NURS 333 Pharmacology in Nursing - Inflammation and Analgesics

Inflammation

• Body's response to tissue injury.

• Vascular reaction: Fluid, WBCs, and chemical mediators arrive at the site within 10-15 minutes, causing vasodilation and increased capillary permeability.

• Delayed phase: Arrival of leukocytes.

• Infection: Caused by microorganisms leading to inflammation.

• Cardinal signs of inflammation:

  • Redness.

  • Swelling (edema).

  • Heat.

  • Pain.

  • Loss of function.

• Chemical mediators:

  • Prostaglandins: Cause vasodilation, smooth muscle relaxation, increased capillary permeability, and sensitization to pain.

  • Cyclooxygenase (COX): Enzyme that converts arachidonic acid into prostaglandins.

    • COX-1: Protects stomach lining and regulates platelets.

    • COX-2: Causes inflammation and pain.

Anti-inflammatory Drugs

• Inhibit prostaglandins.

• May also:

  • Relieve pain (analgesic).

  • Reduce fever (antipyretic).

  • Inhibit platelets (anticoagulant).

• Aspirin (ASA) is the oldest.

• Non-steroidal anti-inflammatory drugs (NSAIDS): Mimic corticosteroids but aren't chemically related; frequently used for musculoskeletal (MSK) conditions.

• Not usually recommended for mild headaches; ASA, acetaminophen, or ibuprofen are preferred.

• NSAIDS reduce swelling, pain, and joint stiffness.

• OTC formulations: Ibuprofen, naproxen; all others are prescription (Rx).

• If patient tolerates ASA without gastric upset, ASA products are recommended.

Types of NSAIDS

• 1st Generation:

  • Salicylates

  • Para-chlorobenzoic acid derivatives (indoles)

  • Phenylacetic acids

  • Fenamates

  • Oxicams

• 2nd Generation:

  • Selective COX-2 inhibitors

COX-2 Inhibition

• Triggers pain and inflammation at the site of injury.

• COX-2 Inhibition:

  • Suppresses inflammation.

  • Provides pain relief.

  • Reduces fever.

  • Does not cause gastric ulceration.

  • Has no effect on platelets.

• COX-2 inhibitors:

  • Block only COX-2.

  • Stomach protection remains intact.

  • Example: Celecoxib.

  • Patients at risk for CVA/MI would not benefit from COX-2; must use ASA for prevention of blood clots.

  • May help prevent colon cancer – fruits and vegetables can block the COX-2 enzyme and naturally protect the colon

Aspirin (Acetylsalicylic Acid - ASA)

• Nonselective - COX-1 & COX-2.

• Good absorption via GI tract, wide distribution, renal excretion.

• Pharmacotherapeutics:

  • Suppresses inflammation.

  • Analgesia.

  • Fever reduction.

  • Dysmenorrhea.

  • Suppresses platelet aggregation.

• Onset within 30 minutes, peaks 1-2 hours, duration 4-6 hours, short half-life.

• Side effects: Dizziness, drowsiness, HA, anorexia, N/V/D.

• Contraindications: PUD, bleeding disorders, hypersensitivity, pregnancy (especially last trimester), children with chickenpox or flu.

• Adverse Effects:

  • GI ulceration.

  • Bleeding.

  • Hypersensitivity.

• Life-threatening:

  • Agranulocytosis, hemolytic anemia, leukopenia, anaphylaxis, Reye syndrome, hepatotoxicity, thrombocytopenia.

• Drug Interactions:

  • Warfarin, heparin: ASA intensifies effect.

  • Glucocorticoids: Both promote gastric ulceration.

  • Alcohol: Increases risk of bleeding.

• Labs: monitor:

  • \downarrow potassium, cholesterol, T3, T4.

  • \uparrow bleeding time, uric acid levels.

Para-Chlorobenzoic Acid (Indomethacin)

• Used to treat rheumatoid, gouty, and osteoarthritis, tendinitis, and ankylosing spondylitis.

• Prostaglandin inhibitor, highly protein bound (potential for toxicity).

• Moderate half-life (2.6-11.2 hrs).

• Suppresses inflammation but can cause gastric ulceration (take with food).

• Dosage:

  • PO 25 mg bid/tid, Max 200 mg/day.

  • PO SR 75 mg/day, Max 150 mg/day.

Phenylacetic Acid Derivatives (Diclofenac)

• Used to treat mild to severe pain, rheumatoid/osteoarthritis, and spondylitis.

