chapter 49 anti inflammatory and antigout drugs Flashcards
inflammation
Localized protective response stimulated by injury to tissues, which serves to destroy, dilute, or wall off (sequester) both the injurious agent and the injured tissue
Pain, fever, loss of function, redness, and swelling
Endogenous compounds, including proteins of the complement system, histamine, serotonin, bradykinin, leukotrienes, and prostaglandins
NSAIDs uses
Uses of NSAIDs
Relief of mild to moderate headaches
Relief of myalgia
Relief of neuralgia
Relief of arthralgia
Relief of postoperative pain
Relief of pain associated with arthritic disorders such as rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis, and osteoarthritis
Treatment of gout and hyperuricemia
properties of Nsaids
Properties all NSAIDs share:
Antipyretic properties
Analgesic properties
Anti-inflammatory properties
aspirin
Shown to reduce cardiac death after myocardial infarction (MI)
Should be administered at the first sign of MI
If aspirin is not given before the patient arrives at the emergency department, it is one of the first drugs given if there are no contraindications.
NSAIDs mechanism of action
Inhibition of the leukotriene pathway, the prostaglandin pathway, or both
Blocking the chemical activity of the enzyme COX
COX-1 has a role in maintaining the gastrointestinal (GI) mucosa.
COX-2 promotes synthesis of prostaglandins involved in the inflammatory process.
aspirin
Irreversible inhibitor of COX-1 receptors within the platelets themselves
Reduced formation of thromboxane A2, a substance that normally promotes platelet aggregation (also known as antiplatelet activity)
Other NSAIDs lack these antiplatelet effects.
NSAIDs: Contraindications
Known drug allergy
Conditions that place the patient at risk for bleeding
Rhinitis
Vitamin K deficiency
Peptic ulcer disease
NSAIDs: Adverse Effects
Heartburn to severe GI bleeding
Acute kidney injury
Noncardiogenic pulmonary edema
Altered hemostasis
Hepatotoxicity
Skin eruption, sensitivity reaction
Tinnitus, hearing loss
misoprostol
Many of the adverse effects of NSAIDs are secondary to their inactivation of protective prostaglandins that help maintain the normal integrity of the stomach lining.
Prevents GI bleed
A synthetic prostaglandin E1 analogue: inhibits gastric acid secretion and has a cytoprotective component
Mechanism of action: unclear
NSAIDs and Kidney Function
Kidney function depends partly on prostaglandins.
Disruption of prostaglandin function by NSAIDs is sometimes strong enough to precipitate acute or chronic kidney injury or failure.
Use of NSAIDs can compromise existing kidney function.
Kidney toxicity can occur in patients with dehydration, heart failure, or liver dysfunction, or with the use of diuretics or angiotensin-converting enzyme inhibitors.
NSAIDs: Health Canada Warning
All NSAIDs (except aspirin) share a Health Canada warning regarding an increased risk of adverse cardiovascular thrombotic events, including fatal MI and stroke.
NSAIDs cause an increased risk of serious GI adverse events
Older adults are at greater risk.
Salicylates
acetylsalicylic acid (aspirin) the most common
Oral (tablets, capsules), topical cream (Aspercreme®), oral liquids, rectal suppositories
aspirin–antacid combinations (Alka-Seltzer®)
Enteric-coated aspirin (Praxis ASA EC®)
acetylsalicylic acid (aspirin)
Inhibits platelet aggregation
Antithrombotic effect: used in the treatment of MI and other thromboembolic disorders
Reye’s syndrome
Patients with systemic lupus erythematosus may benefit from aspirin therapy because of its antirheumatic effects.
aspirin: Forms
Daily tablet (81 mg or 325 mg): prophylactic therapy for adults who have strong risk factors for developing coronary artery disease or cardiovascular accident
Effective after MI
The 81- and 325-mg strengths appear to be equally beneficial for the prevention of thrombotic events.
aspirin: Uses
Headache, neuralgia, myalgia, and arthralgia
Pain syndromes resulting from inflammation: arthritis, pleurisy, and pericarditis
Systemic lupus erythematosus: antirheumatic effects
Antipyretic action
aspirin: Reye’s Syndrome
Acute and potentially life-threatening condition involving progressive neurological deficits that can lead to coma and may also involve liver damage
Triggered by viral illnesses such as influenza, as well as by salicylate therapy itself in the presence of a viral illness.
