Transcript Slide 1

Clinical Pharmacy
Chapter Nine
Pain Management
Rowa’ Al-Ramahi
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PATHOPHYSIOLOGY
• Nociceptive (acute) pain is either somatic (arising from
skin, bone, joint, muscle, or connective tissue) or visceral
(arising from internal organs such as the large intestine
or pancreas).
• Stimulation of free nerve endings known as nociceptors
is the first step leading to the sensation of pain. These
receptors are found in both somatic and visceral
structures and are activated by mechanical, thermal, and
chemical factors. Release of bradykinins, K+,
prostaglandins, histamine, leukotrienes, serotonin, and
substance P may sensitize and/or activate nociceptors.
Receptor activation leads to action potentials that are
transmitted along afferent nerve fibers to the spinal cord.
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• The body modulates pain through several processes.
The
endogenous
opiate
system
consists
of
neurotransmitters (e.g., enkephalins, dynorphins, and βendorphins) and receptors (e.g., μ, δ, κ) that are found
throughout the CNS. Endogenous opioids bind to opioid
receptors and modulate the transmission of pain
impulses.
• The CNS also contains a descending system for control
of pain transmission. This system originates in the brain
and can inhibit synaptic pain transmission at the dorsal
horn. Important neurotransmitters here include
endogenous opioids, serotonin, norepinephrine, γaminobutyric acid, and neurotensin.
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• Neuropathic and functional pain is often described in
terms of chronic pain. Neuropathic pain (e.g.,
postherpetic neuralgia, diabetic neuropathy) is a result of
nerve damage, but functional pain (e.g., fibromyalgia,
irritable bowel syndrome, tension-type headache) refers
to abnormal operation of the nervous system. Pain
circuits may rewire themselves and produce
spontaneous nerve stimulation.
• Acute pain (e.g., surgery, trauma, labor, medical
procedures) usually is nociceptive, but it can be
neuropathic. Chronic pain can be nociceptive
neuropathic/functional, or both (e.g., pain that persists
after the healing of the acute injury, pain related to a
chronic disease, pain without an identifiable cause, and
pain associated with cancer).
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TREATMENT
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NONOPIOID AGENTS
Analgesia should be initiated with the most effective
analgesic with the fewest side effects.
The nonopioids are preferred over the opioids for mild to
moderate pain. The salicylates and NSAIDs reduce
prostaglandins produced by the arachidonic acid
cascade, thereby decreasing the number of pain
impulses received by the CNS.
NSAIDs may be particularly useful for management of
cancer-related bone pain.
NSAIDs are more likely to cause GI side effects. The
salicylate salts cause fewer GI side effects than aspirin
and do not inhibit platelet aggregation.
Aspirin-like compounds should not be given to children
or teenagers with influenza or chickenpox, as Reye’s
syndrome may result.
Acetaminophen has analgesic and antipyretic activity but
little antiinflammatory action. It is highly hepatotoxic on5
overdose.
OPIOID AGENTS
• With oral opioids, the onset of action usually takes about
45 minutes, and peak effect usually is seen in about 1 to
2 hours.
• Partial agonists and antagonists compete with agonists
for opioid receptor sites and exhibit mixed agonistantagonist activity. They may have selectivity for
analgesic receptor sites and cause fewer side effects.
• In the initial stages of acute pain treatment, analgesics
should be given around the clock. As the painful state
subsides, as-needed schedules can be used. Aroundthe-clock administration is also useful for management of
chronic pain.
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• Patients with severe pain may receive very high doses of
opioids with no unwanted side effects, but as pain
subsides, patients may not tolerate even low doses.
• Most of the itching or rash reported with the opioids is
due to histamine release and mast cell degranulation,
not to a true allergic response
• When allergies occur with one opioid, a drug from a
different structural class of opioids may be tried with
caution.
For
these
purposes,
the
mixed
agonist/antagonist class behaves most like the
morphine-like agonists.
