Transcript Pain - UW Canvas

Pain and Pain Management
NURS 310 Winter 2016
http://www.americanpainsociety.org/
Lecture Outline
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What is pain?
Common Misconceptions about Pain
Consequences of Undertreated Pain
Pain Pathways
Classifications/ Terminology related to Types of Pain
• Basic Approach to Pain Management
• Non-opioid analgesics
– Cyclo-oxygenase inhibitors
– Adjuvant Analgesics
• Opioid medications
– Therapy for pain, physical dependence
– Diversion, Abuse, Addiction
• Non-pharmacological Interventions and other modalities
• Management of cancer pain
What is pain?
Pain
• Definition “An unpleasant sensory and emotional
experience associated with actual or potential tissue
damage, or described in terms of such damage”
– International Association for the Study of Pain
• The experience of pain includes emotional responses
• Response to pain may also have a cognitive component
in addition to the sensation and emotional experience of pain:
the meaning, context, and other psychosocial factors may
further impact the experience of pain
• A person does not need to be conscious to experience pain
• Patient’s description of his/her pain is the cornerstone of pain
assessment
Pain, cont’d
• Pain is a very personal and subjective experience:
– With a sensory/ discriminative component
(where is it, what does it feel like)
– An affective component (emotion)
– And may also have a cognitive component
(context of the experience)
• Pain is “whatever the patient says it is, whenever he
says he has it”…
• Pain is always subjective to the patient’s report
Common
misconceptions
Common Misconceptions about Pain
• The caregiver is the best judge of pain.
• A person with pain will have obvious signs such as facial
grimaces/moaning/crying or abnormal vital signs.
• A person in pain will not do normal activities of daily living.
• Pain is a normal part of aging.
• Addiction is common when opioid medications are prescribed.
• Morphine and other strong pain relievers should be reserved for
the late stages of dying.
• Morphine and other opioids can easily cause lethal respiratory
depression.
• Many people claim to be in pain because they want to get
“high.”
Consequences
of undertreated
pain
Consequences of Untreated Pain
-if pain isn’t properly treated
Pain can have a cascade of negative consequences to the patient,
who may:
• Withdraw from usually meaningful and enjoyable activities
• Develop sadness, anxiety, irritability, depression, hopelessness,
despair
• Develop personality changes, eg physical or verbal aggression,
wandering, acting-out, uncooperative/ resisting care, complain,
irritable (common changes seen in LTC pts with inadequately
managed pain)
• Have difficulty sleeping, sitting, walking, changing position,
rolling over in bed, transferring
• Difficulty maintaining appearances, performing routine hygiene,
may become bed bound
• appetite or weight changes
• Physiologic changes may lead to development of pain
syndromes
Undertreated
pain can also
affect loved
ones, family,
hospital staff
and cost of
care
Physiologic Responses to Pain
• Sympathetic nervous system activation during acute pain can
lead to:
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Increased heart rate, respirations, blood pressure
Dilated pupils
Perspiration
Pallor
Increased circulating blood glucose
Decreased gastrointestinal motility
Hypomotility of the bladder
• May be physiologically helpful in the short term but becomes
deleterious if excessive or prolonged
• Eventually, physiologic adaptation occurs and the observed
sympathetic response to pain abates
• Chronic pain may arise as a maladaptation from dysfunctional
resolution of acute pain
Pain pathways
simplified
A few terms
• Analgesia- absence of pain (due to drug effect) in response to
stimulation which would normally be painful
• Nociceptor- a sensory receptor of the peripheral (somatosensory)
nervous system that transmits AP (action potential) re: presence
of noxious stimuli to the brain
• Nociceptive fiber- a neuron with nociceptors; transmits “pain
messages”
• Noxious stimuli- a stimulus that is damaging, or threatens to
damage, normal tissue (chemical, mechanical, thermal); activates
nociceptors (“noci-receptors”) on nociceptive neurons
• Pain threshold- the minimum intensity of a stimulus that is
perceived to be painful
• Narcotic is considered an out-dated term- but still very widely
used
Step 1: transduction initiates “pain message”
along an afferent nociceptive pain fiber
Cyclooxygenase
Damaged cell membranes
Arachidonic acid → → → → prostanoids and
related compounds
1- Transduction of stimuli
↓
2- Transmission of afferent AP
↓
3- Perception of pain
↓
4-
↓
Such as inhibition of afferent
input (as shown on previous
slide) OR competitive
inhibition of afferent impulses
posed by peripheral cells
(gate-control theory)
Rub hand
Classifications of
pain
- Physiologic vs Pathologic Pain
- Duration of time that pain has persisted
- Type of affected tissue in the body
- Etiology- disease, infection, trauma
• Physiologic pain- tissue injury has occurred
• Protective message! Promotes survival!
• Pathologic pain- develops after tissue injury,
but as a consequence of persistent changes within
the peripheral and central nervous systems
− Pain can be significantly enhanced (hyperalgesia)
− Non-noxious stimuli may cause pain (allodynia)
− These changes serve no beneficial purpose
Acute Pain
• Acute pain is a normal sensation that warns of tissue injury;
results from noxious stimuli that activates nociceptors
• Self-limited: acute pain resolves over days/weeks when
the injury heals. May persist up to 3 months.
• Not necessarily more severe than chronic
• May be sudden onset or slow in onset
• Examples: traumatic injuries, post-operative pain, tissue damage
(such as strep throat or sun burn), and inflammatory processes
(such as pain after over-exertion/ over-use)
• Clinical manifestations: if severe, elevated HR, RR, BP;
pallor, sweating, and nausea; Pacing, grimacing, crying,
or moaning, waking from sleep.
