Inflammation: Causes, Phases & Mediators

Inflammation

• Causes include trauma, surgery, extreme heat or cold, caustic chemical agents, or infection.
• It is a protective response using chemical mediators to neutralize harmful agents causing tissue injury.
• Chemical mediators include prostaglandins, histamines, and kinins.

Pathophysiology:

• Includes inflammatory phases

Vascular Phase:

• Occurs 10–15 minutes after an injury.
• Associated with vasodilation and increased capillary permeability.
• Fluid and blood substances move to the injured site.

Delayed Phase:

• Is when leukocytes infiltrate inflamed tissue.

Cyclooxygenase (COX) Enzyme:

• Converts arachidonic acid into prostaglandins.
• Has two enzyme forms.
  • COX-1 protects the stomach lining and regulates blood platelets.
  • COX-2 triggers inflammation and pain.

Cardinal Signs of Inflammation:

• Redness occurs because blood accumulates in the area of tissue injury due to the release of the body's chemical mediators (kinins, prostaglandins, and histamine), which dilate the arterioles.
• Edema/Swelling occurs as plasma leaks into the interstitial tissue at the injury site because kinins and histamine increase capillary permeability.
• Heat is caused by increased blood accumulation and pyrogens interfering with the temperature-regulating center in the hypothalamus.
• Pain arises from tissue swelling and the release of chemical mediators.
• Loss of function results from fluid accumulation at the tissue injury site and pain, which decreases mobility.

Antiinflammatory Drug Groups

• Nonsteroidal antiinflammatory drugs (NSAIDs)
• Corticosteroids
• Disease-modifying antirheumatic drugs
• Antigout drugs

NSAID Actions

• Inhibit the biosynthesis of prostaglandins.
• Relieve pain.
• Reduce elevated body temperature.
• Inhibit platelet aggregation.
• Mimic the effects of corticosteroids.
• Inhibit the COX enzyme needed for prostaglandin biosynthesis.
• Inhibit enzyme cyclooxygenase (COX).

NSAID Classifications

First-Generation NSAIDs:

• Salicylates like Aspirin
• Propionic acid derivatives like Ibuprofen and Naproxen

Second-Generation NSAIDs:

• Selective COX-2 inhibitors

Aspirin

• The actions are anti-inflammatory, antiplatelet, and antipyretic.
• A toxic serum salicylate level would be greater than 300 mcg/mL.
• Drug-lab-food interactions can increased bleeding with anticoagulants and other NSAIDs, increase risk for hypoglycemia with oral antidiabetics, increase the risk for gastric ulcers with glucocorticoids, and decrease the effects of ACE inhibitors as well as loop diuretics .
• Lab interactions: increased PT, bleeding time, INR, and uric acid, and decreased cholesterol, T3 and T4 levels, and K.
• Foods containing salicylates include prunes, raisins, licorice, and certain spices like curry and paprika.
• Caution:
  • Avoid taking with other NSAIDs
  • Avoid during the last trimester of pregnancy
  • Do not give to children with flu or virus symptoms because of the risk of Reye syndrome.
• Side effects/adverse reactions: dizziness, lethargy, headache, confusion, agitation, diaphoresis, dehydration, Gl distress, ulceration, bleeding, seizures, tinnitus, hearing loss, and Reye syndrome.

Clinical Judgment: Salicylate

• Recognize cues by looking at patient's medical and drug history
• Analyze cues and prioritize hypothesis by listing, acute pain, injury, and nausea
• Generate Solutions: Patient's may experience reduced swelling and redness in 1 week
• Take Action:
  • Warn patients not to give aspirin for virus or flu symptoms to children to avoid the risk of Reye syndrome.
  • Educate parents to call the poison control center immediately if a child has taken a large or unknown amount of aspirin.
  • Inform patients that aspirin tablets can cause Gl distress.
• Evaluate Outcomes

Ibuprofen

• Ibuprofen is the most widely used NSAID.
• It inhibits COX 1 and COX 2.
• The common uses are rheumatoid arthritis, osteoarthritis, and pain.
• Side effects/Adverse effects: drowsiness, dizziness, headache, confusion, insomnia, dreams, blurred vision, tinnitus, gastric distress and bleeding, and edema.
• Drug interactions can lead to increased bleeding with warfarin, increased effects with phenytoin, sulfonamides, and warfarin, and a decreased effect with aspirin.
• If the over-the-counter effectiveness of regular dose (200-400 mg) is not effective, the patient should consult their physician before increasing the dose, as they may need a prescription (NSAID).
• It may take several weeks to reach a therapeutic effect when taking it for chronic pain, such as arthritis.