Survivors of this condition may or may not have permanent neurological damage.
Salicylates
Salicylate intoxication (when chronic, known as salicylism)
Increased heart rate
Tinnitus, hearing loss, dimness of vision, headache, dizziness, mental confusion, drowsiness
Nausea, vomiting, diarrhea
Sweating, thirst, hyperventilation, hypoglycemia or hyperglycemia
Acetic Acid Derivatives
indomethacin
Analgesic, anti-inflammatory, antirheumatic, and antipyretic properties
Uses: therapy for rheumatoid arthritis (RA), osteoarthritis (OA), acute bursitis or tendonitis, ankylosing spondylitis, acute gouty arthritis
Oral and rectal routes
ketorolac tromethamine (Toradol)
Some anti-inflammatory activity
Used primarily for its powerful analgesic effects, which are comparable to those of narcotic drugs such as morphine sulphate
Indication: short-term use (up to 5 to 7 days) to manage moderate to severe acute pain
Adverse effects: kidney impairment, edema, GI pain, dyspepsia, and nausea
Propionic Acid Derivatives
ibuprofen (Motrin, Advil)
Most commonly used NSAID
Uses: analgesic effects in the management of RA, OA, primary dysmenorrhea, dental pain, musculoskeletal disorders; antipyretic actions
naproxen
Second most commonly used NSAID
Somewhat better adverse effect profile than ibuprofen
Fewer drug interactions with angiotensin-converting enzyme inhibitors given for hypertension
Cyclo-oxygenase-2 (COX-2) Inhibitor
celecoxib (Celebrex®)
First and only remaining COX-2 inhibitor
Indicated for OA, RA, acute pain symptoms, ankylosing spondylitis, and primary dysmenorrhea
Adverse effects include headache, sinus irritation, diarrhea, fatigue, dizziness, lower-extremity edema, and hypertension
Little effect on platelet function
Not to be used in patients with known sulpha allergy
Enolic Acid Derivatives
piroxicam
meloxicam
nabumetone
Used to treat mild to moderate OA, RA, and gouty arthritis
nabumetone is better tolerated in terms of GI adverse events than are some other NSAIDs.
NSAIDs: Adverse Effects
GI
Dyspepsia, heartburn, epigastric distress, nausea, vomiting, anorexia, abdominal pain
GI bleeding*
Mucosal lesions* (erosions or ulcerations)
Renal
Reductions in creatinine clearance
Acute tubular necrosis with acute kidney injury
Cardiovascular
Noncardiogenic pulmonary edema
*Misoprostol can be used to reduce these dangerous effects.
Gout
A condition that results from inappropriate uric acid metabolism
Underexcretion of uric acid
Overproduction of uric acid
Uric acid crystals are deposited in tissues and joints, resulting in pain
Hyperuricemia
Antigout Drugs
allopurinol (Zyloprim®)
febuxostat (Uloric®)
colchicine
probenecid (Benuryl®)
sulfinpyrazone
Antigout Drugs: Indications
allopurinol (Zyloprim)
Used to prevent uric acid production and to prevent acute tumour lysis syndrome
Also used for exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis
probenecid (Benuryl)
Inhibits the reabsorption of uric acid in the kidneys and thus increases the excretion of uric acid
colchicine
Oldest available therapy
Reduces the inflammatory response to the deposits of urate crystals in joint tissue
Powerful inhibitor of cell mitosis, and can cause short-term leukopenia
Prophylaxis of acute attacks in dosages of 0.6 mg once or twice a day
Herbal Products: Glucosamine and Chondroitin
Used to treat the pain of OA
Glucosamine adverse effects:
GI discomfort
Drowsiness, headache, skin reactions
Chondroitin adverse effect:
GI discomfort (normally well tolerated)
Drug interactions
Enhance the effects of warfarin
Glucosamine may increase insulin resistance
