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13 Cards in this Set
- Front
- Back
1. What is the end product of purine metabolism in humans?
2. What plasma concentration of uric acid is considered hyperuricemia? |
1. Uric Acid
2. 6.8 mg/dl |
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1. Which drugs cause hyperuricemia and how do they do this?
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1. Diuretics: Interfere with uric acid secretion
Loops - Ethacrynic acid, Furosemide, Bumetanide Thiazides - Hydrochlorothiazide, Indapamide, Metolazone K+ Sparing - Amiloride |
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How do the following cause hyperuricemia?
1. Alcohol oxidation 2. Anticancer alkylating agents (Cisplatin, Vincristine, Cyclophosphamide) 3. Immunosuppressant Cyclosporine 4. Antiparkinson's Levodopa (L-Dopa) 5. bronchodilator Theophylling 6. Antifungal - Ketokonazole 7. Anti-TB Pyrazinamide, Ethambutol |
1. Upsets NAD/NADH --> Lactate production --> Competes with uric acid for excretion sites
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Gout: Drugs for Termination of the Inflammatory Acute Flare
Why not use Aspirin? |
NSAIDs – Indomethacin, Ibuprofen
Colchicine Corticosteroids ACTH Don't use Aspirin because of renal effects --> Salicylic acid competitively binds to organic acid receptors--> Causes decreased renal excretion |
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Corticosteroids:
Prednisone (Po) Triamcinolone (intra-articular) MOA |
Suppress synthesis of cytokines
Suppress movement and action of lymphocytes, eosinophils, and mast cells |
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Colchicine
1. MOA 2. Use 3. When should it be taken? How long does it take to work? 4. Tox |
1. Binds to tubulin --> Inhibits granulocyte motility
Decreses: Phagocytosis, granule release, granulocyte lysis, cytokine release 2. Acute phase of Gouty arthritis Prophylactically prevents or reduces the intensity of acute attacks 3. Take w/in 12 hours Relief w/in 48 hours 4. Gi - diarrhea, NV, ab pain Alopecia, Marrow depression, peripheral neuritis Hemorrhagic gastroenteritis, vascular damage, nephrotoxicity, ascending paralysis of the CNS |
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ACTH
1. MOA 2. Use 3. TOX |
1. Interfere with white blood cell ability to engulf uric acid crystals
2. Rapid resolution of inflammatory symptoms (0.5 days) Alternative to NSAIDs and Colchicine in GI or Renal patients |
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Allopurinol (Suicide Inhibitor)
1. MOA 2. Use - How can we reduce incidence and severity of acute attacks? 3. TOX 4. What happens to Hypoxanthine and Xanthine that accumulate as a result of using Allopurinol? 5. Drug Interactions? |
1. Blocks Xanthine Oxidase (final enzyme in pathway that converts purines to uric acid)
2. Tx chronic gout - Use with Colchicine 3. NV, Diarrhea, Peripheral Neuritis, Marrow Depression, Liver Tox, Interstitial Nephritis Hypersensitivity - Pruritic, eruthematous, maculopapular rashes 4. End products accumulate and crystalize at high concentration. They are then more water soluble. 5. Inhibits oxidation of 6-mercaptopurine and azathioprine (need to decrease dosages) Inhibits metabolism of anticoagulants and probenecid |
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Febuxostat
1. MOA 2. Use 3. TOX |
1. Xanthine oxidase inhibitor
2. Chronic hyperuricemia in gout patients Extensive liver metabolism 3. Nausea, Joint Pian, Rash No need for dose adjustment in kidney patients |
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Probenecid
1. MOA 2. Use 3. TOX 4. Drug interaction |
1. Blocks secretion and reabsorption of uric acid at the PCT --> Loss of uric acid
2. Reduction of urate pool Retain antibiotics (Penicillin, Cephalosporin, Fluoroquinolones) 3. Increased likelihood of Uric Acid stones Nephrotic Syndrome Allergic Dermatitis, GI Irritation 4. Salicylates decrease effectiveness --> Compete for same secretion sites Probenecid increases blood levels of the above antibiotics |
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Sulfinpyrazone
1. MOA 2. Use 3. TOX |
1. Same as probenecid (Blocks secretion and reabsorption of uric acid at the PCT --> Loss of uric acid) BUT more potent
2. Reduction of urate pool 3. GI distress. GIVE WITH FOOD OR MILK Aggrivate or Reactivate ulcers Anemia, leukopenia, Agranulocytosis, Thrombocytopenia |
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1. Symptoms of Tumor Lysis Syndrome
2. What causes the hyperuricemia seen with this syndrome? 3. What is the result? 4. How can this be prevented? |
1. Hyperuricemia (5.7-20.3 mg/dl)
HyperK+, HyperP, HypoCa2+, Oliguric Renal Failure 2. Massive an rapid nucleic acid metabolism 3. Accumulation of uric acid crystals --> Acute Renal Failure 4. Hydration with Diuresis before chemo Add Furosemide and Allopurinol Na+HCO3- alkalinizes urine --> Improves solubility of urate in urine --> Less crystalization |
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Rasburicase
1. MOA 2. Use 3. TOX |
1. (Recombinant urate oxidase) Oxidizes formed uric acid --> Reduces urate levels
2. More effective than Allopurinol at lowering acute urate 3. |