Pharmacology - Gout, Hyperuricaemia

Question 1

What are the drugs used to treat gout?

Answer 1

• NSAIDs
• Glucocorticoids
• Colchicine (leukocyte motility inhibitor)
• Allopurinol / Febuxostat (Uric acid synthesis inhibitor)
• Probenecid (Uricosuric agent)

Question 2

At what plasma concentration does urate precipitate?

Answer 2

> 7 mg/dL

Question 3

What are risk factors of gout?

Answer 3

Ageing
Diet (high in purines)
Hypertension
Diabetes
Hyperlipidaemia

Question 4

What are some common drug causes of hyperuricaemia?

Answer 4

Thiazide/loop diuretics
Low-dose aspirin
Ciclosporin

Question 5

Which compartment of the immune system responds to the formation of uric acid crystals, leading to inflammation?

Answer 5

Phagocytes (neutrophils, macrophages)

Question 6

What do immune cells do when they are activated by the formation of uric acid crystals?

Answer 6

Cytokine production;
Adhesion & Trafficking

Question 7

Which molecules are released when phagocytes fail to phagocytose the crystals? What is their role?

Answer 7

Leukotriene B4
Prostaglandins (PGE)
Free radicals

To recruit more phagocytes and increase vascular permeability.

Question 8

What is the MoA of NSAIDs in gout?

Answer 8

Inhibit production of prostaglandins and urate crystal phagocytosis.

Question 9

What is the MoA of Colchicine in gout?

Answer 9

1. Binds to tubulin and prevents tubulin polymerization into microtubules.
2. Inhibits leukocyte migration and phagocytosis.
3. Inhibits Leukotriene B4 and PG production.

Question 10

[Side effects] Colchicine

Answer 10

N/V/D
Abdo pain
Muscle weakness
Unusual bleeding
Pale lips
Change in urine amount

Question 11

What is the MoA of Allopurinol / Febuxostat in gout?

Answer 11

Decrease uric acid production by inhibition of Xanthine Oxidase.
Target: <6.0 mg/dL

Question 12

[Side Effects] Allopurinol / Febuxostat

Answer 12

[Unique]
Diarrhoea
Dark urine
Jaundice
Fever
Sore throat

Skin rash
N/V
Stomach pain

Question 13

What are the risk factors for Side effects for Xanthine Oxidase inhibitors?(esp. Allopurinol)

Answer 13

Renal impaired (CrCl <60ml/min)
Thiazide therapy
HLA-B*58:01 genotype (Han Chinese, Thai, Korean)

Question 14

What is the MoA of Probenecid in gout?

Answer 14

• inhibits proximal tubule anion transport
• inhibit uric acid Reabsorption (by solute carrier family 2 and 22)
• increases uric acid Excretion

Question 15

[Side Effects] Probenecid

Answer 15

[Unique]
Painful urination
Lower back pain
Allergic reactions / rash

N/V

Question 16

What Precautions will you advise patients to take for Probenecid?

Answer 16

• Drink plenty of water (minimizes renal stone formation).
• keep urine pH >6.0 by taking alkaline (eg. potassium citrate)