• Treatment is short-term and curative
• Medications: Short-term therapy with non-opioid and/or opioid
medications to provide adequate pain relief
*may prevent some types of chronic pain
• Risk of becoming dependent on drugs is minimal
Chronic Pain
• Often defined as any pain lasting more than 3 months
– MAY arise after an acute injury/ illness
– MAY be associated with a known or unknown disease process
– MAY arise from psychological stressor(s)
• It is often difficult or impossible to identify a specific cause
• Considered by many to be a “state of disease.”
• Chronic pain appears to serve no useful purpose, has no predictable ending,
often can’t be cured, and is commonly undertreated
• Presumed neural alterations in CP include:
– Peripheral: Increased peripheral transduction sensitivity
– Central: sensitization causes abnormal state of responsiveness or
increased “gain” of nociceptive inputs
• Clinical manifestations: generally not associated with signs and symptoms of
sympathetic activity (no changes in vital signs). Often has a cascade of
consequences, +/- psychosocial indicators, such as: irritability, social
withdrawal, job loss, poor housekeeping or yard care, decreased hygiene,
substance use, weight changes, and so on. Depression common.
• Treatment: Goal-oriented, to promote functionality and QOL.
Multidisciplinary approach. Pain clinic with multimodal therapies.
Meds are only PART of necessary therapy. Several specific guidelines. (APS)
Classification of pain based on affected tissue
Classification of pain based on affected tissue:
Nociceptive Pain (i.e. somatic and visceral pain)
Associated with tissue injury (inflammation)
Somatic pain – caused by injury to skin, muscles, bones, joints,
and connective tissues.
 localized;
 nerve endings respond to temperature, vibration, swelling
 often sharper quality
Visceral pain – caused by problems with internal organs
 vague, poorly localized, pressure-like, deep squeezing, dull or
diffuse aching
Medications for nociceptive pain (i.e. somatic and visceral pain)
 Responds to non-opioids (i.e. cyclo-oxygenase inhibitors)
 Responds well to opioid analgesics
Classification of pain based on affected tissue
Neuropathic Pain
• Caused by tissue injury (trauma, disease, infection, or medicationinduced) in which the nerves themselves become damaged or
dysfunctional. May also result from altered central processing of
nociceptive input
• Many neuropathic pain syndromes
• Allodynia, hyperalgesia, atrophy of affected extremity, coldness in
affected area, dystrophic changes (hair loss, shiny appearance of skin)
• Often well-described sensation, location/radiation
• May be constant aching sensations with intermittent sharp, shooting,
burning, or electrical shock-like pain, jabbing, tearing, numb, dead,
cold
• Medications:
– Responds poorly to opioids
– Does respond to adjuvant analgesics, eg antidepressants,
anticonvulsants
Classification of pain based on disease:
Cancer-Pain
Associated with:
– Cancer disease process (infiltration of organs, compression
of structures by an expanding tumor, production of mediators, etc)
– Cancer treatment (eg chemotherapy-induced neuropathies,
radiation-induced skin burns, surgery-induced wounds)
• Prevalence ranges 60 to 80% in advanced cancer patients.
When present, cancer pain is moderate or severe and interferes with
activity and enjoyment of life
• “Cancer pain is a complex, temporally changing symptom which is the
end result of mixed mechanism pain. It involves inflammatory,
neuropathic, ischemic, and compression mechanisms at multiple sites.
It is a subjective, heterogeneous experience that is modified by
individual genetics, past history, mood, expectation, and culture.”
~Cleveland Clinic
• Clinical manifestations: mixture of acute (SNS) and chronic
(behavioral) changes at various times
• Treatment: multifaceted approach and use of potent medications
• Adequate pain control is a major factor affecting quality of life
Another type of pain: “Referred Pain”
• Perceived in an area other than the site of injury
– Examples include:
• pain of myocardial infarction being felt in the jaw or left arm
• shoulder pain after pelvic procedures
• diaphragmatic irritation from peritonitis
• Pain generally referred to other structures in the same sensory
dermatome
• Result of convergence of visceral nociceptor activity with primary
somatic afferents in the posterior horn of the cord
Common sites of referred pain, and origin of pain
Basic Approach to
Pain Management
Clinical Assessment of Pain
• Believe the patient’s self-report of pain
• Assess factors affecting pt’s pain report (medical,
medication history, psychological, spiritual, functional,
secondary gain)
• Take a careful history/ assess parameters of pain
– Onset and temporal pattern
– Location (site of pain/ widespread? Localized? Radiating?
– Duration of pain- constant? Come and go?
– Quality; “how would you describe your pain?“
– Intensity 0 to 10
“What number would you call your pain?”
– Modulating factors: does anything make it better? Worse?
– Previous treatment: what have you tried? Does anything work?
– Impact: how does this affect you? Your life, your activities?
World Health Organization: 3 Step Analgesic Ladder
Guide to choosing analgesic therapy
• Factors used in decisionStrategy:
making: Pt sensitivity,
allergy, prior opioid exposure TRIAL &
ASSESS
(naïve vs tolerant),
concurrent meds (drug intx,
CNS depressants)
• Current intensity of pain?
Mild, moderate, severe?
• Likely pain pathophysiology
somatic, visceral or
neuropathic?
• Route of administration?
PO, IV, SQ, IM, Rectal,
transdermal
PCA?
