Transcript The Client in Pain: Pathopharmacologic Principles

The Patient in Pain:
Pathopharmacologic Principles
Wanda Lovitz, APRN
Pathopharmacology of Pain:
Objectives

Explain role of nociceptors in pain.

Differentiate between A-delta & C-fiber neurons.

Discuss the neurotransmission modulation of pain receptors in the
spinal cord and brain.

Discuss the endogenous analgesic mechanisms.

Compare and contrast the three classifications of analgesics.

Describe the Classification, MOA, Indications, Adverse Reactions,
and significant nursing implications for selected opioid and nonopioid, and adjuvant analgesics.
Pain is both a
protective and an
unpleasant physical and
emotionally disturbing
sensation
originating in PAIN
RECEPTORS
that respond to a
number of
stimuli that threaten
tissue integrity
Nociceptors
• “Pain receptors”
• None/very few in:
– Specialized receptors
– Brain
– Peripheral pain fibers
– Alveoli
with Free Nerve Endings
• Widely distributed in:
– Skin, dental pulp, periosteum,
meninges
– Some internal organs
– Deep tissues
Nociceptive stimuli
• Nociceptive stimuli – stimuli of such
intensity, that they cause, or are close to
causing, tissue injury
– receptors respond to sharp objects, electric
current, application of heat and cold to the skin
– receptors also respond to chemical stimuli
•
chemical mediators
• Low intensity…..nociceptors are not
activated
Inflammation and Pain
• Signs & Symptoms of inflammation produced by
chemical mediators
– PAIN, swelling, redness, heat, immobility
• Chemical mediators are present in the plasma and
activated by tissue injury
– Histamine
– Achidonic acid metabolites- leads to the production of
inflammatory mediators
• PROSTAGLANDINS AND LEUKOTRIENES
WHAT ARE PROSTAGLANDINS?
•
•
•
•
Chemicals that promote
INFLAMMATION, PAIN AND FEVER
They also protect the lining of
STOMACH from effects of acid
Promote BLOOD CLOTTING by
activating platelets
Also affect KIDNEY function- dilate
blood vessels leading to the kidneys
• Enzymes that produce
prostaglandins –cycloxygenases
(COX)
•
2 TYPES OF COX ENZYMES
–
•
Both produce prostaglandins that
promote inflammation, pain, and fever
But ONLY COX-1 activates platelets and
protects the stomach
–
COX-1  Block this and can have clotting
problems and GI problems
–
COX-2 Block this and reduce pain,
fever, and inflammation
PAIN
Stimulus is OUTSIDE
the CNS
Stimulus is WITHIN the CNS
Nociceptive
(Pain receptors)
Activated in response to
actual or impending
tissue injury
Neuropathic
Arises from DIRECT
injury to nerves
Consequence is
NOCICEPTIVE pain
Referred to as
NEUROPATHIC
pain
Trauma to CNS or PNS
NOCICEPTIVE Pain
Somatic Pain
Involves MS system
•Complaints
• Constant
• Achy
•Location
• Well-localized in skin and
subcutaneous tissues
• Less well-localized in bone
• Muscle
• Blood vessels
• Connective tissues
•Examples
•
•
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•
•
•
•
•
Incision pain
Bone fractures
Bony metastases
Degenerative joint/spinal
disease
Osteoarthritis
Rheumatoid arthritis
Peripheral vascular disease
Chronic stasis ulcersc
Visceral Pain:
Involves organs
•Complaints
•
•
•
•
Cramping
Splitting
N/V
Diaphoresis
•Location
• Originates in
internal organs or linings
• Poorly localized
• Diffuse
• Deep
•Examples
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•
•
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•
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Kidney stones
Appendicitis
Bladder spasms
Constipation
Organ metastases
Spastic bowel
Inflammatory bowel dx
Heart attack
Chronic hepatitis
NEUROPATHIC Pain
Neuropathic pain:
Involves nerves
•Complaints
•
•
•
•
•
•
Shooting
Burning
Electric-shock
Sharp
Numb
Motor weakness
•Location
• Originates in injury to
peripheral nerve
• Spinal cord
• Brain
• Poorly localized
•Examples
• Diabetic neuropathy
