Chapter 25 ANTIINFLAMMATORY DRUGS

Antiinflammatory Drugs Pathophysiology Inflammation Reaction to tissue injury Caused by release of chemical mediators Leads to a vascular response Fluid and WBCs migrate to injured site Chemical mediators Histamines Kinins Prostaglandins

Antiinflammatory Drugs (cont’d) Pathophysiology Chemical mediators Histamines First mediator in inflammatory process Cause dilation of arterioles Increase capillary permeability Kinins (Bradykinin) Increase capillary permeability Increase pain Prostaglandins Increase capillary permeability Increase vasodilation Increase pain and fever

Antiinflammatory Drugs (cont’d) Pathophysiology Cardinal signs of inflammation Redness Swelling Heat Pain Loss of function

Antiinflammatory Drugs (cont’d) Pathophysiology Inflammation Cyclo-oxygenase (COX) enzyme Converts arachidonic acid into prostaglandins Has two enzyme forms: oCOX-1: protects stomach lining and regulates blood platelets oCOX-2: triggers inflammation and pain

Antiinflammatory Drugs (cont’d) Antiinflammatory drug groups Nonsteroidal antiinflammatory drugs (NSAIDs) Corticosteroids Disease-modifying antirheumatic drugs Antigout drugs

Antiinflammatory Drugs (cont’d) NSAIDs Inhibit biosynthesis of prostaglandins Analgesic effect Antipyretic effect Inhibit platelet aggregation Mimic effects of corticosteroids

NSAIDs Action Inhibit COX enzyme Inhibit prostaglandin synthesis Uses Reduce inflammation and pain Not recommended for fever or headaches Except aspirin, ibuprofen

NSAIDs (cont’d) First-generation NSAIDs Salicylates (aspirin) Parachlorobenzoic acid Pyrazolone derivatives Propionic acid derivatives Fenamates Oxicams Phenylacetic acid derivatives Second-generation NSAIDs COX-2 inhibitors

Salicylates Aspirin (acetylsalicylic acid) (ASA) Action Antiinflammatory, antiplatelet, antipyretic effects Therapeutic serum salicylate level 10 to 30 mg/dl Toxic serum salicylate level Greater than 30 mg/dL

Salicylates (cont’d) Drug-lab-food interactions Drugs Increased bleeding with anticoagulants Hypoglycemia with oral antidiabetics Increased gastric ulcer risk with glucocorticoids Lab Increase PT, bleeding time, INR, uric acid Decrease potassium, cholesterol, T 3 and T 4 levels Foods containing salicylates Prunes, raisins, licorice, certain spices

Salicylates (cont’d) Aspirin Caution Do not take with other NSAIDs. Avoid during third trimester of pregnancy. Do not give to children with flu or virus symptoms (Reye’s sydrome). Side effects/adverse reactions Tinnitus, hearing loss Dizziness, confusion, drowsiness GI distress, peptic ulcer Thrombocytopenia, leukopenia, agranulocytosis Hepatotoxicity

Salicylates (cont’d) Hypersensitivity Tinnitus, dizziness, bronchospasm Salicylism (mild) Tinnitus, dizziness, headache, confusion, sweating, drowsiness, thirst, nausea, vomiting, diarrhea Severe salicylate poisoning Convulsions, cardiovascular collapse, coma

Propionic Acid Derivatives Ibuprofen (Motrin, Advil) Nonselective COX inhibitors Drug interactions Increased bleeding with warfarin, increased effects with phenytoin, sulfonamides, warfarin Decreased effect with aspirin Side effects Gastric distress (to be taken with food) Tinnitus, dizziness, confusion, edema Blood dyscrasias, dysrhythmias, nephrotoxicity Other propionic acid drugs Naproxen (Naprosyn) Oxaprozin (Daypro)

COX-2 Inhibitors Action Selectively inhibits COX-2 enzyme without inhibition of COX-1 Use Decrease inflammation and pain Drug agents Celecoxib Similar agents Nabumetone (Relafen), meloxicam (Mobic) Some COX-1 inhibition

COX-2 Inhibitors (cont’d) Caution Avoid during third trimester of pregnancy. Side effects Headache, dizziness, sinusitis GI distress Peripheral edema NSAIDs in older adults Greater incidence of GI distress, ulceration Reduced dose decreases risk of side effects