Clinical Judgment: Ibuprofen

• Take action:
  • observe patients for bleeding gums, petechiae, ecchymoses, or black tarry stools.
  • Report Gl discomfort
  • Advise patients to avoid alcohol while taking NSAIDs.
  • Alert patients that many complementary and alternative therapies may interact with NSAIDs and could cause bleeding.
• Evaluate Outcomes

Selective Cox-2 Inhibitors: Celecoxib

• Selectively inhibits COX-2 enzyme without inhibition of COX-1.
• Uses include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain, and dysmenorrhea.
• A similar agent is Meloxicam.
• Side effects: dizziness, headache, sinusitis, Gl distress, ulceration, obstruction/perforation, peripheral edema, and hypertension.

NSAIDs in Older Adults:

• Drug interactions are more common due to the number of drugs taken.
• There is a greater incidence of Gl distress and ulceration.
• Reduce dose decreases the risk of side effects.
• It is important to increase fluid intake for adequate hydration.

Corticosteroids

• Action: controls inflammation by suppressing or preventing many components of the inflammatory process at the injured site.
• Use: not the drug of choice for arthritis because of side effects but commonly used for arthritic flare-ups.
• Discontinuation: when discontinuing long-term steroid therapy, the dosage should be tapered over 5–10 days.

Pain Terminology

• Pain is the fifth vital sign, so nurses assess it regularly.
• Most common classification is by duration.
  • Acute pain can be mild, moderate, or severe and is associated with a specific tissue injury, sudden onset and <3 months duration
  • Chronic pain usually has a vague origin and gradual onset with a duration of >3 months
• May be classified by origin
  • Nociceptors (sensory receptors for pain) are triggered by a mechanical, thermal, or chemical stimuli in peripheral tissue.

Other Pain Terminology

• Pain threshold reflects level of stimulus needed to create a painful sensation.
• Pain tolerance indicates the amount of pain someone can endure without it interfering with normal functioning.
• Analgesics: opioid and nonopioid and are prescribed for the relief of pain The choice of analgesic depends on the severity of pain.
  • Nonopioid is AKA nonnarcotic, used for mild to moderate pain
  • Opioid is AKA narcotic, used for moderate to severe pain.

Types of Pain

• Acute
• Chronic
• Cancer: occurs from pressure on nerves and organs, blockage to blood supply, or metastasis to the bone.
• Neuropathic: unusual sensory disturbance that involves neural supersensitivity or a disease to the peripheral or central nervous system.
• Somatic: comes from structural tissues such as bones and muscles.
• Superficial: located on the surface area such as skin and mucous membranes.
• Vascular: occurs from vascular or perivascular tissue, contributing to headaches or migraines.
• Visceral: originates in organs.

Nonopioid Analgesics:

• Less potent than opioids
• Used for mild to moderate pain
• Effective for dull throbbing pain
• Treats headaches, minor abrasions
• reduces inflammation, muscular aches
• Helps mild to moderate arthritis
• Examples: NSAIDS, Acetaminophen

Acetaminophen

• Not an NSAID.
• Can be used for mild pain (rated 1-3).
• Inhibits prostaglandin synthesis.
• Uses: muscular aches and pain, fever.
• Maximum dose: 4g/day (can take 2 325 mg tabs 6x per day), or if taken frequently, 2g/day.
• Side effects: anxiety, headache, insomnia, fatigue, constipation, peripheral edema, and low incidence of Gl distress.
• Toxic effects/excess dosing: hepatic/renal failure and hearing loss.

Clinical Judgment: Acetaminophen

• Recognize cues by ascertaining pain severity or a history of liver dysfunction
• Analyze cues and prioritize hypothesis, look for acute pain, injury, discomfort, and decreased mobility
• Generate solutions: The patient will report that pain has decreased within 1 hour after acetaminophen administration
• Take Action:
  • Check results from liver enzyme tests
  • Teach patients to:
    • Keep acetaminophen out of children's reach
    • Avoid alcohol
    • Report side effects
  • Check if serum acetaminophen level if toxicity is suspected.
• Evaluate Outcomes

Opioid Analgesics

• Use: moderate and severe pain; antitussive and antidiarrheal effects
• Action site: acts on the CNS
  • it suppresses pain impulses, along with respiration and coughing
• The Side effects/adverse effects: N/V, constipation, urinary retention, orthostatic hypotension, respiratory depression, and dizziness.