• Postherpetic neuralgia
• Tumor related nerve
compression
• Phantom limb pain
• Trigeminal neuralgia
• Central post-stroke pain
Physiology of Pain: Nociception
Stages of nociception
1. TRANSDUCTION
•
•
Painful stimuli converted to action
potentials at the sensory receptor
Substances/chemical mediators
released as a result of direct injury and
inflammation
– Prostaglandin an important
mediator –lowers the pain
threshold
– Many other neurotransmitters
and neuropeptides involved in
pain transmission
2. TRANSMISSION
•
Action potentials move from peripheral
receptors to the spinal cord and then
the brain
– A delta and C fibers are the
primary sensory fibers
Stages of nociception
3. PERCEPTION
•
Brain receives the pain signals and interprets them
as painful
–
–
–
Influenced by attention, distraction, anxiety, fear,
fatigue, previous experience and expectation
Pain threshold
Pain tolerance
4. MODULATION
•
Synaptic transmission of pain
signals is altered
–
–
–
Presynatic inhibition
Opioids such as endorphins mediate
presynatic inhibition
Morphine mimics the effect of endorphins
The body does make attempts to rid of
its own pain…
Its main defense mechanism:
ENDORPHINS (endogenous)
Located in brain & close to pain receptors in nerve
fibers, ascending/descending pathways
In fact, morphine is referred to as the
“exogenous endorphin”
Dorsal horn – connects
peripheral and CNS
•
The chemical mediators  translate the
noxious stimulus into ACTION
POTENTIALS that are transmitted to the
DORSAL HORN of the spinal cord
The dorsal horn of the spinal
considered the “GATEWAY”
between two sensory nervous systems
•
Pathway of Pain…..Block the
pain…..Relieve the pain
• Gate Control Theory
– If we can BLOCK the
pain before it gets to
the brain, we can
STOP the pain
Dorsal Horn of Spinal
Cord
GATE CONTROL THEORY: This gate can OPEN and CLOSE
To better understand Gate Control Theory…
let’s first look at types of nerve fibers
There are 4 TYPES OF NERVE FIBERS
that carry impulses to the brain:
Nerve Fibers
A – delta
Small diameter
Myelinated – Rapid transmission of pain
Pain is sharp, stinging,cutting, and
pinching. Is localized
C fibers
Small diameter
Unmyelinated –Slow transmission of
pain
Pain is dull, burning, aching. Poorly
localized
A- alpha
Large diameter
Do NOT transmit pain signals
A- beta
Large diameter
Do NOT transmit pain signals
Gate Control Theory
• Built around the premise that:
– LARGE DIAMETER nerve fiber stimulation
•
(A alpha & A beta)
–
causes the gates to CLOSE
» aka – touch, rubbing skin, massage, distraction, acupuncture, etc
– SMALL DIAMETER nerve fiber stimulation
• (A delta & C fibers)
• causes the gates to OPEN
• aka nociceptor stimulation
– Two pathways of pain transmission:
» FAST PAIN – A delta myelinated fibers
» SLOW PAIN…C fibers unmyelinated fibers
Gate Control Theory: Explanation
• Activation of nerves that DO NOT transmit
pain signals
– A alpha – Large diameter nerve fibers
– A beta – Large diameter nerve fibers
– Can INTERFERE with signals from pain fibers
• A delta – Small diameter nerve fibers
• C fibers – Small diameter nerve fibers
• Thus INHIBITING an
individual’s perception of pain
• Theory works best with ACUTE pain
Pathophysiology of Pain Control
The Gate is OPEN an and pain is perceived
CLOSING the Gate with acupuncture –
diminishing the pain
What NON-PHARMACOLOGIC
measures can nurses take to
decrease pain?
• Adjuvant therapy:
– Massage (hand massage), therapeutic touch,
application of heat and cold, music
therapy,TENS units, distraction
• ALL stimulate the large diameter A alpha and A
beta
• Remember that stimulation of these
fibers “CLOSES THE GATE”
IMPORTANT CONCEPT for anyone
managing the patient’s pain…
If one can inhibit the nerve
impulse BEFORE it
reaches the thalamus/cortex,
one can decrease the
PERCEPTION OF PAIN.