Guide to Monitoring Efficacy and Potential Adverse Effects
of analgesic drug therapy:
• Pre-drug therapy: Vital Signs and pain intensity;
(Respiratory rate is especially important pre-drug assessment when
administering opioid tx)
• OBSERVE functional status: activity restriction? Mood? Movement?
• Plan and administer a trial of the selected medication
• Re-assess post drug therapy at appropriate time interval for
reduction in pain intensity, presence of adverse effects
Reassess vital signs (RR)
Re-assess any key criteria observed prior to drug therapy
• DOCUMENT CRITICAL OUTCOMES:
– Degree of analgesia effected, RR and sedation level if opioid tx
– Any adverse effects
– ADLs
– Any aberrant issues or observations
• Adjust and manage therapy based on outcomes
Questions so far?
Non-opioid Analgesics:
Cyclo-oxygenase Inhibitors
Lehne, ch 71
&
Adjuvant Analgesics
Cyclo-oxygenase enzymes catalyze impt LOCAL rxs
(r/t synthesis of prostanoids and related compounds)
Functions served by the COX-1
enzyme- (“constitutive”- ie
produced in relatively constant
amounts in all cells of an
organism without regard to cell
environmental conditions)
In stomachProtect gastric mucosa
from self-digestion
In kidney Promote vasodilation;
maintain renal blood flow
In plateletspromote aggregatio
COX-?
In uterus-  Promote contraction
Functions served by the COX-2
enzyme- (“inducible” - ie formed
by a cell in response to the
presence of a particular substrate)
At sites of tissue injuryPromote inflammation
Sensitizes receptors to painful
stimuli
In the brainMediate fever;
Modulate perception of pain
In the kidneyssupports renal function
In blood vesselsPromote vasodilation
In colon- contribute to colon cancer
Effects of COX inhibitors:
ASPIRIN IRREVERSIBLY inhibits both COX-1 and COX-2
IBUPROFEN REVERSIBLY inhibits both COX-1 and COX-2
Acetaminophen exact mechanism not clear; appears to inhibit cox only
CENTRALLY  analgesic, antipyretic but not anti-inflammatory
Inhibiting COX-1 results largely in
harmful effects:
1- gastric erosion and ulceration
2- bleeding tendencies
3- renal impairment
BUT ONLY ASPIRIN protects
against MI and Stroke
Lehne, page 849
Inhibiting COX-2 results largely in
beneficial effects:
1- suppression of inflammation
2- alleviation of pain
3- reduction of fever
4- protection against colorectal
cancer
BUT two adverse effects
A- renal impairment
B- INCREASED risk of MI and Stroke
Agents aimed specifically at COX-2
inhibition not as safe as planned
of COX Inhibitors
Cyclo-oxygenase (COX) Inhibitors
• Initial drugs for mild – mod pain
• All have “ceiling effect” re analgesia
• All cox inhibitors act by preventing conversion of arachidonic
acid to prostaglandins/ prostanoids
• I. NSAIDS that inhibit COX-1 and COX-2
– NSAIDs vary in their relative inhibition of COX-1 or COX-2
– NSAID = Non-Steroidal Anti- Inflammatory Drugs
– First gen NSAID- salicylates: Aspirin
– First gen NSAID- (“nonsalicylates” or “nonaspirin” products)
- propionic acid derivatives: Ibuprofen and naproxen
- Over 20 other first gen NSAIDs: diclofenac, indomethacin, ketorolac
• II. NSAIDS that inhibit just COX-2
- Second gen NSAIDs (aka COX-2 Inhibitors): celecoxib
• III. Cyclo-oxygenase inhibitor with no antiinflammatory effect  is NOT an NSAID! Acetaminophen
 Appears to act only in brain (maybe spinal cord too)
NSAIDS- Often the first step in controlling pain
Therapeutic uses– Anti-inflammatory
– Analgesia/ relief of mild to moderate pain
– Antipyretic (fever reduction)
– Dysmenorrhea
– ASPIRIN ↓ risk of stroke and myocardial infarction (prevent platelet aggregation)
MOA- Inhibit cyclo-oxgenase (COX)
*Aspirin is IRREVERSIBLE inhibitor of cox.
 Effects decline as new cox is produced.
**All other NSAIDS are REVERSIBLE inhibitors of cox.
 Effects decline as drug is metabolized.
GENERAL RULE: Use at lowest effective doses for shortest time necessary
ADVERSE EFFECTS
– Significant risk of gastric ulceration, gastric bleeding, esp with drug intx!
Can lead to hospitalization or death
 consider prophylaxis (food, PPI, etc)
– Acute renal insufficiency/failure (caution elderly, renal compromise)
– Bleeding (caution when on other anti-coag)
Contraindications- several, see reference
− Pregnancy Category and LACTATION EFFECTS CHECK SPECIFIC DRUG
First Generation NSAID: Aspirin
• ASA (acetylsalicylic acid)
Excellent relief of mild-mod pain,
esp in MSK pain, Headache (not good for visceral pain)
Reduces fever; do not use in peds! (risk of Reye’s Syndrome)
Protects against thrombotic disorders
 Reduces risk of MI and ischemic Stroke
 Causes irreversible inhibition of platelet aggregation
 Effects last for the life of the platelet (8 days)  ↑ bleeding
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 Drug of choice for rheumatoid arthritis and some inflammatory
conditions; mechanism not thoroughly established
 Daily low-dose asa may be rec by PCP for CVA, TIA, MI, angina
 ?? Possible reduction in risk of certain cancers (colorectal)
Strengths: 75 mg, 81 mg, or 325 mg
Formulations: PO plain, buffered, enteric-coated, timed-release,
solution; PR
Dose depends on age of pt and condition being treated
Dosing for adult pain: 350-600 mg q4-6h
First Generation NSAID: Aspirin, cont’d
• Protein bound.