• With patient-controlled analgesia, patients selfadminister preset amounts of IV opioids via a syringe
pump electronically interfaced with a timing device; thus,
patients can balance pain control with sedation.
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• Administration of opioids directly into the CNS (epidural
and subarachnoid routes) is becoming prominent for
acute pain, chronic noncancer pain, and cancer pain.
These methods require careful monitoring because of
reports of marked sedation, respiratory depression,
pruritus, nausea, vomiting, urinary retention, and
hypotension.
• Naloxone is used to reverse respiratory depression, but
continuous infusion may be required.
• Intrathecal and epidural opioids are often administered
by continuous infusion or patient-controlled analgesia.
They are safe and effective when given simultaneously
with intrathecal or epidural local anesthetics such as
bupivacaine. All agents administered directly into the
CNS should be preservative-free.
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Major Adverse Effects of Opioid Analgesics
• Mood changes: Dysphoria, euphoria
• Somnolence: Lethargy, drowsiness, apathy, inability to
concentrate
• Stimulation of chemoreceptor trigger zone: Nausea,
vomiting
• Respiratory depression: Decreased respiratory rate
• Decreased gastrointestinal motility: Constipation
• Increase in sphincter tone: Biliary spasm, urinary
retention (varies among agents)
• Histamine release: Urticaria, pruritus, rarely exacerbation
of asthma (varies among agents)
• Tolerance: Larger doses for same effect
• Dependence: Withdrawal symptoms upon abrupt
discontinuation
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Morphine and Congeners (Phenanthrenes)
• Morphine is considered by many clinicians to be the
first-line agent for moderate to severe pain. Nausea and
vomiting are more likely in ambulatory patients and with
the initial dose.
• Respiratory depression increases progressively as
doses are increased. It often manifests as a decrease in
respiratory rate, and the cough reflex is also depressed.
Patients with underlying pulmonary dysfunction are at
risk for increased respiratory compromise. Respiratory
depression can be reversed by naloxone.
• The combination of opioid analgesics with alcohol or
other CNS depressants amplifies CNS depression and is
potentially harmful and possibly lethal.
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• Morphine produces venous and arteriolar dilation, which
may result in orthostatic hypotension. Hypovolemic
patients are more susceptible to morphine-induced
hypotension. Morphine is often considered the opioid of
choice to treat pain associated with myocardial
infarction, as it decreases myocardial oxygen demand.
• Morphine can cause constipation, spasms of the
sphincter of Oddi, urinary retention, and pruritus
(secondary to histamine release).
• In head trauma patients who are not ventilated,
morphine-induced respiratory depression can increase
intracranial pressure and cloud the neurologic
examination results.
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Meperidine and Congeners (Phenylpiperidines)
• Meperidine is less potent and has a shorter duration of
action than morphine.
• With high doses or in patients with renal failure, the
metabolite normeperidine accumulates, causing tremor,
muscle twitching, and possibly seizures. In most
settings, it offers no advantages over morphine, and it
should not be used long term. It should be avoided in the
elderly and those with renal dysfunction.
• Meperidine should not be combined with monoamine
oxidase inhibitors because of the possibility of severe
respiratory
depression
or
excitation,
delirium,
hyperpyrexia, and convulsions.
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• Fentanyl is a synthetic opioid structurally related to
meperidine. It is often used in anesthesiology as an
adjunct to general anesthesia. It is more potent and
shorter acting than meperidine. Transdermal fentanyl
can be used for treatment of chronic pain requiring
opioid analgesics. After a patch is applied, it takes 12 to
24 hours to obtain optimal analgesic effect, and
analgesia may last 72 hours. It may take 6 days after
increasing a dose before new steady-state levels are
achieved. Thus, the fentanyl patch should not be used
for acute pain. A fentanyl lozenge and a buccal dosage
form are available for treatment of breakthrough cancer
pain.
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Methadone and Congeners (Diphenylheptanes)
• Methadone has oral efficacy, extended duration of
action, and ability to suppress withdrawal symptoms in
heroin addicts. With repeated doses, the analgesic
duration of action of methadone is prolonged, but
excessive sedation may also result. Although effective
for acute pain, it is usually used for chronic cancer pain.