Managing the Patient’s Pain
Pharmacologically… Blocking
PAIN from the BRAIN
OPIOID
NON-OPIOID
ADJUVANT
Morphine Sulfate
non-NSAID
acetaminophen/Tylenol
gabapentin/Neurontin
pregablin/Lyrica
Commonly rx for
neuropathic pain
Classified as:
anticonvulsant
although rarely used for
seizure control
Morphine antagonist/antidote
naloxone/Narcan
NSAID (non-selective COX inhibitor)
acetyl salicylic acid/ASA/BayerAspirin
hydromorphone/Dilaudid
meperidine/Demerol
NSAID (non-selective COX inhibitor)
Ibuprofen/Advil & Motrin
codeine sulfate
NSAID (non-selective COX inhibitor)
naproxen/Naprosyn & Aleve
oxycodone + acetaminophen/Percocet
NSAID (selective COX-2 inhibitor)
celecoxib/Celebrex
hydrocodone +
acetaminophen/Lortab,Vicoden,Norco
NSAID (non-selective COX inhibitor)
ketorolac/Toradol
oxycodone +
ASA /Percodan
tramadol/Ultram (atypical opioid)
Antidote for acetaminophen
acetylcysteine/Mucomyst
3 Classifications of Analgesics
(analgesics relieve pain without causing loss of consciousness)
OPIOID analgesics any drug that has actions similar to morphine
 Agonists
 Morphine Sulfate
 Antagonists
naloxone/ Narcan
NONOPIOID analgesics
 Tylenol
 NSAIDS (including ASA)
 ADJUVANT THERAPY
 Other drug classifications that help relieve (usually neuropathic) pain
 gabapentin (Neurontin)
 pregabalin (Lyrica)
3 Classes of Opioid Receptors
1. Mu
 MOST IMPORTANT pharmacologically
Opioid analagesics act primarily by activating mu receptors
 Activation results in analgesia, RESPIRATORY
DEPRESSION, euphoria, decreased GI motility, miosis &
sedation
Can cause physical dependence
2.
Kappa  weak activation by opioids
3.
Delta  no activation by opioids
Classification of Opoids
1. Opioid Agonist
◦
Analgesia, resp depression, etc
2. Opioid Antagonist
◦
Reversal of resp depression & CNS depression
◦
Used as ANTIDOTE to reverse action of
opioids
Opioid Agonists
MOA:
Combine with opiate receptors to produce
an analgesic effect by altering one’s
PERCEPTION of pain
Blocks nociceptive transmission
Indications for use:
Moderate to severe pain
Pain Scale of greater than 3
Mild 1-3
Mod 4-6
Severe 7-10
What is the ceiling
effect?
Definition: Ceiling Effect
↑ dosing results does not result in 
pain relief, only  side effects
 Example: Analgesic ceiling effect of Tylenol is
4Gm/24H. Giving more than 4Gm will not provide
increased analgesia, but could increase SE
 ‘Tis a good thing → there is NO CEILING
 EFFECT for PURE OPOIDS (Morphine, Fentanyl)
We can continue to increase the dose until
pain is relieved!!
Opioid Agonists: Adverse Effects
o PUPIL CONSTRICTION – sign of toxicity/overdose
o RESPIRATORY DEPRESSION
opioid-naïve pts)
(esp.
o CONSTIPATION, CONSTIPATION,
CONSTIPATION!
o May lead to a paralytic ileus
o CNS depression - COMA
o N/V
o Physical tolerance & (physical & psychological)
dependence
o Hypotension
o Urinary retention
o Pruritis
What is a paralytic ileus?