• Available in oral, XR, and topical forms; half-life is 2 hours.

• Topical has fewer SE, AE.

• Ketorolac:

  • First injectable.

  • Used for short-term pain management (< 5 days).

  • Greater analgesic effect.

  • Oral, IM, IV, intranasal.

  • 30-60 mg IM q6hrs

Proprionic Acid Derivatives (Ibuprofen)

• Used to treat inflammation and pain, and reduce fever.

• Highly protein-bound (potential for toxicity).

• Less severe gastric upset compared to ASA, indomethacin.

• Available OTC 200 mg

• SE: HA, dizzy, anorexia, N/V/D, fluid retention/edema.

• AE: tinnitus, bleeding.

• Life-threatening AE: Anemia, neutropenia, thrombocytopenia, nephrotoxicity, anaphylaxis.

• Drug interactions (avoid):

  • Warfarin.

  • Sulfonamides.

  • Cephalosporins.

  • Phenytoin.

• If taken with insulin/oral hypoglycemic, may cause hypoglycemia; toxicity may occur with calcium channel blocker.

Fenamates (Meclofenamate, Mefenamic acid)

• Treat acute/chronic arthritis.

• Gastric irritation common; don’t use if have PUD.

• SE: edema, dizziness, pruritis, tinnitus.

Oxicams (Piroxicam, meloxicam)

• Treat long-term rheumatoid/osteoarthritis.

• GI distress: ulceration.

• Long half-life; once-a-day dosing.

• Therapeutic level for piroxicam 1-2 weeks.

• Highly protein bound risk for toxicity.

• Do not take with ASA or other NSAIDS.

1st Generation NSAIDS

• GI irritation.

• Sodium and water retention.

• Avoid alcohol.

• When assessing the patient:

  • Determine if taking phenytoin, sulfonamides, warfarin.

  • Hx of renal or liver dz.

  • Hx of GI condition: PUD.

  • Hx of bleeding d/o.

  • Peripheral edema.

Second Generation NSAIDS (Celecoxib/Celebrex)

• Selective inhibition of COX-2.

• Well absorbed.

• Hepatic metabolism, excretion in feces.

• Pharmacotherapeutics:

  • Osteoarthritis.

  • Rheumatoid arthritis.

  • Dosing: PO 100-200 mg once or twice daily.

  • MAX 800 mg/day

• Adverse Effects:

  • Gastric ulceration & bleeding.

  • Edema, HTN.

  • Stroke life-threatening

• Drug Interactions:

  • Warfarin.

  • ACE Inhibitors

NSAIDS & Older Adults

• Polypharmacy.

• Drug interactions.

• GI distress 4X more common.

• Hospitalization.

• Evaluate renal function.

• Edema.

• Encourage adequate hydration.

• Can NSAID dosage be lowered?

Corticosteroids (Prednisone, prednisolone, dexamethasone)

• Suppresses inflammatory components.

• Long half-life > 24 hrs.

• Taper dosing when discontinuing long-term therapy (5-10 days).

Rheumatoid Arthritis (RA)

• Autoimmune, inflammatory disease.

• Usually appears during the 3rd & 4th decade

• Incidence in younger pts: 3X greater in females

• Can be crippling.

• Symmetric joint stiffness & pain.

• Sx most intense in morning; improve as day advances.

• Joints swollen, tender, warm.

• Systemic effects:

  • Inflammation.

  • Cartilage damage.

  • Total destruction of cartilage.

• Autoimmune process: Immune system attacks synovial tissue.

RA Therapy Goals

• Relieving symptoms.

• Maintain joint function & ROM.

• Minimize systemic involvement.

• Delay disease progression.

RA Nonpharmacologic Therapy

• Physical therapy:

  • Massage, warm baths, heat application.

• Exercise: Balance of rest & exercise.

• Surgery: Total joint replacement.

• Patient education and counseling.

Disease-Modifying Antirheumatic Drugs (DMARDSs)

• Immune-mediated arthritic disease.

  • Immunosuppressive

  • Immunomodulators

  • Antimalarials.

• Most useful for rheumatoid arthritis

• Also used for Osteoarthritis, psoriatic arthritis
  Severe psoriasis, ankylosing spondylitis
  Crohn’s and ulcerative colitis

DMARDS Methotrexate (Rheumatrex)

• Most rapid-acting DMARD.