Morphine

• Used to treat acute pain, dyspnea, and relieve anxiety preoperatively
• Side effects/adverse reactions:
  • Drowsiness, dizziness, and blurred vision
  • Miosis (excessive constriction of the pupil), orthostatic hypotension
  • Dyspnea, dependence
  • GI distress, flatulence, constipation
  • Urinary retention and respiratory depression
• Naloxone is an antidote

Clinical Judgement

• Recognize cues by determining drug history and doing allergy check and assess type. location, and duration of patients
• Analyze cues and prioritize hypothesis by paying mind to, acute pain and decreased gas exchange
• Generate solutions: The patient will report pain has decreased.
• Take action:
  • Administer morphine before pain reaches its peak to maximize drug effectiveness.
  • Monitor vital signs frequently to detect respiratory changes.
  • Check pupil changes and reaction.
  • Naloxone should be available as an antidote to reverse respiratory depression if morphine overdose occurs.
• Evaluate Outcomes

Meperidine (Demerol)

• Primarily effective in Gl procedures
• It’s preferred to morphine during pregnancy
• Caution with large doses in older adults and patients with advanced cancer
• Causes Neurotoxicity that leads to nervousness, agitation, irritability, tremors, seizures
• Common side effects are Dizziness, drowsiness, euphoria, confusion Constipation, dependence
• There is Less constipation and urinary retention than morphine

Hydromorphone (Dilaudid)

• Has a Analgesic effect is approximately six times more potent than morphine
• Side effects and adverse reactions -Dizziness, drowsiness, confusion, miosis -Orthostatic hypotension, weakness
• Constipation, urinary retention
• Tolerance, dependence -Respiratory depression
• Less hypnotic effects and Gl distress than morphine

Patient-Controlled Analgesia (PCA)

• Used by patients needing to take medication like, morphine, fentanyl, and hydromorphone.

Loading Dose:

• A dose given initially to achieve pain relief in a dose of 2-10 mg with morphine
• The amount of medication the patient is able to receive with each does is determined by the Predetermined Safety Limits (push of button)
• Lockout Mechanism: an electric control that prevents the patient from administering doses to close together and prevents overdoses

Transdermal Opioid Analgesics

• Provides continuous pain control and gives patients fentanyl
• Is helpful for chronic pain
• Available in various strengths
• Titration
  • Downward over time postoperative
  • Upward for cancer pain relief

Analgesics in Special Populations

Children

• Difficult to assess pain due to communication issues and fears, but nurses can use WongBaker faces scale or Faces Legs, Activity, Cry, Consolability (FLACC) depending on child's age.
• Oral liquid medication for pain is best

Older Adults:

• Adults aged 65+ may need adjusted drug doses to avoid side effects.
• More prone to polypharmacy
• Liver and renal functions decrease drug excretion, causing drug accumulation.
• There's decreased cognitive and sensory perceptual abilities
• May be unable to report pain.
• Look for physical signs including moans, grimacing, clenched teeth, noisy respirations, and restlessness.

Oncology Patients:

• Cancer pain is managed using the WHO “ladder.”
  • Step 1: Nonopioids (Mild analgesia)
  • Step 2: Nonopioids and mild opioids (Moderate analgesia)
  • Step 3: Stronger opioids (Severe analgesia)
• Opioids are titrated until pain relief is achieved.
• No set dosage limits.

Individuals with Substance Abuse History:

• Opioids are safe, even though they may need larger doses.
• Avoid opioid agonist-antagonists because they may cause withdrawal.
• Addiction is psychologic and physical dependence after prolonged use.

Adjuvant Therapies

• Developed for other reasons but found effective for pain relief.
• Therapy often includes, anticonvulsants, antidepressants, corticosteroids, antidysrhythmics, and local anesthetics
• Antiseizure medications (gabapentin) are used for neuropathic pain and migraine prevention.
• Lower doses of tricyclic antidepressants (TCAs) treat peripheral neuropathy effectively.
• Corticosteroids can reduce nociceptive stimuli.
• Antidysrhythmics (mexiletine) block sodium channels to reduce pain.
• A local anesthetics (lidocaine patch) interrupts pain signals to the brain.
• Adjuvant medications increase the effectiveness of opioid analgesia for persistent pain
• Reduce adverse effects

Opioid Antagonist

• Antidotes drug toxicity of natural and synthetic opioid analgesics.
• Opioid antagonists displace opioids by blocking the receptor
• Indications for opioid antagonists include reversal of postoperative opioid depression and opioid overdose.
• Naloxone is administered IM, IV, or by inhalation, while naltrexone hydrochloride is administered orally
• Reverses respiratory and CNS depression
• Patients should be monitored as they might still action, and further analgesia may be needed.
• Closely monitor indication of analgesic such as tachycardia, nausea, and vomiting, and the possible need for further analgesia.
• The patient should be evaluated for bleeding because cause an elevated PTT