Gout

Question 1

Indomethacin (3)

Answer 1

-Acute gout -Initial treatment (alternative to colchicine) -Use large dose for 1st 24 hours, then taper over 3-5 days

Question 2

NSAIDs (5)

Answer 2

-Acute gouty arthritis -Inhibit prostaglandin synthesis and urate crystal phagocytosis -Can use all agents except ASA -Use within 12 hours of onset, higher doses early -Oxaprozin: decreases UA level, not for patients with uric acid stones, not a uricosuric agent (TQ)

Question 3

Steroids (5)

Answer 3

-Acute gout -Initial treatment (for patients who can’t tolerate NSAIDs, kidney disease, GI bleeds) -Oral: 5-7 days then taper 7-14 days -Intra-articular: if 1-2 joints -ACTH-Corticotropin: IM, short DOA, needs repeat doses

Question 4

Colchicine (7)

Answer 4

-Alkaloid isolated from autumn crocus (TQ) -Anti-inflammatory: bind to tubulin preventing polymerization into microtubules -Inhibits leukocyte migration, phagocytosis, and formation of leukotriene B4, does NOT alter metabolism or excretion of urates -Uses: onset of acute attack, relieves pain and inflammation, prophylaxis (gouty arthritis, acute Mediterranean fever, sarcoid arthritis) -Doses: maximum oral dose is 1.8mg taken over a 1 hour period, maximum of 3mg/24hrs, IV: 2mg diluted with 20ml saline to minimize sclerosis of vein (max 4mg) -ADRs: N/V/D, GI toxicity (50-80%), hair loss, bone marrow depression, peripheral neuritis, myopathy, acute intoxication (burning thorat pain, bloody diarrhea, [TQ] shock, hematuria, oliguria) -Avoid alcohol

Question 5

Primary Uricosuric Agents (7)

Answer 5

-Probenecid and Sulfinpyrazone -MOA: affect transport in proximal tubule so less UA is reabsorbed and more is excreted -Uses: decrease pools of urate (tophi, several acute attacks, high plasma levels of UA), -Doses: therapy should not be started until 2-3 weeks after an acute attack (bc increase risk in uric stones) (TQ) -ADRs: GI irritation (sulfinpyrazone more), rash (probenecid causes allergic dermatitis, TQ), nephrotic syndrome (probenecid more), aplastic anemia -Avoid in patients who excrete large amounts of UA, could cause precipitation of UA calculi -Maintain large urine volume to avoid stone formation

Question 6

Fenofibrate (2)

Answer 6

-Lipid lowering agent, decreases renal tubular reabsorption of serum UA enhancing its renal excretion -Uricosuric effect independent of lipid lowering effect (it’s a secondary uricosuric)

Question 7

Losartan (3)

Answer 7

-Angiotensin receptor blocker -Acts a uricosuric (it’s a secondary uricosuric) -Raises urine pH so risk of supersaturation does not occur and nephropathy is less

Question 8

Allopurinol (5)

Answer 8

-Reduces UA synthesis by inhibiting xanthine oxidase -For under-excreters and overproducers -Uses: chronic tophaceous gout (TQ), when uricosurics are ineffective, recurrent renal stones, renal impairment, grossly elevated serum urate levels, an antiprotozoal -Dosing: most effective in young, give colchicine or NSAIDs during first weeks to prevent gouty arthritis -ADRs: GI (less than colchicine), pruritic maculopapular lesions, acute attacks of gouty arthritis, perpheral neuritis, necrotizing vasculitis, bone marrow depression, aplastic anemia, hepatic toxicity, interstitial nephritis, cataracts

Question 9

Febuxostat (4)

Answer 9

-Xanthine oxidase inhibitor for chronic management of hyperuricemia in patients with gout -Limited excretion in urine -Can block clearance of xanthine-based drugs like azathioprine and theophylline -ADRs: upper respiratory tract infections, muscle/CT symptoms, diarrhea

Question 10

Pegloticase (5)

Answer 10

-Pegylated urate oxidase compound that oxidizes urate to allantoin (high soluble, more readily excreted in urine) (TQ) -Also breaks down pre-existing uric acid which allopurinol does not -Uses: severe refractory gout, to offset ADRs treat with NSAIDs/Cochicine for first 6 months -ADRs: gout flares, nausea, contusions, nasopharyngitis, constipation, chest pain, vomiting, infusion reactions, anaphylaxis (premedicate with antihistamines/steroids) -Caution in CHF, and don’t use in patioent swith G6PD

Question 11

Rasburicase (2)

Answer 11

-Non-pegylated recombinant urate oxidase -Used for tumor lysis syndrome

Question 12

Overproduction of UA (2)

Answer 12

-Primary: specific enzyme defects -Secondary: myelo/lymphoproliferative disorders, mononucleosis, chornic hemolytic anemia

Question 13

Underexcretion of UA (2)

