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Pain and Inflammation:
Afferent and Efferent Nervous System
Responses
1
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Pain
• The physiologic mechanisms involved in the
pain response are complex.
• The sensation of peripheral pain begins in
afferent neurons called nociceptors.
• These receptors are activated by chemical
mediators, such as prostaglandins,
histamine, bradykinin, and serotonin.
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Pain
• Pain is a multidimensional,
subjective experience.
• Studies indicate health care
providers undertreat pain
in acute care settings for
fear of causing addiction.
• Pain is a major indication
for drug therapy.
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Physiology
The Peripheral
nervous system (PNS)
and Central nervous
(CNS) are an
integrated system that
provides a pathway
for pain transmission.
Pain receptors are found on the end plates of
afferent neurons.
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Things that Influence Pain
• Pain has both physical and emotional components.
• How pain is perceived affects pain’s location,
intensity, and quality.
Some individuals are hyper-sensitive to nerve
impulses
Reduce perception, you can reduce pain.
• Stimulation of the limbic system produces the
emotional response to the physical stimulus of
pain.
• The limbic system is responsible for emotional
arousal, anxiety, fight-or-flight response, etc.
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• Nociceptic pain is caused by
the activation of the delta
and C nociceptors in
response to painful stimuli,
such as injury.
• Neuropathic pain is the
term used to represent pain
in which the underlying
pathology is abnormal
processing of stimuli in the
peripheral or central
nervous systems.
Types of Pain
• Acute pain, meaning
the immediate phase
of response to an
insult or injury,
results from tissue
damage.
• Chronic pain may
persist well beyond
actual tissue injury
and healing.
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Pain
Rating
Tools
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Medications to
Treat Severe Pain
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Narcotic Analgesics
• Narcotics have an important role in pain management
and control.
• Narcotics are required for conditions that have
moderate-to-severe pain.
• The narcotic analgesics include opiate agonists, mixed
agonist-antagonists, and antagonists based on their
activity at opioid receptors.
Prototype drug:
morphine (MS Contin)
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Morphine: Core Drug Knowledge
• Pharmacotherapeutics
• Moderate-to-severe acute or chronic pain
• Pharmacokinetics
• Metabolism: liver. Onset: 15 to 30 minutes.
Duration: 3 to 7 hours.
• Pharmacodynamics
• Agonist at several opiate receptors in the
central and peripheral nervous system.
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Morphine: Core Drug Knowledge
• Contraindications and precautions
• Respiratory conditions
• Side effects – cholinergic and histaminergic
• Sedation
• Constipation
• Urinary retention
• Adverse effects
• Respiratory depression or arrest, circulatory
depression, cardiac arrest, shock, and coma
• Tolerance & Dependency
• Withdrawal Syndrome
• Drug interactions
• Multiple drug interactions
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Morphine: Planning and
Interventions
• Maximizing therapeutic effects
• Assess pain prior to and during therapy
• Use a pain assessment tool
• Minimizing adverse effects
• Conduct frequent assessment especially for
respirations
• Provide additional pain medication for
breakthrough pain
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Mild Opioid Agonists
• The mild opioid agonists include codeine,
hydrocodone and oxycodone.
• Examples:
• Tylenol #3, Codeine cough syrup
• Norco, Lortab (Hydrocodone +
acetominophen 325 mg or 500 mg)
• Percocet (Oxycodone + acetominophen)
Prototype drug:
Hydrocodone/acetominophen (Norco)
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Hydrocodone/acetominophen (Norco) :
Core Drug Knowledge
• Pharmacotherapeutics
• Treat mild-to-moderate pain
• Pharmacokinetics
• Absorbed from GI tract, peaks in 1 to 2 hours;
crosses the placenta and secreted in breast
milk
• Pharmacodynamics
• Acts at specific opioid receptors in the CNS to
produce analgesia, euphoria, and sedation
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Hydrocodone/acetominophen (Norco) :
Core Drug Knowledge
• Contraindications and precautions
• Not given with other narcotics
• Side effects – cholinergic and histaminergic
• Drowsiness, sedation, dry mouth, nausea and
vomiting, and constipation
• Adverse Effects
• Respiratory depression
• Tolerance and dependency
• Withdrawal syndrome
• Drug interactions
• Other sedating medications and alcohol
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Hydrocodone/acetominophen (Norco) :
Planning and Interventions
• Maximizing therapeutic effects
• Actions are similar to those for morphine.
• Minimizing adverse effects
• Provide for patient safety
• Assess respiratory function prior to
administration
• Do not administer to patients who need to cough
to clear airway.
