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NR566 Week $ Study Guide_Chapter 25: Drugs Used in Treating Inflammatory Processes

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AIT Nursing (NR566)

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Thompson River University (TRU )

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chapter 25 drugs used in treating inflammatory processes
nr 566 week 4 study guide chapter 25 drugs used in treating inflammatory processes
gout medications drugs anti gout agents allopurinol z

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NR 566 Week 4 Study Guide
Chapter 25: Drugs Used in Treating Inflammatory Processes
Gout medications
Drugs:
Anti-gout agents: allopurinol (Zyloprim), colchicine, and febuxostat (Uloric)
Uricosuric agents: probenecid (Benemid) and sulfinpyrazone (Anturane)
o Peak incidence 70 to 79 years old, more common in men than women
o Gout in women occurs exclusively post-menopausal and is associated with HTN, renal insufficiency, and
diuretics
o Gout Syndrome: Caused by an alteration in purine metabolism: end product is uric acid
o Hyperuricemia and deposition of urate crystals in various tissues
o Four phases: asymptomatic hyperuricemia, acute gouty arthritis, inter-critical gout, and chronic tophaceous
gout
o Those with asymptomatic hyperuricemia do not require treatment (diet and lifestyle changes)
o Acute gout is characterized by sudden onset of pain, erythema, limited ROM, and swelling of the
involved joint
 50% of cases involve the first metatarsal joint of the great toe
o Key elements in Tx include management of the acute pain and use of antigout and uricosuric agents
o Pain: NSAIDS and corticosteroids

Pharmacodynamics
Antigout Drugs (allopurinol, colchicine, and febuxostat)
o Act to reduce the inflammatory process or to prevent the synthesis of uric acid
o Allopurinol and febuxostat inhibit xanthine oxidase: enzyme responsible for conversion of hypoxanthine and
xanthine to uric acid
o Allopurinol has a metabolite (alloxanthine): also an inhibitor of xanthine oxidase
o Allopurinol acts directly on purine metabolism, reducing the production of uric acid, without
disrupting biosynthesis of vital purines
o Allopurinol and febuxostat are the only drugs that act directly on the pathophysiological cause of gout
o Allopurinol decreases both serum and urinary uric acid in 2 to 3 days: dose dependent
 A week or more of Tx may be necessary before the full effects can be seen
o Febuxostat is used to treat hyperuricemia in patients with gout
o Goal is to have uric acid level of less than 6 mg/dL
o Can take 2 weeks or more to see the effects of febuxostat
o Colchicine: does not affect purine metabolism
o Binds to the microtubular proteins to interfere with the function of the mitotic spindles and inhibit
migration of granulocytes to the inflamed area
o Reduces lactic acid production by granulocytes: decreases deposition of uric acid
o Interferes with kinin formation and reduces phagocytosis
o Taken together: these actions decrease the inflammatory response to the deposited urate crystals
o Relives pain in acute attack: not an analgesic
o Its prophylactic, suppressive effect helps reduce the incidence of acute attack and relives patient’s
occasional residual pain and mild discomfort

Uricosuric drugs: probenecid (Benemid) and sulfinpyrazone (Anturane
o These drugs increase the rate of uric acid secretion in the urine

,o Both drugs inhibit renal tubular reabsorption of urate and thus increase the renal excretion of uric acid and
decrease serum uric acid levels.
o Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes reabsorption of
urate deposits
o Sulfinpyrazone competitively inhibits platelet prostaglandin synthesis: prevents platelet aggregation
(antithrombotic effects)
o Both drugs lack anti-inflammatory activity
o Most useful in patients with reduced urinary excretion of uric acid
o Not intended for Tx of acute attacks