Hepatic metabolism: half-life depends on plasma concentration.
Renal excretion ↑ with alkaline urine. Does not damage liver.
• Significant potential for salicylate toxicity
– Tinnitus, sweating, headache, dizziness, resp changes
• And overdose poisoning- keep out of reach of children
• Adverse Effects– Gastric erosion and ulceration (give with food, other prophylaxis)
– Bleeding tendencies
– Renal impairment
• Contraindications: Do not use in pts with
– PUD (Peptic Ulcer Disease)
– Bleeding disorders
– Febrile children, esp if influenza or chickenpox, (Reye’s Syndrome)
– Hypersensitivity to aspirin or other NSAIDs
– Extreme caution: risk to pregnant woman & fetus; Preg Cat D
– Many other precautions
• Drug intx: anticoagulants; glucocorticoids; alcohol; other NSAIDS;
ACE-I; ARBs; Vaccines;
First Generation NSAID: (class of NONAspirin Products)
• Over 20 non-aspirin NSAIDs Examples: ibuprofen, naproxen, many others
• Different PK, PD. All reversibly inhibit cox-1 and cox-2 but they vary in relative
inhibition of cox-1 or cox-2.
• All have similar therapeutic indications, but vary in intensity; pts seem to
respond preferentially better to one or the other.
– Anti-inflammatory (rheumatoid and osteo-arthritis)
– Analgesic
– Antipyretic
– Some have special therapeutic applications, esp in neonates
• Similar adverse effects
– Gastric ulceration
– Bleeding
– Renal impairment
– Nonaspirin NSAIDS INCREASE risk of MI or Stroke
Use at lowest effective doses for shortest time necessary
– ONLY ASPIRIN REDUCES RISK of MI, ischemic CVA
– In people who take low-dose aspirin for protection against heart
attack and stroke, certain NSAIDs, (eg ibuprofen, naproxen), can
interfere with that protective effect.- APS
• People with hypersensitivity to aspirin are likely cross-hypersensitive to nonaspirin NSAIDs. Avoid. Concerns exist re: safety in pregnancy/ lactation
First Generation NSAID (nonaspirin product): Ibuprofen
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Ibuprofen Advil, Motrin, others
Prototype of the propionic acid derivatives
Generally well-tolerated, with low incidence of adverse effects
Inhibits cox-1 and cox-2
– Anti-inflammatory (arthritis)
– Analgesic (mild to mod pain)
– Antipyretic
– Superior in relief of primary dysmenorrhea (menstrual cramps)
Comparatively, ibuprofen has:
− Less inhibition of platelets than aspirin
– Less gastric bleeding than aspirin
– Higher risk of MI or CVA than aspirin
Multiple different oral doses and formulations
– Oral tablets, chewable tablets, oral suspension,
– Give with meals to minimize gastric distress
Two intravenous formulations (one for adults, one for neonates)
Doses for adults and children differ with age/body size and therapeutic
intent
Second Generation NSAIDs: COX-2 Inhibitors (coxibs)
• Drug development goal: create new drugs that suppress
inflammation and pain (but avoid GI ulceration and bleeding
caused by cox-1 inhibitors)
• COX-2 inhibitors: although suppress inflammation and relieve
pain, unfortunately several adverse effects:
– Clinically significant GI, bleeding risk still exists
– Risk of impaired renal function ( HTN, edema)
– And INCREASED risk of MI & Stroke!
•  All coxibs removed from market except celecoxib (Celebrex)
• Coxibs have a few highly specific indications
• severe juvenile rheumatoid arthritis, ankylosing spondylitis;
certain conditions with high risk of colon cancer (such as
hereditary/familial adenomatous polyposis)
– Last choice drug for most users
– Contraindicated: if known heart or PAD, avoid in sulfa allergy
• Extensive plasma protein binding ( intx with warfarin, etc!)
• Hepatic metabolism, renal excretion
Cyclo-oxygenase inhibitor with no anti-inflammatory effect:
Acetaminophen (APAP)
• #1 analgesic used in US
• MOA- not exactly clear; appears to inhibit cox CENTRALLY (but not
peripherally)
– Effective analgesic for mild – mod pain
(often combined with opioid to produce greater analgesia)
– Antipyretic
– NO anti-inflammatory or anti-rheumatic effects (not an NSAID)
– NO antiplatelet effects
– NO gastric ulceration
– Does not affect renal blood flow or cause impairment
• Adverse effects: risk of liver failure (esp if alcohol, cirrhosis)
rare at therapeutic doses, ↑risk with ↑doses
High acetaminophen doses in combo products being phased out
• ANTIDOTE: acetylcysteine (Mucomyst, Acetadote)
• Drug interactions: important to monitor (hepatic metabolism) –
especially alcohol! Other: Increased risk of bleeding with warfarin
highly under-recognized. Response to vaccines blunted by APAP.
Cyclo-oxygenase inhibitor with no anti-inflammatory effect:
Acetaminophen
To reduce risk of liver injury:
• Sum amounts of acetaminophen in ALL MEDICATIONS!
Teach pt to add up amounts of APA in all medications!
