Ch 33 Drugs for inflammation

Inflammation

• Natural, nonspecific defense mechanism

• Occurs in response to injury, antigen, toxic chemicals, extreme heat, invading microorganisms, or death of cells

• contain the injury or destroy the antigen by neutralizing the foreign agent & removing cellular debris & dead cells,

  • repair of the injured area can proceed at a faster pace

• S&S

  • swelling, pain, warmth, & redness of the affected area

• Acute: immediate onset, 8-10 days to begin

• Chronic: slower onset and lacks the distinct stages characteristic of acute

  • i.e. systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)

Chemical mediators in inflammation

• Alert surrounding tissue of injury:

  • Histamine

  • Leukotrienes

  • Bradykinin

  • Complement

  • Prostaglandins

Acute inflammatory

• Occurs after cellular injury causes release of chemical mediators

• Five basic steps

  1. Vasodilation (redness, heat)

  2. Vascular permeability (edema)

  3. Cellular infiltration (pus)

  4. Thrombosis (clots)

  5. Stimulation of nerve endings (pain)

Histamine

• Key chemical mediator in inflammation

• Stored & released by mast cells

• Initiates inflammatory response, responsible for symptoms of anaphylaxis

• Directly stimulates pain receptors

• Causes vasodilation, smooth-muscle contraction, tissue swelling, & itching

  • Capillaries become leaky = tissue swelling

• can produce its effects by interacting with two different receptors:

  • H₁ & H₂

H₁ receptors

• Found in vascular smooth muscle, in bronchi, and on sensory nerves

• Stimulation results in itching, pain, edema, vasodilation, bronchoconstriction

• Characteristic of inflammation and allergy

H₂ receptors

• Located in stomach

• Stimulation results in secretion of hydrochloric acid

General Strategies for Treating Inflammation

• Main goal: Prevent or decrease intensity of inflammation & reduce fever if present

  • Cause should be identified & treated

  • Nonpharmalogic treatment should be used whenever applicable

  • Topical anti-inflammatory should be used when applicable as few AE

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Primary drugs for treatment of mild to moderate inflammation & fever

• act by inhibiting the synthesis of prostaglandins (that promote inflammation)

  • blocking inflammation by inhibiting cyclooxygenase (COX), (key enzyme in the biosynthesis of prostaglandins)

• All have about same efficacy & All are analgesics and antipyretics

• Side effects vary

  • stomach pain, heartburn

• i.e. Salicylates, Aspirin, Ibuprofen and ibuprofen-like NSAIDs, COX-2 Inhibitors

  • Acetaminophen has no anti-inflammatory action and is not an NSAID

Salicylates

• Treats inflammation by inhibiting both COX-1 and COX-2

• Readily available, inexpensive, effective

• Large doses needed to relieve severe inflammation

• i.e. Aspirin 

Aspirin

• potent inhibitor of thromboxane, inhibits both COX-1 & COX-2

• readily available, inexpensive, & effective, 

• used for treating mild pain & inflammation

• Protective effect on the cardiovascular system

• Large doses may result in AE

  • Epigastric pain, heartburn, ulcer bleeding, GI bleeding, salicylism

    • (Tinnitus, dizziness, headache, excessive perspiration)

Ibuprofen and ibuprofen-like NSAIDs

• Alternatives to aspirin

• Effects through inhibition of both COX-1 and COX-2

• Low incidence of adverse effects when used intermittently

• Common effects:

  • Frequent: Nausea, vomiting

  • Potential: gastric ulceration, bleeding, nephrotoxicity, hypertension

Selective COX-2 Inhibitors

• produces analgesic, anti-inflammatory, & antipyretic effects w/o causing some serious AE of the older NSAIDs by targeting only COX-2

  • Don’t inhibit COX-1 (no affect to blood coagulation & digestive system)

• Was preferred treatment for moderate to severe inflammation until some drugs doubled the risk fo heart attack

  • Increased risk of cardiovascular events

  • Celecoxib (Celebrex) only remaining COX-2 inhibitor

Corticosteroids

• Effective in treating severe inflammation

• Naturally released from adrenal cortex

• Suppress histamine and prostaglandins

• Can inhibit immune system to reduce inflammation

• able to enter breastmilk

• Used for short-term treatment of acute inflammation due to long term AE

• Serious AE:

  •  mood swings, weight gain, acne, facial flushing, nausea, insomnia, sodium & fluid retention, impaired wound healing, menstrual abnormalities, hyperglycemia, increased appetite

  • Peptic ulcer, hypocalcemia, osteoporosis w/possible fractures, loss of muscle mas, decreased growth in children, masking infections, immunosuppression, fetal harm

• Can mask infections:

  • Create potential for existing infection to grow rapidly and undetected

  • Contraindicated in active infections

• i.e. prednisone

Antipyretics

• drugs that treat fever

• Goal: lower body temperature while treating the underlying cause of the fever (usually infection)

• i.e. Aspirin, ibuprofen, acetaminophen

Drugs that are known to induce fever

• Anti-infectives: may be seen as foreign body & induce fever

• Selective serotonin reuptake inhibitors (SSRIs): can result in high fever w/ serotonin syndrome

• Conventional antipsychotic drugs: may produce elevated temp. w/ neuroleptic malignant syndrome

• Volatile anesthetics and depolarizing neuromuscular blockers: can cause life-threatning malignant hyperthermia

• Immunomodulators: may cause flu-like syndrome

• Cytotoxic drugs: dampen immune response & result in fever

• Drugs that cause neutropenia

Recognize and Analyze Cues

• Gather a comprehensive health & drug history, including allergies and current medications.

• Check for possible drug interactions & obtain baseline vital signs and lab results.

• Identify potential health issues based on the assessment data, such as risk for adverse drug reactions or ineffective management of symptoms.

Prioritize and Generate Solutions

• Set goals and outcomes for the patient's treatment.

• Educate patients on proper drug administration, emphasizing the importance of using appropriate measuring devices and avoiding aspirin in children under 19.

Take action

• Administer medications and provide patient education during care.

• Monitor for adverse effects, especially with corticosteroids and NSAIDs, and ensure medications are not stopped abruptly.

Evaluate Outcomes

• Continuously monitor the patient's response to treatment, adjusting the care plan as needed to achieve desired health outcomes.

Fever

• natural defense mechanism for neutralizing foreign organisms, usually caused by infections

  • in young children fever can stimulate febrile seizures

  • In adults fever can break down body tissues, reduce mental acuity, & lead to delirium or coma

  • Some fevers may be beneficial in killing bacteria hence must decide if to aggressively treat or allow course

COX-1

• Present in all tissues

• Sevres protective functions

  • Results undesirable effects:

    • Bleeding, gastric upset, reduced kidney function

COX-2

• Formed only after tissue injury 

• Serves to promote inflammation

Prostaglandins

• Lipids stored & released by mast cells

• Increase capillary permeability

• Attracts WBC to site, cause pain, & induce fever

Complement

• 20 series protein that combines in cascade fashion to neutralize or destroy antigens

Bradykinin

• inactive form protein present in plasma & mast cells

• Vasodilator that causes pain

• Effects similar to histamine

Leukotrienes

• Lipids stored & released by mast cells

• Effects similar to histamine

• Contribute to symptoms of asthma & allergies