Is considered a “pseuo-obstruction”
There is a partial or complete blockage of the bowel
May be caused by opioids d/t decreased peristalsis
The bowel sounds are very diminished or absent
There is abdominal distension and pain
Opioid Agonists: Interactions
– Additive RESPIRATORY DEPRESSANT
effects with other CNS depressants:
• ETOH
• Antihistamines
(Benadryl, Claritin, Zyrtec)
• Barbiturates (Seconal, Phenobarbital)
• Benzodiazepines
(Xanax, Valium)
• Phenothiazines (anti-psychotics –Thorazine, Haldol)
Opioid Agonists: Morphine
• *morphine sulfate
(Duramorph, MS
– GOLD STANDARD
Contin, Roxanol)
DRUG OF CHOICE for
SEVERE
pain
– Pure opoid agonist
– Drug effect: analgesia, sedation, euphoria, respiratory
depression, cough suppression, and suppression of bowel motility
–
Prototype; schedule
II –
–
Derived from opium (poppy plant)
moderate to high potential for abuse
– Indications: Acute or chronic severe pain
•
•
•
Without causing loss of consciousness
PO  chronic pain; high doses 2° first-pass effect
IV, extended/immediate release, epidural
– Give very slowly IV; over 4-5 minutes
(7-10/0-10)
MOA: Morphine ---- a mu agonist
mimics the action of endogenous opioids at the mu receptors
→ morphine binds to the mu receptor and creates a response
Opiod Agonist:
hydromorphone/Dilaudid
• Opoid similar to morphine
– Semi-synthetic
• Schedule II
• Indication: SEVERE pain
Opioid Agonists: Demerol
•
meperidine hydrochloride
(Demerol)*
– Synthetic opioid
–
Schedule II
– Indications: Moderate to Severe Pain
• Weaker than morphine & shorter duration of action
•
•
•
•
Less respiratory depression
PO is half as effective as IV
Lots of drug/drug interactions
Short T1/2
– With REPEATED doses, Demerol breaks down to toxic metabolite
normeperidine 
•
DOSE DEPENDENT ADVERSE REACTION: CNS stimulation/seizures!
– AHCPR (1992) – avoid in pain management when multiple doses
will be given
• So….only used when one or two doses will be given
Opioid Agonists: Oxycodone
• *Oxycodone
– Schedule II
– THE #1 drug used across the street on med-surg floors
•
SEMI-SYNTHETIC DERIVATIVE OF CODEINE
– po only
– Indications: Moderate to severe pain
– More potent (10X) than codeine!!
– Drug of abuse!
• Oxycodone & acetaminophen (*Percocet)
•
Oxycodone & ASA (Percodan)
• Time-released (Oxycontin)
– High abuse potential. Reformulated in 2010 making the tablets
harder to crush and “snort”
Opioid Agonists: fentanyl/Duragesic
– *fentanyl /Duragesic
– schedule II
– Indications:
–
Synthetic opioid for moderate- severe pain/surgical induction/ and
CHRONIC PAIN
•
Less potential for resp depression and abuse
– Adverse Reactions:
• Pure opoid agonist: similar actions to Morphine
–0.1 mg = 10 mg morphine so 100X as potent as Morphine
– Transdermal
duration
patches (“Duragesic Patch”) – (onset = 6 hrs) 72 hour
• Also IV, IM
• Fentanyl Oralet – a lozenge (with handle) available for
anesthetic pre-medication for kids/adults
Opioid Agonists: Codeine
•
*codeine sulfate
–
Schedule II – codeine alone
Schedule III – codeine combined with another analgesic
–
DERIVED FROM OPIUM
–
• Drug Effect: Analgesic,sedation,euphoria
Effect is dose dependent
–
Analgesic (30 mg)
–
Anti-tussive (10 mg)
– Indications:
•
•
–
–
Often given WITH ASA or acetaminophen for added analgesia
opioid + nonopioid = synergistic effect
•
–
–
mild to moderate pain
like morphine, but WEAKER
Ex.: “Tylenol #3”
PO – has ceiling effects
Side Effects are dose limiting
Why is codeine very effective for some and
not effective for others?