Do not exceed recommended daily doses
• In adults- 4000 mg/day
• If undernourished adults– 3000 mg/day
• In adult alcohol drinkers- 2000 mg/day
• Men: three or more drinks/day increases risk
• Women: two or more drinks/day increases risk
• If liver disease- consult MD
• Dft formulations, PO tabs, solution; PR, IV
• Dosing recommendations and max allowable
limits depend on age, body weight
• OFIRMEV = IV formulation
Combo Products:
aspirin, ibuprofen or acetaminophen + _______
• Caffeine
• Antihistamine
• Ibuprofen plus Proton Pump Inhibitor (Famotidine)
• Acetaminophen plus Ibuprofen
• ASA, ibuprofen or APAP plus opiods
Adjuvant Analgesics
• Definition: Adjuvant pain medications are drugs that are not
typically used to relieve pain, but theyhave independent
analgesic properties and are effective in some painful
conditions.
• APS - “Co-analgesics”
– Can be used alone, with non-opioids, or with opioids
– Especially effective against neuropathic pain
– Lehne text emphasizes that adjuvants are almost always
ADDED to opioid and non-opioid drug therapy,
by stating: Adjuvants are:
• Used to complement effects of opioids
• Used in combination with opioids
• Can enhance analgesia from opioids
• Manage symptoms that increase pain
• Treat SE caused by opioids
Adjuvants
Numerous drugs in diverse pharmacologic classes can act as adjuvants
in pain management:
• antidepressants, Tricyclic antidepressants (TCA); SNRI; duloxetine
• Antiseizure/ anticonvulsant meds, (esp the newer AEDs like
gabapentin)
• Skeletal muscle relaxants (eg cyclobenzaprine);
• antispasmodics (baclofen)
• sedatives
• anti-anxiety medications/ anxiolytics
• botulinum toxin
• Local anesthetics / antidysrhythmcs
• CNS stimulants- caffeine,
• Antihistamines
• Glucocorticoids (“corticosteroids”)
• neuroleptics
?? bisphosphonates
FYI:
LOCATIONS
where
adjuvants
work: for
interest sakewill not be on
quiz
Opioid Analgesics,
Opioid Antagonists,
and Non-opioid Centrally Acting
Analgesics (Adjuvant Analgesics)
Burchum and Rosenthal, Chapter 28
A few terms
• Opiate – a specific term that refers only to compounds present in
opium, obtained from the poppy plant (eg codeine, morphine)
• Opioid- a general term that refers to any drug (natural or synthetic)
that has actions similar to morphine
• Opioid naïve- patient who has never taken opioids before; physiology
has not been exposed to opioids
• Opioid-tolerant= a state in which a person requires higher doses of
medication in order to obtain the same response as induced by the
medication when therapy began
• Tolerance is a normal and expected response that develops to a
variety of different classes of medications
• Specifically in response to opioids, tolerance develops after 2 – 3
weeks. Tolerance develops to some, but not all, effects of opioids.
• Tolerance develops as a consequence of physiological adaptation
of the receptors to the drug.
• Pain threshold- the minimum intensity of a stimulus that is perceived
to be painful
Opioids, opioid receptors, and effects of activation
• Opioid analgesics are the most effective pain relievers available
• Endogenous opioid peptides are produced naturally in the human
body where they serve as neurotransmitters, neurohormones and
neuromodulators. Precise roles not understood.
• Enkephalins• Endorphins• DynorphinsOpioid receptors- three main classes; proportion genetically determined
• Endogenous opioid peptides act on mu, kappa, and delta
• Pharmaceuticals primarily activate mu, weakly activate kappa
• Mu receptors: analgesia, respiratory depression, euphoria,
sedation, physical dependence
• Kappa receptors:
−analgesia, sedation; dysphoria, delirium
• Delta receptors: important to endogenous opioid but not so much
opioid pharmaceuticals
Classifications of drugs that act at opioid receptors
 Pure opioid agonists activate mu & kappa
Analgesia, euphoria, sedation, respiratory depression,
physical dependence, constipation, and other effects
− Two subgroups:
Strong opioid agonists (prototype morphine)
Moderate - strong opioid agonists (prototype codeine)
 Agonist-antagonist opioid (aka “partial agonists”)
– Produce low to moderate receptor activation when
administered alone, but will block the actions of a full agonist
if the two are co-administered (prototype pentazocine)
 Pure opioid antagonist- block mu and kappa
– Used to reverse resp and CNS depression caused by
overdose of opioid agonists (prototype naloxone)
opiates
Strong opioid analgesic: morphine
• Morphine = prototype
Morphine is the standard to which other opioids are compared
• Primary use: relief of moderate to severe pain
• MOA: appears to mimic endogenous opioids,
acting primarily at mu receptors
• When mediating pain, endogenous opioids and
morphine-like drugs bind to receptors in brain
and spinal cord
• Source: originally extracted
from the dried juice
of the poppy seedpod
Morphine- indications, therapeutic effects, adverse effects
• Uses
– Acute trauma or post-operative pain
– Labor and delivery (but can suppress uterine contrx and cause
neonatal resp depression )
– Chronic pain (eg cancer or other conditions)
– Pre-op sedation and anxiety
– Chest pain and dyspnea from myocardial infarction
– Dyspnea from LV failure, pulmonary edema, dying pts
– Many applications for relief of moderate to severe pain
• Therapeutic effects and side effects: treatment goal?
analgesia, relief of dyspnea, cough suppression
sense of well-being, ↓anxiety,
sedation/drowsiness, respiratory depression,
suppression of bowel motility, urinary retention,
orthostatic hypotension, emesis, miosis, biliary colic, pruritis
• Managing adverse effects- discussed later
• THERE IS NO CEILING EFFECT TO ANALGESIA from opioids
• LIMITATION IS ESTABLISHED BY THE SIDE EFFECTS
Morphine Pharmacokinetics
• Routes of administration and formulations
– many options, see Table 28-5 (Lehne, p268)
– Rate of onset, peak, and duration- see Table 28-5 (Lehne, p268)
• Dosing- highly individualized! “opioid-naïve” vs opioid-tolerant
– Very strongly recommend starting at very low doses!
