Gout

Question 1

Aim to treat acute attacks of gout

Answer 1

Aim –> control pain and limit joint inflammation

Question 2

Aim to treat long-term managment of chronic gout

Answer 2

Aim –> modify purine metabolism or excretion to achieve normal concentrations of plasma urate

Question 3

drugs used to treat an acute goute attack

Answer 3

1. NSAIDs (e.g. ibuprofen, naproxen, indomethacin)
   - Selective NSAIDs –> in case of GI bleeding history.
   -Aspirin is contraindicated in Gout.
   2. Microtubule inhibitor –> e.g. colchicine is useful if NSAIDs are contraindicated.
   3. Glucocorticoids –> e.g. hydrocortisone {oral, intramuscular or intra-articular} is an alternative to NSAIDs and colchicine.
   4. Combinations –> used in severe acute attacks with polyarticular involvement.

Question 4

cateogory of Ibuprofen/ Naproxen/ Indomethacin

Answer 4

NS-NSAIDS

Question 5

Indication of Ibuprofen/ Naproxen/ Indomethacin

Answer 5

1. Used in patients with no GI bleeding history.
   note:
   * S-NSAIDs are used in case of a patient with GI
   bleeding history –> celecoxib

Question 6

S-NSAIDs used in case of a patient with GI bleeding history?

Answer 6

celecoxib

Question 7

MoA of Ibuprofen/ Naproxen/ Indomethacin

Answer 7

Effective in inhibiting the
inflammation of acute
gouty arthritis.

Question 8

PK/PD of indomethacine/ Ibuprofen/Naproxen

Answer 8

Act through the reduction of prostaglandins formation and the inhibition of crystal phagocytosis by macrophages.

Question 9

category of Clochicine

Answer 9

Microtubule Inhibitor

Question 10

Indication of Colchicine

Answer 10

1. Acute attacks of gout.
2. Lower doses are used to prevent attacks of gout in patients with history of multiple acute attacks.

Question 11

MoA of Colchicine

Answer 11

A selective inhibitor of microtubule assembly – ↓ microtubule polymerization.

Question 12

AE of Colchicine

Answer 12

Acute use:
1. Nausea, vomiting, diarrhea and GI pain.

Longer use:
1. Hepatic necrosis, acute renal failure, hematuria, (rarely may cause alopecia, myelosuppression and
peripheral neuropathy).
–> Can severely damage the liver and kidney -> monitoring patient is a MUST.

Question 13

PK/PD of Colchicine

Answer 13

1) Given for prophylactic treatment when drugs for chronic management of gout
are introduced.
2) Colchicine doses required to treat acute attacks cause significant GI disturbance
(abdominal pain and diarrhea).

Question 14

Category of Hydrocortisone

Answer 14

Natural Glucocorticoid

Question 15

indication of Hydrocortisone in the Tx of gout

Answer 15

Used as an
alternative to
NSAIDs and
colchicine.

Question 16

MoA of Hydrocortisone

Answer 16

reduce the synthesis of inflammatory mediators in the gouty joint (intraarticular injections).

Question 17

drugs used to treat Chronic gout

Answer 17

1) 1st line: Xanthine oxidase inhibitors –> reducing the conversion of purines to uric acid by Xanthine oxidase (e.g. allopurinol or
Febuxostat)
2) 2nd line; Uricosuric drugs –> accelerating renal excretion of uric acid (e.g. probenecid or sulfinpyrazone)

Question 18

Category of Allopurinol

Answer 18

Xanthine oxidase inhibitors

Question 19

Indication of Allopurinol

Answer 19

1st line treatment for Chronic Gout
–> Administered in combo with NSAIDs or Colchicine to avoid and acute attack.

Question 20

MoA of Allopurinol

Answer 20

Inhibition of xanthine
oxidase (XO) –> ↓ uric acid production

Question 21

PK/PD of Allopurinol

Answer 21

1) A prodrug –> given orally and is well absorbed.
2) Its half-life is 2-3h –> its active metabolite alloxanthine has a half-life of 18 – 30 h.
3) Renal excretion.
4) It inhibits the metabolism of azathioprine and 6-mercaptopurine (6-MP), drugs that depend on XO for their elimination.
5) increases the production of Xanthine and Hypoxanthine –> ↓ uric acid production

Question 22

Adverse effects of Allopurinol

Answer 22

–> Formation of renal stones is inhibited
(hypoxanthine stones might be formed).

Toxicities:
1. GI disturbances, allergic reactions (rashes), peripheral neuropathy, vasculitis, or bone marrow dysfunction.
2. Rare –> potentially fatal skin conditions
such as Stevens Johnson Syndrome (HLAB*5801 testing recommended in some
Asian populations).

Question 23

category of Febuxostat

Answer 23

Xanthine oxidase inhibitors

Question 24

indication Febuxostate

Answer 24

1. Used if allopurinol is not effective or not
   tolerated
   –> in combo with NSAIDs or colchicine.

Question 25

MoA of Febuxostat

Answer 25

A non-purine **reversible inhibitor of XO** that is more selective.

Question 26

PK/PD Febuxostat

Answer 26

1. Clinical trials show that it is more effective in treating chronic gout than Allopurinol. **2. Contraindicated in CV patients.**

Question 27

AE of Febuxostat

Answer 27

1. Some studies showed higher risk of **CVD deaths** Can cause liver function abnormalities, headache, and GI upset.

Question 28

Category of Probenecid/ Sulfinpyrazone

Answer 28

Uricosuric drugs

Question 29

Indication of Probenecid/ Sulfinpyrazone

Answer 29

Used orally to treat **chronic gout**, caused by **underexcretion of uric acid**

Question 30

MoA of Probenecid/ Sulfinpyrazone

Answer 30

1. **Compete with uric acid for reabsorption** by the weak acid transport mechanism (URAT1) in the proximal tubules --> This results in an **increased uric acid renal excretion** ***therofore, ineffective if patient has renal damage**

Question 31

AE of Probenecid/ Sulfinpyrazone

Answer 31

1. GI irritation, nephrotic syndrome. 2. Can **precipitate an attack of acute gout in early phase** of their action. --> To avoid this – simultaneously administering NSAIDs (e.g. indomethacin or colchicine). 3. **Crystallization** (kidney stones) might occur if high excretion of uric acid takes place. 4. **Alkalizing** the urine to reduce risk of stone formation. 5. Maintain high urine volume.

Question 32

PK/PD of Probenecid/ Sulfinpyrazone

Answer 32

1. At low doses, these drugs **compete with uric acid for secretion** by the tubule --> can elevate, rather than reduce, serum uric acid concentration. 3. **Not used in acute gout attack** – used in combination with **NSAIDs or colchicine** **4. Aspirin** --> causes **elevation of uric acid** levels by this mechanism – **contraindicated** **5. Inhibit the secretion** of a large number of other weak acids (e.g. **penicillin or methotrexate**) 6. These drugs are of no value in acute episodes. 7. Ineffective if GFR <50 mL/min (**renal failure**)

Question 33

Drugs contraindicated in Gout Tx, why?

Answer 33

Aspirin --> casues elevation of uric acid levels