• Codeine is a PRODRUG
– inactive when administered and must be converted to an active form
to be effective
• Liver converts about 10% of each dose of codeine to morphine via
the CYP2D6 enzyme
• People who lack the effective gene for CYP2D6 cannot convert
codeine to morphine
– So codeine is NOT effective
• People who are ultrarapid metabolizers (carry multiple copies of
CYP2D6 gene) rapidly convert codeine to morphine
– Codeine is unusually effective
Opoid Agonist: Hydrocodone
Schedule III → changing to Schedule II
•
Most widely prescribed drug in US
 Lortab/Vicoden/Norco – for mild to moderate pain (hydrocodone +
acetameinophen)
 Tussionex – for coughs (hydrophone + chlorpeniramine)
• Indications:
•
•
Relieve mild to moderate pain and cough
Cough suppressant
–
•
Combined with antihistamines and nasal decongestants
Analgesic effect similar to codeine
– Is 6X more potent than codeine
•
In the USA must beCOMBINED WITH other drugs:
– For analagesia: acetaminophen, aspirin, or ibuprofen
– For cough: antihistamines, and nasal decongestants
Opioid Antagonist
•
*naloxone (Narcan)
• MOA:
–
BINDS to opioid receptors but DOES NOT ACTIVATE the receptor; onset < 2
minutes
–
Route: Parenteral only
• Indications for use:
– ANTIDOTE to reverse the effects of morphine and morphine
like drugs (opioids)
• Respiratory depression - physical stimulation unsuccessful
• Pinpoint pupils shallow/< 8 breaths/min)
• Decreased LOC
MOA: Narcan – a mu antagonist
it binds to the receptor and BLOCKS the response of the opioid
Inhaled Naloxone/Narcan
Stops heroin and other opioid substances from reaching the brain
Dr. Wermeling, a pharmacy professor at the University of Kentucky developed this nasal spray form of
naloxone/Narcan
to help in the treatment of potentially fatal drug overdoses from heroin and other opioid substances.
On the fast track for approval from the FDA
Opioid Antagonists:
Something to consider…
– You totally, instantly, take away their
analgesia
– ½ life of Narcan is only 60 minutes
– Could slip back into respiratory depression
ATYPICAL non-opioid centrally acting
tramadol/Ultram
analgesic:
• Ultram is an non-opioid analgesic
• Former NOT a controlled substance
• Now a Schedule IV (6/2014) d/t increasing recognition of potential for abuse
•
Indications:
–
–
Moderate to severe pain
PO agent
MOA:
– Binds weakly to the mu opioid receptor
– Relieves pain through weak agonist activity at mu opioid receptors
– Inhibits the uptake of serotonin and norepinephrine
Adverse Effects:
Rarely any serious AE
Sedation, dizziness, h/a, dry mouth, constipation
Rare: Seizures; can be fatal when combined with other CNS depressants
Adjuvants: gabapentin/Neurontin
and pregablin/Lyrica
 Classification:
 anticonvulsant
 Indications
◦ To COMPLEMENT the
effects of opioids
◦ Used specifically for
neuropathic pain
1.
2.
3.
enhance analgesia from
opioids
help mange concurrent
symptoms that exacerbate
pain
treat SE of opioids
• MOA
– thought to spontaneously
suppress neuronal firing
• Side Effects
– drowsiness, dizziness,
visual problems
– Only partial reversal
with Narcan
NON-OPIOID Analagesics
• NSAIDS
– Non-steroidal anti-inflammatory drugs
• Nonselective COX inhibitors
• Selective COX-2 inhibitors
• acetaminophen/Tylenol
– not a “TRUE” NSAID
– no anti-inflammatory properties
Non-opioid Analgesics/NSAIDS:
• acetylsalicylic acid
(ASA)  prototype SALICYLATE & NSAID:
–
With caffeine (Excedrin)
–
With antacids (Ascription, Bufferin)
–
Enteric-coated (Ecotrin)
• ibuprofen (Advil, Motrin)
• naproxen/Aleve,Naprosyn – the NSAID that is the hardest
on the kidneys
•
ketorolac/Toradol – PARENTERAL (IM/IV) NSAID
•
celecoxib/Celebrex – COX-2 selective NSAID
– Little inhibition of COX-1 so less GI problems
Indications and MOA of NSAIDS
• Indications:
– mild to mod pain
– inflammation
– fever
– prevention of heart attack
and stroke (ASA only)
• MOA:
– Block a key enzyme of
inflammation -
cyclooxygenase
• Cyclooxygenase converts
arachidonic acid to
prostaglandins and
leukotrienes
• PROSTAGLANDINS CAUSE
INFLAMMATION
• There are 2 types of
cyclooxygenase
– COX-1
– COX-2
NSAIDS BLOCK PROSTAGLANDINS
COMMON SIDE EFFECTS OF NSAIDS
• Non-selective COX inhibitors
(inhibit BOTH COX-1/COX-2)
– ASA, ibuprofen, naproxen
• GI upset,stomach ulcers, GI
bleeding
• n-v-d
• constipation
• rash
• edema – kidney failure
• SOA in some- asthma
• SELECTIVE COX-2 inhibitors:
– celecoxib/Celebrex
• less problems with GI
• does not interfere with
clotting
• can cause serious
cardiovascular thrombotic
events – BLACK BOX
WARNING
BLACK BOX Warning for NSAIDS Serious Side Effects!