– Sharp, stabbing pain – higher doses
– Infants & elderly – careful dosing
– Decrease dosage as pain decreases
(eg immediate post-op compared to a few days after surgery)
• Never administer an IV dose rapidly – emesis and other
• Lipid solubility is poor. For analgesia, must cross BBB. Only a small
amount of the drug actually gets to site where analgesia is induced
• Hepatic elimination
– VERY SIGNIFICANT first pass elimination (if given orally)
– Doses between PO and IV differ significantly! (IV much lower)
– Liver disease- effects longer and more intense (possibly)
– MANY drug interactions related to CYP450
• Renal excretion
Routes- many options, depends on drug
• Oral – immediate & sustained release
• IM injection
• IV injection
– IV Push
– Patient controlled analgesia (PCA)
• Demand dosing (button) and/or basal continuous infusion
• Epidural
– Patient controlled analgesia (PCA)
– More likely to have basal (continuous), may also see demand
dosing
• Transdermal
– Patch, lollipop
NEW SLIDE ADDED AFTER LECTURE
• When morphine is administered orally, it undergoes
very significant metabolism by the liver (ie the “first
pass effect”)
– Among patients who take morphine regularly,
Morphine ONE mg IV ~ Morphine 3 mg BY MOUTH
• Oral oxycodone is actually more potent medication
than oral morphine!
• Oxycodone 20 mg BY MOUTH actually has
a relatively equal analgesic effect as
Morphine 30 mg BY MOUTH
Some opioids have biologically significant metabolites
 Meperidine –
– With repeated use, a toxic metabolite can accumulate and
can cause seizures
– Should not be used on an ongoing or routine basis
– Many drug intx
 Methadone –
− Strong pain relief
− Also used to treat opioid addiction: for 3 reasons
− prevents abstinence symptoms
− controls physical cravings (but not emotional)
− binds to opiate receptors tighter than drugs like heroin or
morphine, therefore little or no incentive to abuse
− metabolite has long half-life!
− Delayed suppression of respiration- risk of death
− Prolongs the QT interval – risk of dysrhythmias and death
 Codeine – metabolite augments emetic effects
MANAGING OPIOID
ADVERSE EFFECTS
Respiratory Depression and Arrest
• Occurs to both opioid-naïve and opioid-tolerant individuals
– although people can develop tolerance to resp depr effect
 Primarily through activation of mu receptors
• Before administering opioids, assess vital signs:
– Withhold opioid and notify provider for ↓LOC or
respiratory rate less than 12 breaths/ minute (adult)
• Careful follow-up monitoring required
– esp the very young, very old, and anyone w/ resp disease
• Timely and appropriate assessment of
– level of consciousness, respiratory rate and oxygen saturation
• At equianalgesic doses, all pure opioid analgesics depress respiration
to same extent
• Resp depr potentiated by concurrent use of CNS depressants
– Eg alcohol, barbiturates, benzodiazepines
• Treatment: naloxone (Narcan)
(Naltrexone is a synthetic opioid antagonist used chiefly in the
treatment of heroin addiction.)
Constipation- BOWEL REGIMEN ESSENTIAL
• Due to
–  in propulsive intestinal contractions
–  non-propulsive contractions
–  tone of anal sphincter
–  secretion of fluids into intestinal lumen
• Can develop within a few days of starting therapy
–  risk with pharmacological and nonpharmacological
measures. Bowel regimen essential
– “Here’s your opioid. Here’s your stool softener.”
• Newly developed opioid antagonist, not widely used yet.
Valuable because tolerance to constipation does not
develop! Methylnaltrexone specifically blocks the opioid
Urinary retention
• Opioids cause urinary hesitancy and urinary retention
–  tone in the sphincter of the bladder
–  tone in the detrusor muscle
• Can  pressure within the bladder
•
•
•
•
Opioid can also cause  awareness of bladder stimuli
Encourage to void every 4 hours
Monitor input & output (I & O)
Bladder scanner, catheter
Orthostatic Hypotension
•  BP by
– Blunting baroreceptor reflex
– Dilating peripheral arterioles and veins
• Due to morphine–induced release of histamine
• Increased risk if dehydrated, certain other meds, at risk
for falls
• Teach pts re: how to deal with orthostatic hypotension
Biliary colic
• Increased muscle tone
• Why opioids may be initially withheld in a patient
presenting with abdominal pain of unknown origin
• Fentanyl causes less spasming at the sphincter of Oddi
than other opioids.
