Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
53 Cards in this Set
- Front
- Back
NSAID's: Effects
|
Analgesic effect - relief of pain, minor aches
Anti-inflammatory effects - reduction of inflammation associated with various arthritic syndromes Antipyretic effect - reduction of elevated body temperature |
|
NSAID's: action locations
|
Pic
|
|
NSAID's: Analgesia, Antipyretic
|
Analgesia:
- Peripheral inhibition of prostaglandin production - Reduction of nociceptor sensitization. - Increase in pain threshold. Antipyretic: - Inhibition of prostaglandin production in hypothalamus. - Resetting of hypothalamic thermostat. |
|
NSAID's: Anti-inflammatory
|
Anti-inflammatory:
- Inhibition of prostaglandin production at site of inflammation. - Reduction of potentiative action of other mediators. - Inhibition of inflammatory mediator cascade. - Reduction of edema. - Inhibition of chemotaxis - Stabilization of lysosomal enzymes. |
|
NSAID's: Cox-1/Cox-2
|
Pic
|
|
NSAID's: Tissue damage response
|
Inflammation is a normal protective response to tissue injury.
Clinical signs of inflammation are: - erythema (redness due to vasodilation of capillaries) - edema (fluid accumulation in intercellular spaces with swelling ) - tenderness (hyperalgesia) - pain |
|
NSAID's: Inflammatory Mediators
|
Inflammatory Mediators:
- Prostaglandins - Leukotrienes - Interleukins - Tumor Necrosis Factor - Colony Stimulating Factors - Histamine, Bradykinin, Serotonin - Proteases, Collagenase, Elastase |
|
NSAID's: Inflammatory response phases
|
Inflammatory responses occur in three distinct phases:
1] Acute transient phase characterized by local vasodilation and increased capillary permeability. 2] Delayed, subacute phase most prominently characterized by infiltration of leukocytes and phagocytosis. 3] Chronic proliferative phase with tissue degeneration and fibrosis |
|
NSAID's: Injury flow chart
|
pic
|
|
Synthesis, Function, and Inhibition of Cox-1 and Cox-2
|
pic
|
|
NSAID's: Platelet synthesis
|
- Platelets have thromboxane synthetase and synthesize TXA2, a potent vasoconstrictor and inducer of platelet aggregation
- Endothelial cells synthesize PGI2 (prostacyclin), an inhibitor of platelet aggregation and a vasodilator. - Low doses of aspirin irreversibly inhibit COX and platelet aggregation for the life of the platelet (8-11 days) |
|
NSAID's: Cyclooxygenase Inhibitors
|
Aspirin
Ibuprofen (Advil) Indomethacin (Indocin) Ketorolac (Toradol) Naproxen (Naprosyn) Piroxicam (Feldene) Sulindac (Clinoril) Diclofenac (Voltaren) Diflusinal (Dolobid) |
|
NSAID's Celecoxib
|
Cyclooxygenase-2 Specific Inhibitors:
Specifically inhibits cyclooxygenase 2 enzymes. Cycoloxygenase 1 enzyme sparing effect. Reduced incidence of gastrointestinal side effects. Only one is Celecoxib |
|
Celecoxib: Contraindications
|
Do not give to Patient with History of cardiovascular problems.
|
|
NSAID's: Half-Lives
|
Ibuprofen: short half life 4 hours, prescribe at least twice daily.
Piroxicam: long 57 hour half life. Use for RA. Enhance compliance by reducing the frequency of administration. |
|
NSAID's: Clinical Indications
|
Fever
Pain Dysmenorrhea Osteoarthiritis Rheumatoid arthiritis Myocardial infarction Post-Operative Pain/Musculoskeletal Pain Dental Pain |
|
NSAID's: Aspirin
|
- Non-selectively and irreversibly inhibits both isozymes of cyclooxygenase (COX I and COX II) thereby inhibiting the synthesis of prostaglandins and thromboxanes.
- The irreversible nature of ASA's activity is related to its acetylation of the enzyme. The acetyl group from ASA covalently binds to the enzyme, permanently inhibiting its activity. - Inhibits granulocyte adherence to damaged vasculature, stabilize lysosomes - Inhibits chemotaxis of polymorphonuclear leukocytes & macrophages |
|
Aspirin: Role of Uric acid secreation
|
- At low doses , uric acid secretion is decreased, net uric acid excretion is decreased.