Disease-Modifying Antirheumatic Drugs Gold drug therapy (chrysotherapy) Immunosuppressive agents Immunomodulators Antimalarials

Disease-Modifying Antirheumatic Drugs (cont’d) Gold drug therapy Auranofin (Ridaura) Action Decreases leukocytes migration. Suppresses prostaglandin synthesis. Stops progression of joint degeneration. Use Rheumatoid arthritis

Disease-Modifying Antirheumatic Drugs (cont’d) Gold drug therapy Side effects/adverse reactions Photosensitivity, corneal gold deposits Stomatitis, metallic taste Bradycardia, profound hypotension GI distress, severe rash Hematuria, proteinuria Nephrotoxicity, agranulocytosis, thrombocytopenia Contraindications Severe renal or hepatic disease Pregnancy, blood dyscrasias, colitis Systemic lupus erythematosus

Immunomodulators Tumor necrosis factor (TNF) blockers Entanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Anakinra (Kineret) Abatacept (Orencia) Action Neutralize TNF Disrupt inflammatory process Delay disease progression Used for rheumatoid arthritis

Immunomodulators (cont’d) Infliximab (Remicade) Side effects/adverse reactions Headache, dizziness, depression Chills, hot flashes Hypotension, hypertension GI distress Urinary frequency Altered liver enzymes Severe infections Contraindications Renal or hepatic disease Immunosuppression, infection

Antigout Drugs Gout pathophysiology Inflammatory disease of joints, tendons Usually occurs in great toe Defect in purine metabolism leads to uric acid accumulation Purine-containing foods: salmon, liver, sardines Antigout drugs Colchicine Uric acid inhibitors Uricosurics

Antigout Drugs (cont’d) Colchicine Inhibit migration of leukocytes to inflamed site Side effects GI distress Taken with food to avoid GI distress Contraindications Severe renal, cardiac, or GI problem

Antigout Drugs (cont’d) Uric acid inhibitors Allopurinol (Zyloprim) Action Decreases production of uric acid Prophylactic to prevent gout attacks Nursing Interventions Monitor CBC, liver enzymes, renal function. Tell client to get yearly eye examinations for visual changes. Advise client to avoid alcohol, caffeine, and thiazide diuretics that increase uric acid level. Advise client to increase fluid intake to increase uric acid excretion.

Antigout Drugs (cont’d) Uricosurics Probenecid (Benemid) Action Increases uric acid excretion by blocking reabsorption of uric acid Side effects Gastric irritation; client should take with food. Nursing Interventions It is not to be given with other highly protein-bound drugs. Client should increase fluid intake to increase uric acid excretion.

Case Study A client with gout is prescribed the antiinflammatory drug colchicine. Critical Thinking 1.Compare the action of colchicine with that of uric acid inhibitors and uricosurics. 2.In what case would colchicine be contraindicated?

Practice Question #1 Which teaching does the nurse realize would have the highest priority for the client with gout who is taking colchicine? A.Increase vitamin C. B.Avoid alcohol and caffeine. C.Increase foods high in purine. D.Take colchicine 2 hours before meals.

Practice Question #1 (cont’d) Answer: B Rationale: Alcohol and caffeine are to be avoided because they may increase uric acid levels. Vitamin C should not be taken in large doses because it may promote kidney stone formation. Purine foods increase uric acid levels and should be avoided. Antigout medications, especially colchicine, should be taken with food or at mealtime.

Practice Question #2 A client has been advised to take ibuprofen (Motrin). Which topic should the nurse teach the client about Motrin? (Select all that apply.) A. Tell client to avoid taking aspirin with Motrin. B. Advise client to take with food to reduce GI upset. C. Monitor for bleeding gums, nosebleeds, black tarry stools. D. Encourage client to take herbs, such as ginkgo and garlic, with Motrin. E. Advise female clients to take NSAIDs 2 days before menstruation to decrease discomfort.

Practice Question #2 (cont’d) Answer: A, B, C Rationale: One should avoid aspirin with NSAIDs. Food may be taken with NSAIDs to reduce GI upset. Clients should be taught to monitor for bruising and bleeding. Many herbs, such as ginkgo, garlic, and ginger should be avoided because bleeding may increase. Female clients should avoid NSAIDs for 1 to 2 days before menses to prevent excessive bleeding.