Gout Pharm Flashcards
What is the clinical definition of hyperuricemia?
> 6.8mg/dL
What are 3 common pharmacological (2°) causes of gout?
1) Thiazide/Loop diuretics
2) Low-dose aspirin
3) Ciclosporin
What are the 2 goals of pharmacological treatment in gouty arthritis?
1) Relieve acute gouty attacks
2) Prevent recurrent gouty episodes
What are 2 non-modifiable and 3 modifiable risk factors for gouty arthritis?
Non-modifiable:
1) Aging
2) M:F 5:1 prevalence
Modifiable:
1) HTN
2) DM
3) HLD
Other than arthritis, what other common condition precipitates from hyperuricemia?
Nephrolithiasis
What are 3 main mechanisms of injury in an acute gouty attack?
1) Proteases
i) monocytes phagocytose urate crystals in joint
ii) release cytokines (eg. IL-1, TNF, IL-6
iii) proteases released from native joint synovium eg. chondrocytes after stimulation by cytokines
2) Lysosomal enzymes
i) complement activation → neutrophil chemotaxis
ii) phagocytosis of urate crystals → activation + lysis of neutrophils
iii) release of lysosomal enzymes
3) Free radicals, Prostaglandins, LTB4
i) i) complement activation → neutrophil chemotaxis
ii) phagocytosis of urate crystals → release of Free radicals, Prostaglandins, LTB4
What are 2 main agents/general approaches to treating gouty arthritis?
1) Acute relief of gouty arthritis
a) NSAIDs
b) Glucocorticoids
c) Colchicine
2) Prevention of gouty episodes (Urate-lowering therapy)
a) Xanthine oxidase inhibitors
b) Uricosuric agents
True or false: Urate-lowering medication eg. probenecid, allopurinol can be used in conjunction with NSAIDs in the treatment of acute gouty attack.
True but all URT must be used in caution during acute attacks.
What are 3 NSAIDs used for acute gouty attacks?
1) Naproxen
2) Indomethacin
3) Celecoxib
What is the moa of NSAIDs in the alleviation of acute gouty attacks?
Inhibit production of prostaglandins and urate crystal phagocytosis
What are 2 NSAIDs that are contraindication for the treatment of acute gouty attack?
1) Low dose aspirin
2) Salicylates (anti-uricosuric actions)
What is an example of a glucocorticoid used to treat an acute gouty attack?
Prednisolone
What is the typical presentation of an acute gouty attack?
Sudden onset of severe pain, swelling, warmth, and redness of a joint (typically very distal joints eg. big toe, knee)
What is the moa of colchicine in treating acute gouty attacks?
Binds to tubulin → prevent polymerisation into microtubules
∴ a) Inhibit leukocyte migration & phagocytosis
b) Inhibit leukotriene (LTB4) and PG production
What is the typical onset of action of colchicine?
24-36hrs
What are 4 AEs of colchicine?
1) Diarrhoea
2) N&V
3) Abdo pain
4) Muscle weakness
5) Unusual bleeding
6) Pale lips
7) Change in urine volume
What are 2 xanthine oxidase inhibitors used in the treatment of gout?
1) Allopurinol (1st line)
2) Febuxostat (2nd line)
What is the moa of allopurinol and febuxostat?
Anti-hyperuricemic agents
Inhibit xanthine oxidase
→ ↓metabolism of purines to uric acid
What are 3 indications of xanthine oxidase inhibitors (eg. allopurinol, febuxostat)?
1) Debilitating gout attacks
2) Chronic erosive arthritis
3) Urate nephrolithiasis
What are 3 AEs of xanthine oxidase inhibitors?
1) Skin rash
2) N&V
3) Diarrhoea
4) Fever
5) Sore throat
6) Abdo pain
7) Dark urine
8) Jaundice
What is the most life threatening AE of allopurinol?
Allopurinol hypersensitivity syndrome → Severe cutaneous adverse reaction (SCAR)
What are 3 risk factors for Allopurinol hypersensitivity syndrome?
1) Renal impairment (CrCl <60ml/min)
2) Thiazide therapy
3) HLA-B *58:01 genotype (most common in Han Chinese, Thai, Korean)
What is an example of a uricosuric agent used in gout?
Probenecid (solute carrier family 2 & 22 inhibitor)
What is the moa of probenecid?
1) Inhibits proximal tubule anion transport
2) Inhibits uric acid re-absorption
∴ ↑ Uric acid excretion