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Opioid Agonist–Antagonist Derivatives
• This class produces analgesia and has a ceiling effect
on respiratory depression and lower abuse potential than
morphine. However, psychotomimetic responses (e.g.,
hallucinations and dysphoria with pentazocine), a
ceiling analgesic effect, and the propensity to initiate
withdrawal in opioid-dependent patients have limited
their widespread use.
Opioid Antagonists
• Naloxone is a pure opioid antagonist that binds
competitively to opioid receptors but does not produce
an analgesic response. It is used to reverse the toxic
effects of agonist and agonist-antagonist opioids.
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Central Analgesic
• Tramadol, a centrally acting analgesic for moderate to
moderately severe pain, binds to μ opiate receptors and
weakly inhibits norepinephrine and serotonin reuptake.
• Tramadol has a side-effect profile similar to that of other
opioid analgesics. It may also enhance the risk of
seizures. It may be useful for treating chronic pain,
especially neuropathic pain, but it has little advantage
over other opioid analgesics for acute pain.
Combination Therapy
• The combination of an opioid and nonopioid oral
analgesic often results in analgesia superior to
monotherapy and may allow for lower doses of each
agent. An NSAID with a scheduled opioid dose is often
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effective for painful bone metastases.
REGIONAL ANALGESIA
• Regional analgesia with local anesthetics can provide
relief of both acute and chronic pain. Anesthetics can be
positioned by injection (i.e., in joints, in the epidural or
intrathecal space, along nerve roots) or applied topically.
• High plasma concentrations can cause CNS excitation
and depression (dizziness, tinnitus, drowsiness,
disorientation,
muscle
twitching,
seizures,
and
respiratory arrest). Cardiovascular effects include
myocardial depression and other effects. Skillful
technical application, frequent administration, and
specialized follow-up procedures are required.
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For mild pain
• Acetaminophen and/or nonsteroidal antiinflammatory
drugs when risk does not outweigh benefits.
• Always consider around-the-clock regimens.
• Use as-needed regimen for breakthrough pain or when
pain displays great variability or has greatly subsided.
• Titrate to maximum dose.
• ± Adjuvant analgesics as appropriate.
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For moderate pain
• Combination opioid and acetaminophen or nonsteroidal
antiinflammatory drugs.
• Always consider around-the-clock regimens.
• Use as-needed regimen for breakthrough pain or when
pain displays great variability or has greatly subsided.
• May use nonsteroidal antiinflammatory drugs around the
clock with an opioid as needed when risk does not
outweigh benefits.
• ± Adjuvant analgesics as appropriate.
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For severe pain
• Opioid analgesics.
• Always consider around-the-clock regimens.
• Use as-needed regimen for breakthrough pain or when
pain displays great variability or has greatly subsided.
• Use route of administration to fit needs of patient.
• Avoid excessive sedation when risk does not outweigh
benefits.
• ± Adjuvant analgesics as appropriate.
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EVALUATION OF THERAPEUTIC OUTCOMES
• Pain intensity, pain relief, and medication side effects
must be assessed on a regular basis. Postoperative pain
and acute exacerbations of cancer pain may require
hourly assessment, whereas chronic nonmalignant pain
may need only daily (or less frequent) monitoring.
• With chronic pain, monitoring tools such as the Brief
Pain Inventory, Initial Pain Assessment Inventory, or
McGill Pain Questionnaire may be useful. Quality of life
must also be assessed on a regular basis in all patients.
• The best management of opioid-induced constipation is
prevention. Patients should be counseled on proper
intake of fluids and fiber, and a laxative should be added
with chronic opioid use.
• If acute pain does not subside within the anticipated time
frame (usually 1 to 2 weeks), further investigation of the
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cause is warranted.
‫قال رسول هللا صلى هللا عليه وسلم‬
‫”ال يؤمن أحدكم حتى يحب ألخيه ما يحب لنفسه“‬
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