• Contraindicated in emphysema, chronic
obstructive pulmonary disease (COPD)
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Drugs that Treat Mild to
Moderate Pain, Fever,
Inflammation, and
Migraine Headache
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Prostaglandins
• Prostaglandins come from arachidonic acid, which
is released from cell membranes in response to
physical, chemical, hormonal, bacterial, or other
stimuli.
• Cyclooxygenase (COX) enzymes convert the
arachidonic acid to prostaglandin.
Prostaglandins modulate some of
inflammation, body temperature, pain
transmission, and platelet aggregation.
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Prostaglandin Synthesis - Review
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Fever - Physiology
• Temperature regulation is a function of the
hypothalamus.
• Fever is the result of fever-inducing substances
called pyrogens generated by the body in response
to infection and some other causes.
• Bacteria and viruses are less likely to survive in a hot
environment
• Fever causes activation of white blood cells that
secrete cytokines.
• Cytokines increase the synthesis and secretion of
the hormone prostaglandin in the hypothalamus.
Prostaglandin causes the hypothalamus to
reset (raise or lower) the body temperature.
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Inflammation - Physiology
• Numerous types of stimuli cause an
inflammatory response in the body.
• The classic signs of inflammation are:
• Swelling (edema)
• Heat
• Redness
• Pain
• Loss of function
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Inflammation (cont.)
• Acute inflammation is divided into vascular and
cellular responses.
• The vascular response occurs almost immediately
after the injury.
Video – Acute Inflammation:
http://www.youtube.com/watch?v=suCKm97yvyk
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Platelet Aggregation
• Platelet aggregation is the clumping together of
platelets in the blood.
• Platelet aggregation can be a beneficial process.
• An early step in wound healing
• Platelet aggregation can also be harmful. It is the
first step in a sequence of events that leads to the
formation of a thrombus.
Prostaglandins increase
platelet aggregation
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Prostaglandin-related Drugs
• Drugs work by reducing prostaglandin
synthesis or by blocking the effects of the
COX enzyme.
• The result is less fever, pain, inflammation
and slowed blood clotting.
• Drugs vary in how much they effect each
of these outcomes.
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Drug Categories that Treat Mild to Moderate Pain
Drug Category
Treats Mild to
Moderate Pain
Reduces
Inflammation
COX Enzyme inhibitor:
celecoxib (Celebrex)
Yes
Yes
Salicylates: aspirin
Yes
Yes
Non-steroidal Antiinflammatory Drugs
(NSAIDS): ibuprofen (Advil)
Yes
Yes
Para-aminophenol Drug:
Yes
acetominophen (Tylenol)
paracemetol Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
No
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cyclooxygenase (COX) Enzymes
• There are two forms of the COX enzyme:
COX-1 and COX-2.
• COX-1 synthesizes prostaglandins that are
involved in the regulation of normal cell
activity.
• COX-2 appears to produce prostaglandins
mainly at sites of inflammation.
COX-2 Enzyme Inhibitor Prototype Drug:
celecoxib (Celebrex)
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Drugs to Treat Inflammation and Fever
• Salicylates and non-steroidal analgesic drugs
(NSAIDs) are used to treat inflammation and fever
in a variety of conditions.
• Salicylates are used in managing conditions ranging
from a simple headache to acute myocardial
infarction (MI).
• NSAIDs are used primarily as anti-inflammatory
drugs but are also used extensively as analgesics.
Prototype drug: acetyl-salicylic acid or ASA,
Aspirin (Bayer)
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Aspirin: Core Drug Knowledge
• Pharmacotherapeutics
• Treat mild-to-moderate pain
• Prevent platelet aggregation
• Pharmacokinetics
• Absorbed in the stomach and small intestines;
• Highly protein bound
• Pharmacodynamics
• Fever: inhibited prostaglandin synthesis in the
hypothalamus
• Inflammation: peripheral inhibition of prostaglandin
• Antiplatelet: irreversible inhibition of thromboxane
A2
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Aspirin: Core Drug Knowledge
• Contraindications and precautions
• Peptic ulcer disease, or bleeding disorders, and
• Children with febrile illnesses
• Side effects
• Nausea & vomiting
• Adverse effects
• Renal failure, abnormal bleeding
• Ototoxicity with long-term use
• Drug interactions
• Other drugs that are highly protein bound
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Aspirin: Planning and Interventions
• Maximizing therapeutic effects
• Give with milk or food to decrease
GI upset.
• Minimizing adverse effects
• Do not administer aspirin to a patient with a
medical condition that contraindicates its use.
• Monitor patients for signs of bleeding
•
•
•
•
Black tarry stools
Blood in the emesis
Diarrhea with blood in it
Multiple Bruises
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Nonsteroidal Anti-Inflammatory Drugs
The NSAIDs are grouped by chemical classes (many
NSAIDS exist).