Answer 13

-Primary: idiopathic, familial juvenile gouty nephropaty -Secondary: chronic renal mass/kidney injury, hypertension, sickle cell anemia, hypothyroid, Down’s

Question 14

Hyperuricemia (4)

Answer 14

-Serum UA concentration more than 7-7.5 mg/dl -Super saturated concentration can precipitate into joint or tissue -Can be aymptomatic -Due to overproduction/underexcretion of UA

Question 15

Foods that increase hyperuricemia (6)

Answer 15

Purine-Containing Foods such as: -Meats (esp organs: liver, kidneys, sweetbreads), meat extracts, consomme, gravies -Beer -Anchoives, sardines, fish roes, herring -Yeast -Legumes -Mushrooms, spinach, asparagus, cauliflower

Question 16

Beneficial foods for those with gout (5)

Answer 16

-High complex carbs (whole grains, fruits, vegetables) -Low protein -No more than 30% of calories from fat -Dairy seems protective -Certain fatty acids like salmon flax, olive oil, and nuts may possess some anti-inflammatory benefits

Question 17

Drugs capable of inducing hyperuricemia and gout (10)

Answer 17

-Diuretics (TQ) -Salicylates -Cytotoxic drugs -Ethanol -L-Dopa (TQ) -Pyrazinamide, ethambutol (TQ) -Nicotinic acid (TQ), B12 -Cyclosporine (TQ) (PNC BLEEDS Cash)

Question 18

Gout Clinical Characteristics (6)

Answer 18

-Supersaturated synovial fluid causes urate crystal to form -Crystals engulfed by synoviocytes -This causes the release of inflammatory/chemotactic mediators -Mediators attract polymorphonuclear leukocytes into joint space and amplify the inflammatory process -In later phases, more macrophages arise, ingest urate crystals and release more inflammatory mediators -Patients will complain of pain, erythema, warmth, swelling, fever, leukocytosis, untreated lasts 3-14 days

Question 19

Acute Gout (3)

Answer 19

-Occurs in peripheral joints of lower extremities related to low temp combined with increased intra-articular urate concentration -At night water is reabsorbed from joint space leaving supersaturated solutions of urate which precipitates -Untreated: lasts 3-14 days

Question 20

Nephrolithiasis (5)

Answer 20

-10-25% of gout patients -50% of those whose renal excretion of UA exceeds 1100mg/day -Stones may be pure UA (radiolucent), UA/Ca oxalate, or pure Ca oxalate (radiopaque) -Predisposing factors: excessive urinary excretion of uric acid, acidic/concentrated urine -When acidic urine is satruated with UA, spontaneous precipitation of stones may occur

Question 21

Acute Gouty Arthritis (3)

Answer 21

-Initially one joint is affected (MTP), then insteps, ankles, heels, knees, wrist, fingers, elbows -Precipitating conditions: stress, trauma, alcohol ingestions, infection, surgery, rapid lowering of serum UA -Diagnosis: aspiration of synovial fluid and identification of intracellular crystals of monosodium urate monohydrate in leukocytes

Question 22

Acute Gouty Nephropathy (3)

Answer 22

-Urine flow is blocked by massive precipitation of UA crystals in collecting ducts and ureters -Can occur after chemo -Allopurinol reduces/prevents nephropathy

Question 23

Chronic Gouty Nephropathy (4)

Answer 23

-Caused by long-term deposition of urate crystals in renal parenchyma, microtophi may form -Hypertension and nephrosclerosis common -Hyperuricemia alone probably not harmful to kidneys -Irreversible

Question 24

Tophaceous Gout (2)

Answer 24

-Late complication of hyperuricemia -Tophi cause deformitis, damage soft tissue around deposits, cause joint destruction/pain, may lead to nerver compression syndromes (carpal tunnel)

Question 25

Treatment Goals for Gout (4)

Answer 25

-Distinguish hyperuricemia with gout from asymptomatic hyperuricemia -Terminate actue attack -Prevent future attacks and complications -Do NOT treat hyperuricemia during acute attack -T/F: in gout treatment, it is important to treat all types of hyperuricemia (false, TQ)

Question 26

Treatment Plan for Gout (3)

Answer 26

-Intitial treatment with fast acting NSAIDs (unless risk factors for their use) -Use within 12 hours of first symptoms for maximum efficacy -High doses early (24-48 hours)

Question 27

First line chronic therapy (4)

Answer 27

-Allopurinol or febuxostate -Probenecid as alternative -Monitoring every 2-5 weeks during dose titration -Target serum urate concentration: less than 6mg/dl

Question 28

Prophylactic Therapy

Answer 28

-After first episode (can be withheld if mild and responded to treatment) -Frequent attacks of gouty arthritis even if serum UA is normal -DOC: allopurinol (TQ) -Low-dose oral colchicine for patients with no tophi -Therapeutic objective is to reduce serum urate concentration below 6 mg/dl