge, what instruction does the nurse
provide to Mrs. Homan regarding the adverse
eects of oxycodone with acetaminophen?
NCLEX Success
3. The patient receives pentazocine (Talwin) for pain.
Which of the following statements by the patient
indicates an adverse effect of the medication?
A. I feel cold all over.
B. My ears are ringing.
C. I feel like I am going to throw up.
D. My heart feels like it is skipping a beat.
4. A man is receiving patient-controlled analgesia (PCA),
and his family questions why his pain medication is
being given in this manner. The nurse is most correct
in explaining that the main advantage of PCA is that it
A. requires less nursing time
B. causes fewer adverse effects
C. relieves pain more effectively
D. can be used long term
Opioid Antagonists
An antagonist (antidote) reverses analgesia and the CNS
and respiratory depression caused by agonists. However, an
opioid antagonist does not relieve the depressant effects of
 CHAPTER 48 Drug Therapy With Opioids 903

other drugs, such as sedativehypnotic, antianxiety, and
antipsychotic agents. The chief clinical use of an antagonist is
to relieve opioid-induced CNS and respiratory depression. The
prototype of this class is naloxone (Narcan). It is essential
that this drug be readily available in all health care settings in
which opioids are given.
Pharmacokinetics
Therapeutic effects occur within minutes after IV, IM, or
subcutaneous injection and last 1 to 2 hours. Naloxone has
a shorter duration of action than opioids, and repeated injec-
tions are usually necessary. To combat the effects of a long-act-
ing drug such as methadone, patients may need injections for
2 to 3 days.
Action
Naloxone (antidote) reverses analgesia and the CNS and res-
piratory depression caused by agonists. It competes with opioids
for receptor sites in the brain and thereby prevents binding with
receptors or displaces opioids already occupying receptor sites.
When opioids cannot bind to receptor sites, they are neutral-
ized and cannot exert their effects on body cells.
Use
Naloxone has long been the drug of choice to treat respiratory
depression caused by an overdose of opioids. Given intrave-
nously, naloxone begins to reverse CNS and respiratory depres-
sion induced by opioids in minutes. Table 48.5 gives dosage
information for naloxone.
Use in Children
Cautious use of naloxone is necessary in neonates and chil-
dren. As usual, the dose is smaller and given according to kilo-
gram weight. The childs renal and hepatic function also affect
the response to the medication. The recommended route is
IV only, to control absorption.
Use in Patients With Renal Impairment
Use of naloxone in renal impairment requires caution. If it is
advised, it is necessary to give small dose. Impaired renal function
leads to slower drug excretion and increased risk of accumulation.
Use in Patients With Hepatic Impairment
Similarly, use of naloxone in hepatic impairment requires cau-
tion. It is necessary to monitor the patients liver function
closely to prevent toxicity.
Use in Patients With Critical Illness
Critically ill patients who have increased intracranial pressure,
seizure disorders, head trauma, or respiratory depression should
not receive naloxone. However, people with coma of unknown
origin may receive the drug to determine if the cause of the
mental status change could result from opioids.
Adverse Eects
Adverse effects of naloxone include tremors, drowsiness, sweat-
ing, decreased respirations, hypertension, and nausea and vom-
iting. Naloxone itself has minimal toxicity.
Contraindications
Contraindications to naloxone include known hypersensitiv-
ity to the drug, presence of narcotic abuse, and pregnancy.
The drug may precipitate withdrawal, producing tachycardia,
hypertension, and violent behavior.
Nursing Implications
Assessing for Therapeutic Eects
The nurse assesses for reversal of opioid effects, including
improved respiratory function and decreased sedation.
Assessing for Adverse Eects
The nurse assesses for decreased reparations and elevated blood
pressure. With the use of naloxone, the nurse is prepared to
repeat the dose. The return of pain is a factor to be considered.

TABLE 48.5
DRUGS AT A GLANCE: Opioid Antagonists
Pregnancy
Drug Category Routes and Dosage Ranges

Adults Children

Naloxone (Narcan)
Naltrexone (Depade, ReVia)
C Overdose: IV 0.42 mg, repeat every
23 min if needed. Give IM or
subcutaneous if unable to give IV; also
may give same dose via endotracheal tube
Postoperative reversal: IV 0.10.2 mg every
23 min until desired level of reversal is
attained
C 50 mg every 24 h; alternate dosing can be
used with supervised administration.
Birth to 5 y or weight <20 kg: 0.1 mg/kg;
may repeat every 23 min if needed
Age over 5 y or weight 20 kg or more:
2 mg/dose; may repeat every 23 min
if needed
Not approved by FDA for administration
in children

FDA, U.S. Food and Drug Administration.