• NSAIDs all inhibit COX and prostaglandin synthesis.
• All NSAIDs carry a Black Box warning stating that
they increase the risk of MI and stroke.
Prototype drug: ibuprofen
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Ibuprofen: Core Drug Knowledge
• Pharmacotherapeutics
• Arthritis, mild-to-moderate pain, primary
dysmenorrhea, migraine headache, and fever
• Pharmacokinetics
• Absorbed from the GI system. Peak: 1 to 2
hours. Highly protein bound and is
metabolized in the liver
• Pharmacodynamics
• Inhibited synthesis or release of prostaglandins
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Ibuprofen: Core Drug Knowledge
• Contraindications and precautions
• GI disease
• Side effects
• Nausea & vomiting
• Some risk of BP elevations
• Adverse effects
• GI upset and bleeding,
• Hepatotoxicity,
• Acute renal failure.
• Increases risk of CVA or MI with prolonged use.
• Drug interactions
• Similar to those of salicylates
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Ibuprofen: Planning and Interventions
• Maximizing therapeutic effects
• Give ibuprofen with milk or food to
decrease gastric distress.
• Minimizing adverse effects
• Closely monitor patients with pre-existing
medical conditions or drug therapy that may
interact with ibuprofen.
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Para-Aminophenol Derivatives
• There is only one drug in this category.
• It works by slowing the production of
prostaglandins.
Prototype drug: acetaminophen (Tylenol)
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Acetaminophen: Core Drug
Knowledge
• Pharmacotherapeutics
• Used to treat fever or mild pain
• Pharmacokinetics
• Administered orally. Absorbed: GI tract. Peak: 60
minutes. T1/2: 1 to 3.5 hours
• Pharmacodynamics
• Primarily centrally acting; inhibits prostaglandin
synthesis in the CNS
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Acetaminophen: Core Drug Knowledge
• Contraindications and precautions
• Hepatic disease, viral hepatitis, or alcoholism
• Side effects
• Generally well tolerated. Elderly occasional report
sleepiness
• Adverse effects
• Overdose of medication can be fatal (liver failure)
• Drug interactions
• Activated charcoal – used to reverse overdosage
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Acetaminophen: Planning and
Interventions
• Maximizing therapeutic effects
• Acetaminophen can be administered without
regard to meals.
• Minimizing adverse effects
• Assess patients for medical conditions that
contradict the use of acetaminophen (liver).
• Periodic CBC, platelet count, and liver and renal
function tests for patients on long-term therapy.
Maximum safe daily dosage 3000 mg/24
hours
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Corticosteroids
• Glucocorticoids are hormones of the endocrine
system.
• They are produced by the cortex of the adrenal
glands (adrenal glands are located at the top of
each kidney).
• The primary glucocorticoids produced by the
adrenal gland are cortisol (hydrocortisone) and
cortisone.
• Glucocorticoids suppress immune system
responses and reduce inflammation.
Prototype drug: prednisone (Deltasone)
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Prednisone: Core Drug Knowledge
• Pharmacotherapeutics
• Anti-inflammatory and immunosuppressive
effects
• Pharmacokinetics
• Absorbed from GI tract. Metabolized: liver.
Excreted: urine.
• Pharmacodynamics
• Primarily glucocorticoid activity, although some
mineralocorticoid activity is present and more
apparent when the drug is administered in high
doses
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Prednisone: Core Drug Knowledge
• Contraindications and precautions
• Systemic fungal infections
• Side effects
• Anxiety, mood swings, insomnia, headache, GI
complaints, menstrual irregularities,
hyperglycemia
• Adverse effects
• Agitation, psychosis, depression
• Abrupt discontinuation of a glucocorticoid
following prolonged administration may result in
acute adrenal insufficiency.
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Prednisone: Planning and
Interventions
• Maximizing therapeutic effects
• The best time for administration of doses of
glucocorticoids is early in the morning in order
to mimic the natural body.
• Minimizing adverse effects
• Monitor the patient, especially the surgical
patient, carefully for signs of infection.
• Administration can lead to peptic ulcer
disease.
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Serotonin-Selective Drugs
• Serotonin-selective drugs are used to relieve pain
and inflammation related to migraine headache.
• They are not useful for other types of headache or
inflammation that occur elsewhere in the body.
• These drugs are also known as “triptans” because
the generic name of these drugs ends as such.
• The triptans are considered first-line drugs for the
treatment of acute migraine headache.
Prototype drug: sumatriptan (Imitrex)*
*not on drug list
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Sumatriptan: Planning and
Interventions
• Maximizing therapeutic effects
• Confirm diagnosis of type of headache the
patient is having.