• Effects in 3 – 6 weeks.

• Give once/week, 10-20 mg/ wk.

• Oral or injection.

• Dose with 5mg folic acid to decrease toxicity

• Adverse Effects:

  • Hepatic fibrosis.

  • Bone marrow suppression.

  • GI ulceration.

  • Pneumonitis.

• Monitor LFTs, CBC, platelets, kidney function

• Contraindications Pregnancy

DMARDS Hydroxychloroquine (Plaquenil)

• Antimalarial drug.

• Usually combined with methotrexate.

• Delayed onset 3-6 months.

• Delays joint degeneration.

• Retinal damage may be irreversible.

• Pt ed: ophthalmologic exam every 6 months

Immunomodulators

• Interleukin 1 (IL-1) receptor antagonist: Anakinra: IL-1 inhibits it from binding to interleukin receptors.

  • Interleukin-1 is pro-inflammatory cytokine r/t synovial inflammation, joint destruction.

  • Subcutaneous, peak 3-7 hrs, half-life 4-6 hrs

• Tumor Necrosis Factor (TNF) Etanercept 1st TNF IL-1 receptor antagonist, TNF very expensive

• Both increase risk for severe infection

DMARDS Etancercept (Enbrel)

• Reduces RA sx and disease progression

• MOA: neutralizes TNF

• Mode of elimination unknown

• SE: injection site reaction

• AE: risk for infection

• Drug interactions: no live vaccines

• Admin:

  • Subcut injection

  • Adult 50 mg 1-2/wk

  • Cost: $16,000! per yr

GOUT

• Inflammatory disorder – severe joint pain

• Joints, tendons, other tissues (gouty arthritis)

• Disorder of uric acid metabolism and defective purine metabolism

• Hyperuricemia

  • Excessive uric acid production > 6mg/dl (female), >7 mg/dl (male)

  • Impaired renal excretion of acid

Gout - Drug Therapy

• Relieve Inflammation:

  • Colchicine

  • Indomethacin

• Reduce Hyperuricemia:

  • Allopurinol

  • Probenicid

  • Sulfinpyrazone

Colchicine

• Therapeutics – gout only

  • Treat gouty attacks

  • Reduce incidence of attacks; prevents leukocytes moving to site of inflammation

  • Prevent impending attacks

• Pharmacokinetics

  • Oral – good absorption

• Take with food to px GI irritation

• Side effects

  • GI – n/v, diarrhea, abd pain

• Adverse Effects (IV admin):

  • Bone marrow suppression, renal failure, hepatic necrosis, seizures, death

• Caution

  • Elderly, debilitated

  • Cardiac, renal, GI disease

Allopurinol

• Therapeutic use: Prevents tophi formation; improves joint function; (Reduces hyperuricemia)

• MOA: inhibits xanthine oxidase

• Pharmacokinetics

  • Oral dosing, renal excretion

  • Prolonged half life for active metabolites (up to 24 hrs)

• SE: n/v/d, abd pain; drowsiness, headache, metallic taste

• AE: hypersensitivity syndrome

  • Rash, fever, eosinophilia, liver/kidney dysfunction

• Drug interactions

  • Warfarin, mercaptopurine, theophylline, ampicillin

• Dosage/admin

  • Tabs; once a day dosing; adequate fluid intake

• Febuxostat

Uricosurics

• \uparrow rate of uric acid excretion
  Not used during acute exacerbation

• Probenecid: blocks reabsorption, promotes excretion; can take with colchicine; may take with meals

• Sulfinpyrazone: more potent than probenecid; take with food or antacid; may cause blood dyscrasias

• SE flushed skin, sore gums, HA; ­ fluid to px stones; avoid ASA (causes uric acid retention)

Analgesics

• A major reason Americans seek health care

• Social & health

  • Leading cause of disability in Americans <45y/o

• Financial impact

  • Costs $100billion/yr.