Cardiovascular Risk:
NSAIDs may cause an increased risk
of serious cardiovascular thrombotic events, myocardial infarction,
and stroke, which can be fatal. This risk may increase with duration
of use. Patients with cardiovascular disease or risk factors for
cardiovascular disease may be at greater risk."
Gastrointestinal Risk:
NSAIDs cause an
increased risk of serious gastrointestinal adverse events
including bleeding, ulceration, and perforation of the
stomach or intestines, which can be fatal. These events
can occur at any time during use and without warning
symptoms. Elderly patients are at greater risk for serious
gastrointestinal events."
SE UNIQUE to the NSAID Aspirin
• Reye’s Syndrome
• Salicylate poisoning/toxicity
–
Acute
• n/v
• seizures, cerebral edema
– Chronic
• n/v
• TINNUITUS – ringing in the ears
• hearing loss
No Aspirin
for kids!!!
What is Reye’s Syndrome
– Reye’s Syndrome:
• A rare life-threatening illness that can
affect the brain and liver
• Occurs in children < 15 who have been
given ASA to treat a viral infection
– Can cause brain and liver damage – high mortality
rate
– NEVER GIVE ASA FOR ANY REASON IN
TREATING CHILDREN WITH VIRAL
INFECTIONS –use Tylenol and ibuprofen instead
Injectable NSAID: ketolorac/Toradol
• The most potent
NSAID
• INDICATIONS: Toradol is used
to treat acute/SHORT TERM
moderate to severe pain
– Primarily POST-OP pain. Five
days or less
• Given parenterally: IM or IV
–
TORADOL PROVIDES POWERFUL
ANALGESIA WITH MINIMUM
ANTI-INFLAMMATORY ACTION
– Analagesic effect similar
to morphine
• MOA:
• Without the respiratory
depression
suppresses prostaglandin
synthesis
• SE:
•
similar to all NSAIDS
Increase GI ulcers with extended
use.
Nonopioid Analgesics:
acetaminophen/Tylenol
• MOA:
– unknown; prostaglandin synthesis in the CNS?
– Ø anti-inflammatory properties
• Not a true NSAID!
• Indications for use:
– Mild to moderate pain
– (Also fever)
• Limitation:
– Does have a ceiling effect
Nonopioid Analgesics:
acetaminophen/Tylenol
 Adverse effects:
◦ Large amounts (acute)  hepatic necrosis
 Ceiling effect: Adult: do not
exceed 4g/day!
◦ Large amounts (long-term)  liver failure
and nephropathy
 Antidote:
 *acetylcysteine (Mucomyst)
Remember, too much
Tylenol can kill your LIVER!
Healthy liver
Liver after Tylenol OD
Advantages of Tylenol
• Rarely causes GI upset
– May take anticoagulants concurrently
• Kids may take with colds/viral illnesses
• (NOT associated with Reye’s Syndrome)
Nonopioid Analgesics/NSAIDS –
Pearls for Practice
• Can alternate true NSAIDs with acetaminophen
(different MOA’s)
• Good to give in conjunction with opioids for moderate to
severe pain
– If giving with “Percocet, be careful not to supplement with
acetaminophen – want to protect that liver! (true NSAID is
better choice)
• Choose true NSAID’s (not Tylenol) if inflammation is the
causative factor