Additional Side Effects
Cough suppression
– Act at opioid receptors in medulla to reduce cough
– Codeine-based cough remedies
– Encourage cough and deep breathing for less mobile, or
otherwise at-risk patients
Emesis
− opioids promote n/v
− chemoreceptor trigger zone of the medulla
− vestibular component
Other: Elevated ICP, Sedation, Euphoria, Dysphoria, Miosis,
pruritis, adverse effects from prolonged use, Birth defects
and neurotoxicity
Precautions
•
•
•
•
•
Decreased respiratory reserve
Pregnancy (category C)
Labor / Delivery
Head injury
Other: related to side effects & metabolism
(persons with hypotension, ileus, alcoholism, etc)
Opioid Overdose: serious risk of brain injury/ death
• Classic triad
– Coma
– Respiratory depression
– Pinpoint pupils (miosis)
• Dire concern to abusers
• Rationale for police, firefighters, partners, parents and others to be
trained in how to administer naloxone, and to be supplied/have
immediate access to naloxone at all times
• Treatment of overdose
– Immediate ventilatory support
– Opioid antagonist
• Naloxone (Narcan) (IV, Subcut, IM, intranasal spray)
−withdrawal symptoms may appear within minutes
−severity and duration of withdrawal syndrome is related to the
dose of naloxone and to the degree and type of opioid dependence
• Opioid diversion/ abuse/
misuse is a major national
public health problem
• “Death by Fentanyl” is a
documentary that aired on
National Public Radio on
Feb 4, 2016
• Worth viewing
• 12 minutes
• https://hereandnow.wbur.org/2016/02
/04/death-by-fentanyl
Other strong opioid agonists
• Created for strong analgesia and may have
qualities making them good alternative
• Fentanyl, hydromorphone (dilaudid) –
similar to morphine
• Methadone and meperidine –
some important differences from morphine
None of the drugs are superior to Morphine
**?
Other strong opioid agonistsFentanyl & Hydromorphone
Fentanyl
• High potency
~100x that of Morphine
• Short peak & duration:
onset 15 min, lasts 1-2h
• Routes:
parenteral (IVP, PCA),
transdermal (Duragesic)
transmucosal (Actiq)
Hydromorphone
(Dilaudid)
• Dosed PO or IV
• Smaller dose than
morphine- start at 0.1mg
• Similar onset & duration
as morphine.
• Often used in morphine
intolerant patients
Patient Controlled Analgesia (PCA)
Excellent for management of acute pain, if pt is capable of using:
1- pt self-administers bolus (lockout interval; 1 dose/ x minutes)
2- Device also has a lock-out for maximal medication administered in a
larger time interval such as a one hour period or a 4 hour period.
3- Evaluate analgesic requirements. Set basal rate (prn)
Fentanyl Transdermal Patches
• Read package insert.
• Become familiar with product used at your institution. Speak with unitpharmacist re: questions or concerns.
• Caution re: rate of onset may not be until 6-12 hours. BTP med required.
• Caution: rate of “offset”. If a dermal reservoir is developed, then drug
effect will persist for “awhile” even after patch is removed.
• Disposal in tamper-proof manner.
• Only for use in pts whose analgesic needs are known! Use equianalgesia
table, apply a lower dose and have BTP med available as prn
• BTP = break through pain
Equianalgesia
Other strong opioid agonists- Methadone
● Preferred in some settings due to:
 long half-life
 low cost
• Use in analgesia & in drug-treatment/ behavioral health
programs
• Acts at NMDA receptors – good for neuropathic pain
• Very hard to titrate (equianalgesic tables don’t work)
• Accumulation causes LATE side effects - CAUTION!!!
Moderate to Strong Opioid Agonists: Codeine
•
•
•
•
Discovered in 1830s
Weak analgesic (about ½ as potent as morphine)
Combined with APAP or ASA
Effective cough suppressant
• Recent warning – in some women higher levels accumulate
in breast milk than mother’s plasma (rare but serious)
Moderate to Strong Opioid Agonists: Oxycodone
• Useful analgesic, only given orally
• Often combined with ASA (Percodan) or APAP (Percocet)
• May see controlled release (Oxycontin) scheduled with a PRN
immediate release (Oxycodone) for breakthrough pain (BTP)
• Risk of abuse – r/t public attention
– Increased risk of abuse – crush & snort or inject
(recently reformulated)
Other Moderate to Strong Opioid Agonists
• Hydrocodone (w/ APAP = Vicodin)
– Schedule II since 2014
• Propoxyphene (w/ APAP =Darvon)
– pulled from market in 2010
– Caused ECG changes
Combination Drugs - caution
• Many combined with APAP (acetaminophen)
– Hydrocodone, codeine, oxycodone
• Be careful not to exceed maximum 24-hour APAP
– 4 grams in most adults
– 3 grams in elderly and high-risk
– New FDA rules (2014) say combo products need to
contain lower doses of APAP (less than 325mg/dose)
• Hepatic failure may result from attempted overdose due to
APAP, not opioid.
Partial Agonists
•
•
•
•
Antagonists at mu receptors & agonists at kappa
Reduced abuse & resp. depression
Less powerful analgesia
If given to pt who is on a pure opioid – may precipitate
withdrawal syndrome
Examples:
 Buprenorphine/Naloxone
 Pentazocine (Talwin)
 Butrophanol (Stadol)
Opioid antagonists: Naloxone
• Blocks the effect of opioid agonists
– act as competitive antagonists at opioid receptors
• Naloxone (Narcan) is most common
– Absence of opioid: no pain relieving, euphoria, etc effects
– Watch half – life carefully:
• Will probably need to re-administer if respiratory
depression recurs
– If patient requires ongoing pain relief, administer naloxone
in carefully titrated doses!
– Patient is at risk of going into a severe pain crisis
(and/or withdrawal) if all opioid effect is blocked
– If patient is at risk of opioid overdose- and you’re not sure
if overdosed or not – best to give antagonist
Nursing Implications
• Reassessment of pain
– Depends on peak and half-life
– Know the common drugs used in your care setting
• Reassessment of side effects
– Safety = resp rate
– Depressed respiration may be predicted by sedation!
