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55 Cards in this Set
- Front
- Back
Which enzyme converts membrane lipids (eg, phosphatidylinositol) to arachidonic acid? What drugs inhibit this?
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Phospholipase A2
- Inhibited by corticosteroids |
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What enzyme converts arachidonic acid to leukotrienes? Which drug inhibits this?
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Lipoxygenase
- Inhibited by Zileuton ("E" in Zileuton for enzyme") |
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Which leukotriene(s) is/are a neutrophil chemotactic agent?
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LTB4: neutrophils arrive "B4" others
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Which leukotriene(s) function in bronchoconstriction, vasoconstriction, contraction of smooth muscle, and ↑ vascular permeability? Which drugs inhibit this?
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LTC4, LTD4, LTE4
- Inhibited by Zafirlukast and Montelukast |
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Which enzyme converts arachidonic acid to prostaglandins? Which drugs inhibit this?
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Cyclooxgenase (COX-1 and COX-2)
- Inhibited by NSAIDs, aspirin, acetaminophen, and COX-2 inhibitors - Inhibited by corticosteroids by inhibiting protein synthesis |
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Which prostaglandin inhibits platelet aggregation, promotes vasodilation (↓ vascular tone), ↓ bronchial tone, and ↓ uterine tone?
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PGI2 = Platelet Gathering Inhibitor
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Which prostaglandin ↑ uterine tone and ↓ bronchial tone?
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PGE2 and PGF2α
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Which arachidonic acid product ↑ platelet aggregation, ↑ vascular tone, and ↑ bronchial tone?
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TXA2 (Thromboxane)
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What is the function of LTB4?
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Neutrophil chemotaxis (Neutrophils arrive B4 others)
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What is the function of LTC4, LTD4, and LTE4?
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- ↑ Bronchial tone (bronchoconstriction)
- Vasoconstriction - Contraction of smooth muscle - ↑ Vascular permeability |
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What is the function of PGI2 (Prostacyclin)?
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- ↓ Platelet aggregation (PGI = platelet gathering inhibitor)
- ↓ Vascular tone - ↓ Bronchial tone - ↓ Uterine tone |
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What is the function of PGE2 and PGF2α (prostaglandins)?
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- ↑ Uterine tone
- ↓ Bronchial tone |
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What is the function of Thromboxane (TXA2)?
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- ↑ Platelet aggregation
- ↑ Vascular tone - ↑ Bronchial tone |
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What is the mechanism of Aspirin?
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- Irreversible inhibition of cyclooxygenase (COX-1 and COX-2) by covalent acetylation
- Decreases synthesis of Thromboxane A2 (TXA2) and Prostaglandins |
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What is the effect of aspirin on bleeding?
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- ↑ Bleeding time until new platelets are produced (~7 days)
- No effect on PT or PTT |
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What are the clinical uses of Aspirin?
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- Low dose (<300 mg/day): ↓ platelet aggregation
- Intermediate dose (300-2400 mg/day): antipyretic and analgesic - High dose (2400-4000 mg/day): anti-inflammatory |
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What are the toxic side effects of Aspirin?
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- Gastric ulceration
- Tinnitus (CN VIII) - Chronic use can lead to: acute renal failure, interstitial nephritis, upper GI bleeding - Reye syndrome in children treated for viral infection - Stimulates respiratory centers: hyperventilation and respiratory alkalosis |
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What causes Reye Syndrome?
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Occurs in children treated with aspirin for a viral infection
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What are the types of NSAIDs?
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- Ibuprofen
- Naproxen - Indomethacin - Ketorolac - Diclofenac |
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What is the mechanism of NSAIDs?
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- Reversibly inhibits cyclooxygenase (COX-1 and COX-2)
- Blocks prostaglandin synthesis |
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How are NSAIDs used clinically?
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- Anti-pyretic
- Analgesic - Anti-inflammatory - Indomethacin is used to close a PDA |
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What drug can be used to close a patent ductus arteriosus? Mechanism?
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Indomethacin (NSAID) - reversibly inhibits cyclooxygenase, blocking prostaglandin synthesis
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What are the toxic side effects of NSAIDs?
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- Interstitial nephritis
- Gastric ulcer (PGs protect gastric mucosa) - Renal ischemia (PGs vasodilate afferent arteriole) |
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How do NSAIDs affect the kidney?
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- Can cause interstitial nephritis
- Can cause renal ischemia (PGs vasodilate afferent arteriole) |
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What drug is a specific COX-2 inhibitor?