Pharmacotherapeutics
o Allopurinol (Zyloprim) colchicine, probenecid (Benemid, and sulfinpyrazone (Anturane): poor urate
clearance in the presence of renal impairment
o Use with caution: renal function tests performed regularly to determine dosage
o Data is insufficient regarding febuxostat in renal impairment
o Allopurinol and colchicine: hepatotoxicity
o Not recommended for patients with severe hepatic dysfunction
o If anorexia, weight loss, or pruritus, evaluate LFTs
o For milder hepatic disorders: close monitoring of LFTs is required
o Colchicine, probenecid, and sulfinpyrazone: used cautiously in PUD or spastic colon
o GI ADRs from these drugs are likely to make these disorders worse
o Sulfa allergy: do not use probenecid and sulfinpyrazone: sulfa-based drugs
o Febuxostat, a xanthine oxidase inhibitor, is contraindicated in patients being treated with drugs requiring
xanthine oxidase for metabolism:
o Azathioprine, mercaptopurine, or theophylline
o Risk for toxicity
o When febuxostat is started there is a risk of a gout flare up: concurrently treat with NSAID or colchicine for
up to 6 months
o Allopurinol Preg Cat C: no adequate data
o Colchicine Category C PO and D when IV/IM
o Can cause fetal harm when administered to pregnant women
o Probenecid is Preg cat B
o Sulfinpyrazone: cat D: not much data for pregnant women
o Avoided in Pregnancy
o Febuxostat Cat C: no adequate studies in pregnant women
o These drugs are not indicated for use in children except in hyperuricemia associated with Tx of malignancy
(specialist care)
o Probenecid: retarding PCN or cephalosporin excretion in selected infections

ADRs
o GI ADRs: colchicine, probenecid, and sulfinpyrazone
o NVD, and ABD pain
o Particularly troublesome for patients with Hx of PUD or active PUD
o Hypersensitive reactions with sulfa allergy: probenecid and sulfinpyrazone
o Severe, anaphylactic reactions are rare and typically occur within several hours after first dose,
following prior use of the drug
o Allopurinol: maculopapular skin rash, sometimes scaly or exfoliative
o Incidence increased with renal disorders
o Skin reactions may be severe and sometimes fatal: d/c at first sign of rash

, o The most severe reactions include: fever, chills, arthralgia, cholestatic jaundice, eosinophilia, mild
leukocytosis, or leukopenia
o Patients on standard therapy with colchicine who have elevated plasma levels r/t renal function have
developed myopathy and neuropathy that resulted in weakness
o Often unrecognized and misdiagnosed as polymyositis or uremic neuropathy
o Proximal weakness and elevated creatinine kinase are generally present
o Resolves in 3 to 4 weeks was drug withdrawal
o Colchicine: induces reversible malabsorption of B12
o Febuxostat: risk of liver function abnormalities (40 mg/day) and nausea an arthralgia at 40 mg/day

Drug Interactions
o Colchicine: very few drug interactions
o Probenecid, allopurinol, and sulfinpyrazone: many drug interactions
o Always check the drug regimen before starting these drugs

Clinical Use and Dosing
Gout
Goal of therapy is urate level less than 6 mg/dL: doses are titrated upward until that goal is reached
o Colchicine PO: time honored drug for Tx of acute gouty attacks
o Efficacy is limited by ADRs
o Dose adjustments for impaired renal or hepatic function
o Use with caution in older adults
o Initial dose of 1.2 mg at the first sign of flare, followed by 0.6 mg 1 hour later (maximum 1.8 mg
over 1 hr)
 Articular pain and swelling usually abate within 12 hours and gone in 24 to 48 hours
o Preventive therapy
 for those with fewer than one acute attack per year is 0.6mg/d of colchicine for 3-4 days a
week
 For those with more than one acute attack per year dose is 0.6 mg every day
 Serious cases may require 1.2 to 1.8 mg/day
o Allopurinol: drug of choice for patient with Hx of urinary calculi, renal insufficiency, chronic tophaceous
gout, or high level of serum urate
o Doses of 200 to 300 mg/day for mild and 400 to 600 mg/day for moderately sever tophaceous fout
o Minimum effective dose is 100 to 200 mg/d and maximum dose is 800 mg/day
o Doses greater than 300 mg/day must be divided
o Dosage adjustments for patient with renal insufficiency are based on CCr values
o Febuxostat: indicated for chronic management of hyperuricemia in paitnets with gout
o Starting dose: 40 mg/day
 If serum uric acid is not lowered below 6 mg/dL after 2 weeks, dose increased to 80 mg/Day
o Taken w/o regard to food
o No dosage adjustment is needed for renal or hepatic impairment
o Periodic uric acid levels are drawn, the first a t 2 weeks of therapy
o LFTS should be tested at 2 and 4 months after starting therapy
o NSAID or colchicine should be given prophylactically for the first 6 months of febuxostat to prevent
acute gout flare
o Drugs that inhibit uric acid synthesis are more toxic, especially in older adults and should be reserved for
patients who “over produce urate”
o Those who excrete more than 800 mg/24 hours
o Probenecid: uricosuric agent of choice because of well-established safety and long duration of action

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