– Monitor for constipation
• Patient education
– Many are needlessly afraid of addiction.
– Teach patients why, physiologically, it is important to
control pain.
Which Route is Best?
Tolerance
Tolerance
– Expected, normal response
– Occurs as a consequence of physiological changes
in opioid receptors which take place after 2-3 weeks
of therapy/use of opioids
– Pt requires higher doses to obtain same response
 Develops with analgesia, euphoria, sedation,
respiratory depression
Does not develop with constipation, miosis
– Incomplete cross-tolerance to other opioid agonists
(opioid rotation)
Physical Dependence
• “Dependence is a universal physiologic/
pharmacologic phenomenon following regular use
of opioids formore than 14 – 20 days.” APS
• State in which abstinence syndrome occurs if drug
abruptly stopped
• Intensity and duration of abstinence syndrome is
dependent on
– Half-life of drug
– Degree of physical dependence
• Intensity of withdrawal parallels the degree
of dependence
WEANING
• APS, p 34
Abstinence syndrome
• Symptoms
– Initial:
• Yawning, rhinorrhea, sweating
– Develops into
• Anorexia, irritability, tremor, anxiety, chills alternating with hot
flashes, salivation, lacrimation, goosebumps (piloerection)
– Finally
• n/v, diarrhea, abd cramps, muscle spasm, bone & muscle pain,
weakness, kicking movements
• Time course depends on half-life:
– Short half-life eg Morphine, hydromorphone- sx may appear in 6 – 12
hours and peak at 24-72 hours
– Long half-life eg methadone- sx onset not for several days and be less
florid
• Giving opioid will reverse effects
-cross dependence.
• Neonates?
Abuse
Opioid analgesics subject to abuse because of
pleasurable sensations
- and ease of obtaining!
Controlled Substances Act
Schedule I – V
– Schedule II – strong opioid agonists
– Schedule IV – agonist antagonists (lower abuse
potential)
Definitions in Controlled Substance Schedule
• Schedule I
– NO currently accepted medical use in the United States.
Examples: heroin, (LSD), marijuana
• Schedule II
– High potential for abuse.
Examples: hydromorphone (Dilaudid), methadone, oxycodone,
and morphine
• Schedule III
– Potential for abuse less than substances in Schedule I/II.
Examples: Tylenol with Codeine
• Schedule IV/V Controlled Substances
– A lower relative potential for abuse.
Addiction
*not the same as physical dependence
Definition:
Behavior pattern characterized by continued
used of a substance despite physical,
psychological, or social harm.
Physical dependence not required for addiction to
occur but it can contribute to addictive behavior
Minimize fears of addiction
Opiophobia
• Rare when used for acute pain
• Some individuals prone to abuse & others who are not
• Suffering is unacceptable
Use lowest effective dose for the shortest time
needed!!
What if . . .
You have a pt who doesn’t look in pain who is
requesting pain medication.
You have a pt who you suspect is abusing drugs who is
requesting pain medication.
You have a pt who looks to be in pain but is denying
discomfort and refuses to take pain medications.
Sound alike: HEADS - UP
TRAMADOL (ULTRAM)
VS.
KETOROLAC (TORADOL)
Tramadol (Ultram)
Atypical opioid
Actions:
• Mu agonist
• Blocks serotonin and norepinephrine uptake
Low abuse potential (not scheduled)
Risk of suicidal ideation, seizures
Dosing: oral, 50-100 mg, peak at 2h
Pain Management
in Patients with Cancer
(and special populations)
World Health Organization: 3 Step Analgesic Ladder
Guide to choosing analgesic therapy
• Step 1—Mild to moderate pain
– Nonopioid analgesic
– NSAIDS and acetaminophen
• Step 2—More severe pain
– Add opioid analgesic,
oxycodone, hydrocodone
• Step 3—Severe pain
– Substitute opioid—morphine,
fentanyl
Pain management in special populationsthe young, the elderly, and disabled/non-verbal
Inadequate pain treatment can result in persistent behavioral
changes and physical changes in the CNS
 Young babies/children
– Neonates/infants often receive inadequate pain management
→ BBB, development of liver, kidney
→ Infants have pain perception
– Assessment challenges
 Elderly
− Pain perception does not decrease with aging, but communication
and expression of pain may vary
− Heightened drug sensitivity,  risk of SE & ADR
 Disabled/ nonverbal- anticipate needs; do not withhold
meds; monitor carefully
Remember!!
 One of the most important responsibilities you will ever have as a
nurse is to help manage pain effectively for patients.
 Skill and expertise in pharmacologic and non-pharmacologic
measures to safely relieve pain is a highly sought-after nursing
expertise
 Take it seriously, keep up with the literature, and remember that
the mistreatment of pain continues to be a major problem in
health care.
 Additional training available from
Puget Sound Pain Consortium
http://www.coperems.org/cope-rems-training/
and UW CNE programs
Resources and References
• American Pain Society
• World Health Organization
• Offers guidelines specifically for low-resource settings
• International Association for the Study of Pain
• Puget Sound Pain Consortium
http://www.coperems.org/cope-rems-training/
• Univ of Washington Continuing Nursing Education hosts and
annual conference (~January each year)
• Burchum, J.R., & Rosenthal, L.D. (2016). Chapters 28, 29, 71. In
Lehne’s Pharmacology for Nursing Care, 9th edition. St. Louis,
Missouri: Elsevier Saunders.
•