- At higher doses of aspirin, net uric acid excretion is increased. - This uricosuric effect of salicylates is important in patients with hyperuricemia and gout. - Salicylates can block the beneficial effects of probenecid. |
|
Aspirin: Indications
|
Low dose aspirin together with diet and exercise is indicated for the prophylaxis of:
- coronary artery disease - deep vein thrombosis - unstable angina - Myocardial infarction and stroke |
|
Aspirin: GI irritation
|
Enteric coated aspirin tablets are frequently prescribed to minimize GI irritation.
Coating dissolves once the drug reaches the small intestine. |
|
Aspirin: Contraindications
|
Reye’s syndrome is a rare but often fatal consequence aspirin use in viral infection in children.
Liver dysfunction and encephalopathy. The use of salicylates in children is contraindicated. |
|
Acetaminophen (Paracetamol):
|
- Indicated for temporary relief of mild to moderate pain and fever reduction
- No anti inflammatory action - No antiplatelet activity - No significant gastrointestinal side effects. Effective alternative when aspirin is contraindicated (drug of choice for antipyresis in children) |
|
Ibuprofen (Advil)
Naproxen (Naprosyn) |
- Highly effective anti-inflammatory and analgesic agents.
- 80% absorbed from GI tract - Symptomatic treatment of gout, rheumatoid arthritis, osteoarthritis. |
|
Diflusinal (Dolobid):
|
- Effective analgesic for osteoarthritis and musculoskeletal sprains.
- Relief of pain occurs through both peripheral and central mechanism - Low doses irreversibly inhibit thromboxane production in platelets - Has a half life of 8-12h and approximately 4 times potency of aspirin. |
|
Indomethacin (Indocid):
|
- Potent NSAID - rapidly and completely absorbed from GI tract
- Highly bound to plasma proteins - Prominent anti-inflammatory, antipyretic and analgesic activity - Reduces polymorphonuclear leukocyte motility - Reduces development of cellular exudates and reduces vascular permeability in injured tissue. |
|
Indomethacin: Indications
|
- Highly indicated in treatment of rheumatoid arthritis, acute gouty arthritis, osteoarthritis.
- Indicated for closure of patent ductus arteriosus. |
|
Sulindac (Clinoril):
|
- 90% absorbed after oral administration
- Prodrug - transformed to sulfide metabolite in liver - Highly potent cyclooxygenase inhibitor - Half-life: Sulindac: 7h - Sulfide metabolite: 18h |
|
Sulindac (Clinoril):
Indications |
- Indicated for acute and long-term treatment of osteoarthritis, rheumatoid arthritis, bursitis and acute gouty arthritis.
- Active metabolite and long half-life allows for once or twice daily dosing. |
|
Piroxicam (Feldene)
Meloxicam (Mobic) |
- Long-term treatment of rheumatoid arthritis, osteoarthritis, acute gout.
- Long half-life permits once daily dosing. - Good for Gout |
|
Ketorolac (Toradol)
|
- Potent analgesic action.
- Moderate anti-inflammatory action. - Alternative to opioids for short-term treatment of moderate pain. - Parenteral and oral formulations. |
|
Dicolfenac (Voltaren):
|
- High selectivity for COX-2.
- Long-term treatment of osteoarthritis, ankylosing spondylitis (accumulates in synovial fluid). - Short term treatment of acute musculoskeletal and postoperative pain. - Intermediate-release, delayed release and extended-release forms. |
|
Celecoxib (Celebrex):
|
- Selective for COX-2.
- Less incidence of GI ulcers, less effect on platelets and bleeding time. - Approved for dysmenorrhea, osteoarthritis, and rheumatoid arthritis, acute post-operative pain |
|
A pt w Hx of peptic ulcer disease developes RA and requires an NSAID for treatment. Which do you use?
|
Celecoxib: will not damage GI.
|
|
Celecoxib (Celebrex):
|
- Does not have any effect on platelet aggregation or bleeding time.
- Very well absorbed and undergoes extensive hepatic metabolism. - Long half-life of 11 hours allows for once daily dosing. |
|
Analgesic Strength Profile:
|
- Ketorolac > Naproxen > Ibuprofen > Aspirin
- Ketorolac indicated for postoperative analgesia (PO/IM) - NSAID’s do not reduce progression of joint disease in rheumatoid arthritis. |
|
NSAID's: Shared Toxic Side Effects -
Gastrointestinal |
- Dyspepsia, abdominal pain. Diarrhea.
