Drugs used in gout

Question 1

What is gout?

Answer 1

Gout is a common form of inflammatory arthritis that is very painful. It usually affects one joint at a time (often the big toe joint). There are times when symptoms get worse, known as flares, and times when there are no symptoms, known as remission.

Question 2

How are drugs used in gout classified?

Answer 2

I. For treatment of acute gout
NSAIDs: Indometacin, ibuprofen,
naproxen, ketoprofen etc.
Colchicine
Glucocorticosteroids

II. For prevention of acute gout
1. Inhibitors of uric acid synthesis
Allopurinol
Febuxostat
2. Promoters of uric acid excretion or
inactivation
Sulfinpyrazone
Rasburicase

Question 3

What is Colchicine?

Answer 3

Plant alkaloid of the autumn crocus (Colchicum autumnale)

Question 4

What is the pK, PD, ADR, and clinical use of colchicine?

Answer 4

PK
◦ Administration – oral
◦ Metabolites – in the bile and urine

PD
◦ Relieves pain and inflammation associated with gout 12-24 hours after administration
◦ Mechanism of action:
◦ Binds to the intracellular protein tubulin, thereby preventing its polymerization into microtubules and leading to
the inhibition of leukocyte migration to the joints (Colchicine-treated neutrophils develop a ‘drunken walk’);
◦ It also inhibits the formation of LTB4 and IL-1β.

ADR
◦ Acute: GIT – nausea, vomiting, and abdominal pain; diarrhea; at high dose –
gastrointestinal bleeding and renal failure
◦ Chronic: agranulocytosis, alopecia, peripheral neuropathy

Clinical use
◦ Specific activity in gout – both to prevent and to relieve acute attacks

Question 5

What is allopurinol? (what are the PK, mechanism of action, ARD, drug interactions, and clinical use)

Answer 5

PK
◦ Oral administration
◦ It is metabolized by xanthine oxidase

Mechanism of action
◦ Inhibition of xanthine oxidase and
reduced synthesis of uric acid

ADR
◦ Hypersensitivity reactions (skin rashes)
◦ GIT: nausea and diarrhea
Drug interactions
◦ Inhibits the metabolism of certain anticancer drugs(6-MP, azathioprine) and
increases their toxicity

Clinical use
◦ Gout – for prevention of attack

Question 6

What is Febuxostat? (what are the ADR and clinical uses?_

Answer 6

A potent and selective inhibitor of xanthine
oxidase
Oral use

ADR (well tolerated)
• Liver function abnormalities
• Diarrhea, nausea, headache

Clinical use
• Gout – for prevention of attack

Question 7

What are some examples of promotors of uric acid excretion or inactivation?

Answer 7

Sulfinapyrazone

Rasburicase

Question 8

What is the PK, mechanism of action, ADR, and clinical use of sulfinpyrazone?

Answer 8

PK
◦Oral administration

Mechanism of action
◦ Uricosuric drug – inhibits reabsorption of uric acid in the proximal
tubules

ADR
◦ GIT: gastric ulcers

Clinical use
• Gout – for prevention of attack

Question 9

What is the PK, mechanism of action, ADR, and clinical use of Rasburicase?

Answer 9

Rasburicase
A recombinant form of the enzyme urate oxidase

PK
• IV infusion
Mechanism of action
◦ Converts uric acid to water-soluble allantoin which is easily excreted
in the urine

ADR
◦ Hypersensitivity reactions

Clinical use
◦ Prevention and treatment of acute hyperuricemia in patients with
hematological malignancy at risk of rapid lysis.