• Administer drug as soon as headache begins.
• Minimizing adverse effects
• Assess the patient for a history of cardiovascular
or cerebrovascular disorder.
• After administering sumatriptan, monitor for
signs and symptoms of vasospasm and allergy.
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Adjuvant Medications for Pain
• Adjuvant Medications are used with a primary pain
medication to increase pain relief in order to reduce
the dosage of the primary medication.
• Typical Adjuvants:
• Antihistamines
• Anticonvulsants
• Antidepressants
• Glucocorticoids (steroids)
• Combining mild analgesics with opioids (e.g.
hydrocodone/acetominophen [Norco])
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Challenge Questions
When administering morphine, the most important
things for the nurse to assess are:
A. Pain level
B. Respiratory rate
C. Blood Pressure
D. Both A and B
C. All of the above
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Challenge Questions
When administering morphine, the most important
things for the nurse to assess are:
D. Both A and B
Rationale: The nurse should always assess
the level of pain the patient is experiencing
prior to administration of morphine. Also
morphine can cause significant respiratory
depression, so respiratory rate should also
be assessed.
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Challenge Questions
Why is aspirin contraindicated in children with
varicella (Chicken Pox)?
A. Can cause bleeding from skin lesions
B. Will decrease effectiveness of antibiotic
therapy
C. Can cause increased fever
D. Can cause Reye syndrome
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Challenge Questions
Why is aspirin contraindicated in children with
varicella (Chicken Pox)?
D. Can cause Reye syndrome
Rationale: Aspirin is contraindicated in children
with varicella or flu-like illness because it is
associated with the occurrence of Reye syndrome.
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Reye’s Syndrome
• Reye's syndrome is a rapidly progressive disorder that
usually begins shortly after recovery from an acute viral
illness, especially influenza and varicella (chickenpox).
• The classic features are a rash, vomiting, and liver damage.
• It is a potentially fatal syndrome that has numerous
detrimental effects on many organs, especially
the brain and liver
• The exact cause is unknown and, while it has been
associated with aspirin consumption by children with viral
illness, it also occurs in the absence of aspirin use.
• The disease causes fatty liver and cerebral edema (swelling
of the brain).
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Challenge Questions
Why were all NSAIDs given a Black Box warning by
the FDA?
A. Risk of MI and CVA is increased with use of
NSAIDs.
B. Risk of GI bleeding is increased with use of
NSAIDs.
C. NSAIDs can cause kidney failure.
D. NSAIDs can cause hepatic failure.
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Challenge Questions
Why were all NSAIDs given a Black Box warning by
the FDA?
A. Risk of MI and CVA is increased with use
of NSAIDs.
Rationale: All NSAIDs have a risk of causing MI or
CVA; the risk increases with prolonged use of the
medication.
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Challenge Questions
In which of the following patients is
acetominophen (Tylenol) contraindicated?
A. 25 year old with headache
B. 45 year old with GI bleeding
C. 52 year old with hepatitis C
D. 62 year old with osteoarthritis
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Challenge Questions
In which of the following patients is
acetominophen (Tylenol) contraindicated?
C. 52 year old with hepatitis C
Rationale: Acetominophen is contraindicated
in patients with impaired liver/hepatic
function.
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Challenge Questions
Where are the adrenal glands located?
A. Brain
B. Pancreas
C. Liver
D. Kidneys
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Challenge Questions
Where are the adrenal glands located?
D. Kidneys
Rationale: The adrenal glands are located on top of
the kidneys.
Their role is to: 1) excrete chemicals that trigger the
sympathetic nervous system (epinephrine); 2) release
glucocorticoids that are involved with inflammation
and immune response (cortisone); and, 3) release
mineralocorticoids that are involved with fluid
balance.
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Acetaminophen (Tylenol)
Aspirin
Ibuprofen
Reduces fever
Relieves mild pain
Reduces fever
Reduces inflammation
Relieves mild pain
Reduces platelet aggregation
Celecoxib (Celebrex)
Morphine
Hydrocodone/
acetominophen (Norco)
Codeine
Reduces fever
Reduces inflammation
Relieves mild pain
Relieves moderate to
severe pain
Potentially Addictive
Suppresses respirations
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Case Study – Application
Margaret is a 72-year old woman with rheumatoid arthritis
and peptic ulcer disease. She has normal hepatic and renal
functioning but some mild hearing loss.
1. Which medication may be most appropriate for her to
take on a routine basis to reduce the inflammation
from her arthritis and treat her pain?
2. Which medications are contraindicated or should be
used with extreme caution?
3. If she has a bout of severe pain, how might this be
managed?
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