- Induction of gastric and intestinal ulcers. - Exacerbation of peptic ulcers. - High concentrations may damage gastric mucosa. - Inhibition of prostaglandin synthesis in the gastric mucosa leads to increased acid secretion. |
|
To prevent GI injury:
|
- Use COX-2 specific inhibitor.
- Prescribe lowest effective dose of NSAID - Administer co-therapy -- Misoprostol -- High-dose H2-receptor antagonist -- Proton pump inhibitor - Avoid concomitant anticoagulant or corticosteroid use |
|
NSAID's: Shared Toxic Side Effects: Cardio, Renal
|
Cardiovascular:
COX-2 selective inhibitors may increase risk of thrombosis. Increased risk of stroke and myocardial infarction. Acute Renal Failure: Patients with compromised renal function are susceptible to NSAID induced nephrotoxicity. |
|
NSAID's: Shared Toxic Side Effects:
Hypersenstivity, Pregnancy |
Hypersenstivity:
- Vasomotor rhinitis, angioedema, urticaria. - Bronchoconstriction, flushing. - Hypotension. Pregnancy: - NSAID’s contraindicated in third-trimester due to risk of post-partum hemorrhage and delayed labor. |
|
NSAID’s:
Drug Interactions
|
- Many NSAID’s are highly bound to plasma protein.
- Displacement of previously bound drugs increases toxicity risk - anticoagulants, phenytoin, sulfonamide, sulfonylureas |
|
Hyperuricemia & Gout
|
- Uric acid is the end-product of purine metabolism.
- Excreted by kidney through filtration, secretion. - Hyperuricemia results if the rate of production of uric acid exceeds the rate of elimination (underexcretion) - At high enough plasma concentrations, uric acid becomes insoluble, crystallizes. |
|
Hyperuricemia & Gout:
|
- Crystals of sodium urate deposit in joints
- Granulocytes phagocytize urate crystals in the joints and an inflammatory response ensues - Local production of lactate lowers the local pH causes further precipitation of crystals - Further release of inflammatory mediators and lysosomal enzymes. - Synovial inflammation |
|
Rate limiting step of Uric acid:
|
pic
|
|
Purines --> uric acid
|
pic
|
|
Monosodium crystals:
|
causes excruciating pain.
|
|
Gout Management:
|
Treat Acute Pain & Inflammation
Reduce Frequency of Attacks Reduce Consequences of Hyperuricemia: - Acute Gout - Tophi - Renal Lithiasis - Acute Tubular Blockade |
|
NSAID's: First thing you do for Gout
|
- Acute gout attacks are extremely painful with extensive inflammation and heat production at site.
- Indomethacin or Ibuprofen is the initial drug of choice in acute attacks - Naproxen or Diclofenac may also be considered. |
|
Colchicine:
|
- Binds to tubulin in mitotic spindles and other microtubular structures of cells.
- Arrests cell division, cell mobility, and the release of chemotactic factors. - Inhibits migration of granulocytes into inflamed area and decreases their phagocytic activity - Inhibition of mast cell degranulation. 1mg first hour, and .5mg every hour until symptoms disappear or until diarhea. Dr. Krisha says to give one dose of colchicine only. |
|
Colchicine: Effects
|
Provides dramatic relief from acute attacks of gout
Given within first few hours of an acute attack, oral doses Pain, swelling, and redness abate within 12 hours Diarrhea, nausea, vomiting limit and high toxicity (bone marrow suppression) limits duration of therapy. |
|
Allopurinol (Zyloprim)
|
- Used for the treatment of hyperuricemia and chronic gout
- Competitively inhibits xanthine oxidase, the enzyme that catalyzes the final steps in uric acid formation. - Reduction in plasma uric acid levels. - Well tolerated - Avoid during acute attack of gouty arthritis. |
|
Allopurinol (Zyloprim): MOA
|
Metabolized in liver to active metabolite: oxypurinol.
↓ Slow excretion in urine (15-30h) - Cautious use in hepatic and renal impairment (dosage adjustment required) |
|
Probenicid:
|
- Blocks proximal tubular reabsorption of uric acid and is used to lower serum levels in chronic gout
- Oral doses twice daily combined with liberal fluid intake until uric acid levels are controlled |
|
Why is allopurinol effective in gout?
1. It increase uric acid synthesis 2. It increases uric acid degradation 3. It decreases uric acid production 4. increasesa renal excreation of uric acid 5. reducesd inflammation |
3. It decreases uric acid production
|