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Celecoxib
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What is the mechanism of Celecoxib?
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Reversibly inhibits COX-2, which is found in inflammatory cells and vascular endothelium and mediates pain
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How is Celecoxib hypothetically better than NSAIDs?
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- Spares COX-1, which helps maintain gastric mucosa
- Should not have the corrosive effects of other NSAIDs on GI lining - Spares platelet function as TXA2 production is dependent on COX-1 |
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What are the uses of Celecoxib?
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- Rheumatoid arthritis
- Osteoarthritis - Patients with gastritis or ulcers |
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What are the toxic side effects of Celecoxib?
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- Increased risk of thrombosis
- Sulfa allergy |
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What is the mechanism of Acetaminophen?
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- Reversibly inhibits cyclooxygenase, mostly in CNS
- Inactivated peripherally |
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What are the clinical uses of Acetaminophen?
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- Anti-pyretic
- Analgesic - NOT anti-inflammatory - Used instead of aspirin to avoid Reye syndrome in children with a viral infection |
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How do NSAIDs compare to Acetaminophen?
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Both have anti-pyretic and analgesic action, but only NSAIDs are anti-inflammatory
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What are the toxic side effects of Acetaminophen?
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- Overdose produces hepatic necrosis
- Acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver |
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What is the antidote for an Acetaminophen overdose? Mechanism?
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N-acetylcysteine - regenerates glutathione
Remember: Acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver |
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What are the names of bisphosphonate drugs?
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- Alendronate
- Other -dronates |
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What is the mechanism of Bisphosphonates (Alendronate)?
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Pyrophosphate analogs
- Binds hydroxyapatite in bone - Inhibits osteoclast activity |
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What are the clinical uses of Bisphosphonates (Alendronate)?
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- Osteoporosis
- Hypercalcemia - Paget disease of the bone |
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What are the toxic side effects of Bisphosphonates (Alendronate)?
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- Corrosive esophagitis (patients are advised to take with water and remain upright for 30 minutes)
- Osteonecrosis of the jaw |
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What drugs can be used to prevent gout flares (chronic)?
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- Allopurinol
- Febuxostat - Probenecid |
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What drugs can be used to treat gout flares (acute)?
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- NSAIDs
- Glucocorticoids - Colchicine |
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What is the mechanism of Allopurinol?
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Inhibits Xanthine Oxidase
- ↓ Conversion of xanthine to uric acid |
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What are the uses of Allopurinol?
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- Chronic gout drug (preventive)
- Lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy |
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What drugs should not be given with Allopurinol? Why?
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- Azathioprine and 6-Mercaptopurine (both normally metabolized by xanthine oxidase, which Allopurinol inhibits)
- Salicylates - all but the highest doses depress uric acid clearance |
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What is the mechanism and use of Febuxostat?
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- Inhibits xanthine oxidase
- Chronic gout drug (preventive) |
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What is the mechanism and use of Probenecid?
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- Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin)
- Chronic gout drug (preventive) |
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What NSAIDs can be used to treat gout? In what circumstance?
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- Naproxen and Indomethacin
- Acute gout flares |
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How can glucocorticoids be administered? In what circumstance?
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- Oral or intra-articular (into the joint)
- Acute gout flares |
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What is the mechanism and use of Colchicine? Side effects?
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- Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing leukocyte chemotaxis and degranulation
- Acute and prophylactic value for gout - GI side effects |
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What are the types of TNF-α inhibitors?
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- Etanercept
- Infliximab - Adalimumab |
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What are the characteristics of all TNF-α inhibitors? Why?
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Predispose to infection, including reactivation of latent TB, since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes
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What is the mechanism of Etanercept?
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- Fusion protein (receptor for TNF-α + IgG1 Fc portion) produced by recombinant DNA
- Etaner"CEPT" is a TNF decoy reCEPTor |
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What are the clinical uses of Etanercept?
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- Rheumatoid Arthritis
- Psoriasis - Ankylosing Spondylitis |
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What is the mechanism of Infliximab?
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Anti-TNF-α monoclonal antibody
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What is the mechanism of Adalimumab?
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Anti-TNF-α monoclonal antibody
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What are the clinical uses of Infliximab and Adalimumab?
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- Inflammatory Bowel Disease
- Rheumatoid Arthritis - Ankylosing Spondylitis - Psoriasis |