  • Causes longer hospital stays & more rehospitalizations, OP & ER visits

  • Lost workdays d/t pain >$50 million

Pain

• Considered a basic human right

  • American Bar Association

  • Pain Care Bill of Rights

• Typically undertreated

  • Purely subjective

  • Cannot be objectively measured

• Definition:

  • “Whatever the experiencing person says it is, existing whenever the person says it does.” McCaffery

  • “An unpleasant sensory and emotional experience associated with actual or potential tissue damage” IASP

• The 5th vital sign

Advances in Tx of Pain

• JCAHO adoption of pain management guidelines

  • Recognize pt’s. rights to appropriate assessment & management

  • Identify pain in pt’s. during initial assessments & prn ongoing

  • Educate health care providers in pain assessment & management & ensure competency

  • Educate pt’s. & fam. about pain management

Terms related to pain

• Pain threshold

  • Level of stimulus needed to create painful sensation

• \mu opioid receptor gene controls # of \mu -receptors present; the larger the # of receptors the higher the pain threshold

• Pain tolerance: the amount an individual can endure without altering normal function

Medications for pain

• Analgesics

  • Nonopioid

  • Opioid

• Based on severity

  • Mild to moderate use non-narcotic

  • Moderate to severe use narcotic

• NSAIDS

Pain classification by duration

• Mild Moderate Severe

• Acute: sudden, < 3 months

• Chronic: gradual onset lasting longer than 3 months

• Pain related to specific tissue injury

Dimensions of Pain - The Five Components

• A - Affective Emotions, suffering

• B - Behavioral Behavioral responses

• C - Cognitive Beliefs, attitudes, evaluations, goals

• Sensory Pain perception

• Physiologic Transmission of nociceptive stimuli

Classification of Pain - Two types of pain

• Nociceptive Ongoing activation of pain receptors on surface or deep layers of tissue (nerve endings)(injury)

  • Somatic: Well localized Aching or throbbing Bone, joint, muscle, skin, connective tissue

  • Viseral: Internal organ Intestines and bladder Tumor, obstruction, internal organs

Classifications of Pain

• Neuropathic Damage or injury to nerve fibers in the periphery or damage to CNS

• Not attributable to nociceptive activation from injury

• Sudden, stabbing, shooting, numbness; burning, tingling

• Short lived or lingering

• Diabetic neuropathy

• Responds poorly to typical pain meds

• Tricyclic Antidepressants (TCA) Amytriptyline Neurontin

Gate Control Theory Melzack & Wall (1965)

• Suggested: pain has emotional and cognitive components in addition to physical sensation

• Suggested: that gating mechanisms located along CNS can regulate or block impulses

• Pain impulses pass through a gate when open; and are blocked when closed

• Closing gate is basis for non-pharmacological interventions

Patho

• Neurohormones: endorphins suppress pain conduction

• Opioids activate same receptors

• NSAIDS control peripheral conduction by blocking cyclooxygenase, interfering with prostaglandins

• Cortisone blocks phospholipase, ¯ prostaglandins & leukotrienes

• Neuropathic pain: anticonvulsants inhibit nerve transmission

Pain assessment rating scale

• Ask patient to rate 0-10
  Use FACES for pediatric or older adults

• Consider culture

Ethical Issues

• Fear of hastening death

• Requests for assisted suicide

• Placebos sometimes still used

Acetaminophen (Tylenol)

• Analgesic & antipyretic

• No anti-inflammatory properties

• Pharmacodynamics

  • Inhibition of prostaglandin synthesis in CNS only

• Pharmacokinetics

  • Oral – well absorbed

  • Every 4 hrs***

  • Wide distribution

  • Hepatic metabolism, renal excretion

• Adverse Effects

  • Rare
    Overdose – severe liver injury
    Drug Interactions

• Alcohol

• Warfarin

• Pharmacotherapeutics

  • Pain

  • Fever

• Preferred for children if suspected of having chickenpox or flu

• Preferred for pts with PUD

Acetaminophen Toxicity

• Therapeutic serum range 10-20 mcg/mL

• S/S

  • N/V, diarrhea, sweating, abd pain

• Hepatic necrosis: hepatic failure, coma, death

• Treatment

  • Acetylcysteine (Mucomyst, Acetadote)

  • When given within 8-10 hrs of overdose, acetylcysteine is 100% effective

  • PO or IV

Nursing Implications - Acetaminophen

• High-Risk

  • Alcohol use, warfarin

• Do not exceed recommended doses

• Manage toxicity

NSAID patient education

• Take with food, milk, glass water

• Do not crush, chew

• Discard ASA preparations that smell like vinegar

• Do not consume alcohol

• Notify prescriber if gastric irritation is severe or persistent

• Teach s/s salisylism

  • Tinnitus, sweating, headache, dizziness (notify prescriber)

• Avoid ASA use in children; use acetaminophen instead (Acetaminophen: do not exceed 4 gm/day)

• Teach drug interactions