Pharmacology - Uric Acid

Front 1

1. What is the end product of purine metabolism in humans?

2. What plasma concentration of uric acid is considered hyperuricemia?

Back 1

1. Uric Acid

2. 6.8 mg/dl

Front 2

1. Which drugs cause hyperuricemia and how do they do this?

Back 2

1. Diuretics: Interfere with uric acid secretion
Loops - Ethacrynic acid, Furosemide, Bumetanide
Thiazides - Hydrochlorothiazide, Indapamide, Metolazone
K+ Sparing - Amiloride

Front 3

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

Back 3

1. Upsets NAD/NADH --> Lactate production --> Competes with uric acid for excretion sites

Front 4

Gout: Drugs for Termination of the Inflammatory Acute Flare

Why not use Aspirin?

Back 4

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

Front 5

Corticosteroids:
Prednisone (Po)
Triamcinolone (intra-articular)

MOA

Back 5

Suppress synthesis of cytokines
Suppress movement and action of lymphocytes, eosinophils, and mast cells

Front 6

Colchicine

1. MOA

2. Use

3. When should it be taken? How long does it take to work?

4. Tox

Back 6

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

Front 7

ACTH

1. MOA

2. Use

3. TOX

Back 7

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

Front 8

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?

Back 8

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

Front 9

Febuxostat

1. MOA

2. Use

3. TOX

Back 9

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

Front 10

Probenecid

1. MOA

2. Use

3. TOX

4. Drug interaction

Back 10

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

Front 11

Sulfinpyrazone

1. MOA

2. Use

3. TOX

Back 11

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

Front 12

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?

Back 12

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

Front 13

Rasburicase

1. MOA

2. Use

3. TOX

Back 13

1. (Recombinant urate oxidase) Oxidizes formed uric acid --> Reduces urate levels

2. More effective than Allopurinol at lowering acute urate

3.