904 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
Other Drugs in the Class
Naltrexone (Depade, ReVia) is an opiate antagonist that acts in
the brain to prevent opiate effects (e.g., pain relief, feelings of
well-being), making it effective in decreasing the desire to take
opiates and in treating alcohol abuse. Professionals commonly
use naltrexone as part of a complete treatment program for
substance abuse (e.g., compliance monitoring, counseling, sup-
port, behavioral contract, lifestyle modication); health care
providers administer the medication. The drug decreases the
desire to drink alcohol, and the dose is based on the patients
medical condition and response to treatment.
Contraindications to naltrexone include concurrent use of
opiates, including methadone. Such use can cause sudden with-
drawal symptoms (see Box 48.6). After discontinuing opiates,
at least 7 days should pass before a person starts taking naltrex-
one. To conrm absence of opioids, health care providers should
verify self-reporting of opioid abstinence in addicted patients
using urine analysis. If opioids are positive or there are signs
of opiate withdrawal, a naloxone challenge test (administering
small doses of naltrexone and observing for signs of withdrawal)
is typically necessary. It is important to assess liver function in
patients taking naltrexone, because liver problems may occur.
NCLEX Success
5. A man is difcult to arouse after IV administration
of morphine sulfate. He has a respiratory rate of
7 breaths/min. Which of the following is the priority
nursing diagnosis?
A. Ineffective tissue perfusion
B. Activity intolerance
C. Impaired gas exchange
D. Chronic pain
6. For an overdose of morphine sulfate, which drug
should the nurse have on hand to counteract an over-
dose?
A. phenytoin (Dilantin)
B. tramadol (Ultram)
C. naloxone (Narcan)
D. atropine sulfate (Atropine)
The Nursing Process
Assessment
The nurse must assess every patient with regard to pain,
initially to determine appropriate interventions and later to
determine whether the interventions were effective in pre-
venting or relieving pain. Although the patient is usually the
best source of data, other people may be questioned about his
or her words and behaviors that indicate pain. This is espe-
cially important with young children. During assessment,
keep in mind that acute pain may coexist with or be super-
imposed on chronic pain. Specic assessment data include
Location. Determining the location may assist in
relieving the pain or identifying its underlying cause.
Ask the patient to indicate where it hurts, if possible,
and whether the pain stays in one place or radiates to
other parts of the body.
Intensity or severity. Because pain is a subjective
experience and cannot be objectively measured, assess-
ment of severity is based on the patients description and
the nurses observations. Various scales have been devel-
oped to measure and quantify pain. These include verbal
descriptor scales in which the patient is asked to rate
pain as mild, moderate, or severe; numeric scales, with
0 representing no pain and 10 representing severe pain;
and visual analog scales, in which the patient chooses
the location indicating the level of pain on a continuum.
Assess pain in relation to time, activities, and other
signs and symptoms. Mnemonic devices, such as
SOCRATES, may be helpful.
Assess for pain on a regular schedule around the clock
(e.g., every 12 hours). Use a consistent method for
assessing severity, such as a pain scale. If the patient is
able to communicate, ask about the location, severity,
and so forth. If the patient is unable to communicate
needs for pain relief, as is often the case during critical
illnesses, evaluate posture, body language, risk factors,
and other possible indicators of pain.
Prevent pain when possible. Interventions include being
very gentle when performing nursing care to avoid tis-
sue trauma and positioning patients to prevent ischemia,
edema, and misalignment. In addition, give analgesics
before painful procedures, when indicated.
When pain occurs, manage it to provide relief and pre-
vent its recurrence. In general, morphine should be given
continuously or on a regular schedule of intermittent
doses, with supplemental or bolus doses when needed for
breakthrough pain. When starting a continuous intra-
venous (IV) infusion of pain medication, a loading dose
should be given to attain therapeutic blood levels quickly.
For uncontrolled or unexpected pain, reassess and con-
sider alternative causes for the pain.
Nursing Diagnosis
Acute pain related to tissue damage
Chronic pain related to potential tissue damage
Impaired gas exchange related to sedation and decreased
mobility
Risk for injury related to sedation and decreased mobility
Constipation related to slowed peristalsis
Decient knowledge: effects and appropriate use of opioid
analgesics
Noncompliance: drug dependence related to overuse
Planning/Goals
The patient will
Avoid or be relieved of pain
Use opioid analgesics appropriately
Avoid preventable adverse effects
Be monitored for excessive sedation and respiratory
depression
Be able to communicate and perform other activities of
daily living when feasible