Gout Pharm

Question 1

What is the clinical definition of hyperuricemia?

Answer 1

> 6.8mg/dL

Question 2

What are 3 common pharmacological (2°) causes of gout?

Answer 2

1) Thiazide/Loop diuretics
2) Low-dose aspirin
3) Ciclosporin

Question 3

What are the 2 goals of pharmacological treatment in gouty arthritis?

Answer 3

1) Relieve acute gouty attacks
2) Prevent recurrent gouty episodes

Question 4

What are 2 non-modifiable and 3 modifiable risk factors for gouty arthritis?

Answer 4

Non-modifiable:
1) Aging
2) M:F 5:1 prevalence

Modifiable:
1) HTN
2) DM
3) HLD

Question 5

Other than arthritis, what other common condition precipitates from hyperuricemia?

Answer 5

Nephrolithiasis

Question 6

What are 3 main mechanisms of injury in an acute gouty attack?

Answer 6

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

Question 7

What are 2 main agents/general approaches to treating gouty arthritis?

Answer 7

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

Question 8

True or false: Urate-lowering medication eg. probenecid, allopurinol can be used in conjunction with NSAIDs in the treatment of acute gouty attack.

Answer 8

True but all URT must be used in caution during acute attacks.

Question 9

What are 3 NSAIDs used for acute gouty attacks?

Answer 9

1) Naproxen
2) Indomethacin
3) Celecoxib

Question 10

What is the moa of NSAIDs in the alleviation of acute gouty attacks?

Answer 10

Inhibit production of prostaglandins and urate crystal phagocytosis

Question 11

What are 2 NSAIDs that are contraindication for the treatment of acute gouty attack?

Answer 11

1) Low dose aspirin
2) Salicylates (anti-uricosuric actions)

Question 12

What is an example of a glucocorticoid used to treat an acute gouty attack?

Answer 12

Prednisolone

Question 13

What is the typical presentation of an acute gouty attack?

Answer 13

Sudden onset of severe pain, swelling, warmth, and redness of a joint (typically very distal joints eg. big toe, knee)

Question 14

What is the moa of colchicine in treating acute gouty attacks?

Answer 14

Binds to tubulin → prevent polymerisation into microtubules
∴ a) Inhibit leukocyte migration & phagocytosis
b) Inhibit leukotriene (LTB4) and PG production

Question 15

What is the typical onset of action of colchicine?

Answer 15

24-36hrs

Question 16

What are 4 AEs of colchicine?

Answer 16

1) Diarrhoea
2) N&V
3) Abdo pain
4) Muscle weakness
5) Unusual bleeding
6) Pale lips
7) Change in urine volume

Question 17

What are 2 xanthine oxidase inhibitors used in the treatment of gout?

Answer 17

1) Allopurinol (1st line)
2) Febuxostat (2nd line)

Question 18

What is the moa of allopurinol and febuxostat?

Answer 18

Anti-hyperuricemic agents
Inhibit xanthine oxidase
→ ↓metabolism of purines to uric acid

Question 19

What are 3 indications of xanthine oxidase inhibitors (eg. allopurinol, febuxostat)?

Answer 19

1) Debilitating gout attacks
2) Chronic erosive arthritis
3) Urate nephrolithiasis

Question 20

What are 3 AEs of xanthine oxidase inhibitors?

Answer 20

1) Skin rash
2) N&V
3) Diarrhoea
4) Fever
5) Sore throat
6) Abdo pain
7) Dark urine
8) Jaundice

Question 21

What is the most life threatening AE of allopurinol?

Answer 21

Allopurinol hypersensitivity syndrome → Severe cutaneous adverse reaction (SCAR)

Question 22

What are 3 risk factors for Allopurinol hypersensitivity syndrome?

Answer 22

1) Renal impairment (CrCl <60ml/min)
2) Thiazide therapy
3) HLA-B *58:01 genotype (most common in Han Chinese, Thai, Korean)

Question 23

What is an example of a uricosuric agent used in gout?

Answer 23

Probenecid (solute carrier family 2 & 22 inhibitor)

Question 24

What is the moa of probenecid?

Answer 24

1) Inhibits proximal tubule anion transport
2) Inhibits uric acid re-absorption
∴ ↑ Uric acid excretion

Question 25

What are 3 indications of probenecid?

Answer 25

1) When allopurinol is contraindicated in tophaceous gout (eg. AIS)
2) In increasingly frequent gouty attack
3) 2-3 weeks after an acute attack

Question 26

What are 3 AEs of probenecid?

Answer 26

1) N&V
2) Dysuria
3) Lower back pain
4) Allergic rxn
5) Rash

Question 27

What should patients taking probenecid be advised?

Answer 27

Plenty of fluid to minimise renal stone formation

Question 28

Why is alkaline administered to patients taking probenecid?

Answer 28

Keep urine pH>60 to reduce stone formation