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
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
