Gout

Question 1

Gout

Answer 1

Gout is a disorder of purine metabolism, that occurs when uric acid, the breakdown product of purine metabolism, crystallizes in joints and tendons and surrounding tissues.

monosidium urate crystals trigger local inflammation

Question 2

tophi

Answer 2

a deposit of monosodium urate crystals in people with longstanding high levels of uric acid in the blood.
Tophi are pathognomonic for the disease gout.

Question 3

pre-disposing factors to a gouty attack

Answer 3

high levels of uric acid (can also be normal)
cooler body temps
low level of hydration
physical trauma and surgery

Dietary causes account for 10-15% of gout flare-ups and include a strong association with the consumption of alcohol, fructose- sweetened drinks, meat, and seafood.

Question 4

concomitant conditions

Answer 4

Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid levels, occurs in nearly 75% of all gout cases.

Question 5

Treatment of gout

Answer 5

• NSAIDs
• Steroids
• Colchicine
• Prophylactic treatment options include:
• Colchicine
• Allopurinol
• Probenecid

Question 6

Indomethacin/ Indocin

Answer 6

• Category: Non-steroidal anti-inflammatory drug (NSAID)
• Indication: Gout, arthritis, bursitis, migraine headache, hemicrania, pain and swelling.
• MOA: COX-I and COX-II inhibition
• Char: Generally administered as a PO tablet
or capsule. Syrup, suppository and IM dosing routes are also available.

Question 7

Usual dosage forms of Indomethacin

Answer 7

Tablets or capsules 25 and 50 mg Modified-release Capsules 75 mg Syrup (25 mg/5ml)
Suppositories 50 and 100 mg Injectable 50 mg for I.M. injection
Acute gouty arthritis is treated with 50 mg every 8 hours for 3 to 5 days.

Question 8

C/I and caution with indomethacin

Answer 8

Contraindications
Allergy to Indomethacin, aspirin, or other NSAIDs
Patients with nasal polyps reacting with an angioedema to other NSAIDs
Children under 2 years of age (with the exception of neonates with patent ductus arteriosus) Severe pre-existing renal and liver damage

Use with caution in patients with
History of ulcer disease
Bleeding tendencies of unknown origin (Indomethacin inhibits platelets aggregation) Parkinson’s disease, epilepsy, psychotic disorders (Indomethacin has been reported as possibly causing worsening symptoms in these conditions)
Concurrent use of potassium sparing diuretics
Significant hypertension

Question 9

Indomethacin/ Indocin SE

Answer 9

• Side effects: bleeding, gastritis, PUD, may exacerbate hypertension or CHF. Use with caution in patients with preexisting renal and/or liver disease.
• The use of Indomethacin and all NSAIDs should be avoided in patients with a hx of allergy to Indomethacin, aspirin and other NSAIDs.
• Avoid use in patients with history of asthma and nasal or sinus polyps.

Question 10

Samter’s triad

Answer 10

a medical condition consisting of asthma, aspirin and NSAID sensitivity, and nasal/ethmoidal polyposis.

It usually begins in young adulthood (twenties and thirties are the most common onset times) and may not include any other allergies.

caused by an anomaly in the arachidonic acid cascade which leads to increased production of cysteinyl leukotrienes,

Question 11

first line tx for Gout

Answer 11

NSAIDs are the usual first-line treatment for gout.

While Indomethacin has historically been the most commonly used NSAID, an alternative, such as Ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness.

For those at risk of gastric side effects from NSAIDs, it is not uncommon for a proton pump inhibitor to be added to the treatment regimen.

Question 12

Cortisone injection

Answer 12

• Category: Steroid
• Indication: Cortisone injections are used to
give short-term pain relief and reduce the swelling from inflammation of a joint, tendon or bursa as well as for marked allergic reaction or post-epinephrine treatment of anaphylaxis.
• MOA: decreases inflammation by inhibiting pro-inflammatory proteins.
Char: Intra-articular (IA) injection, also available in PO, IM, IV, spray and topical formulations.

Question 13

Cortisone SE

Answer 13

• Side effects: Use of cortisone has a number of potential systemic side effects: hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhea, cataracts and glaucoma, among other problems.

Question 14

before using cortisone injection…

Answer 14

Testing the joint fluid is especially important if the diagnosis is uncertain.

• Before a joint is injected with a steroid, joint fluid may be removed for testing.

Question 15

Colchicine

Answer 15

• Category: Mitotic inhibitor
• Indication: Gout – both for acute flares
and for prophylaxis.
• MOA: Colchicine inhibits microtubule
polymerization by binding to tubulin, one of the main constituents of microtubules. The availability of tubulin is essential to mitosis therefore mitosis is inhibited the process in affected cells.
Colchicine also inhibits neutrophil motility and neutrophil activity, resulting in an anti-inflammatory effect.
• Char: PO

Question 16

Colchicine SE

Answer 16

• Side effects: GI upset, anemia, neutropenia,
hair loss, hair loss, peripheral neuropathy. Colchicine overdose symptoms include: vomiting, diarrhea, acute renal failure and possible hypovolemic shock. No specific antidotes are known.

Colchicine has a relatively low therapeutic index

Question 17

Allopurinol/ Zyloprim

Answer 17

• Category: Purine analog
• Indication: Hyperuricemia, gout,
prophylaxis against tumor lysis syndrome
• MOA: Xanthine oxidase inhibitor
• Char: PO
• Side effects: Nausea, vomiting, skin rash,
SJS, Hypersensitivity syndrome consists of fever, skin rash, eosinophilia, hepatitis and decreased renal function.


Question 18

BAD SE from Allopurinol

Answer 18

• Allopurinol has rare but potentially fatal adverse effects involving the skin.
• The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsened renal function, and, in some cases, allopurinol hypersensitivity syndrome.
• Allopurinol is one of the drugs commonly known to cause Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TENS), two life-threatening dermatological conditions.

Question 19

Uricosurics

Answer 19

• Uricosuric medications are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma
. In general, this effect is achieved by action on the proximal tubule of the kidney.
By decreasing plasma uric acid levels, uricosurics help to dissolve these crystals, while limiting the formation of new ones.
However, the increased uric acid levels in urine can contribute to kidney stones.

Question 20

Probenecid/Probalan

Answer 20

• Category: Uricosuric
• Indication: Hyperuricemia, gout,
• MOA: Probenecid works by interfering
with the kidneys’ organic anion transporter (OAT), which reclaims uric acid from the urine and returns it to the plasma. Thus, the tubular reabsorption of uric acid is decreased which serves to increase the urinary excretion of uric acid.
• Char: PO
**still used to increase antibiotic concentrations in serious infections.

Question 21

Probenecid/Probalan SE

Answer 21

• Side effects: GI upset, gastritis, nausea,
vomiting. Anemia, leukopenia and possible hemolytic anemia, particularly in patients with glucose -6- phosphate dehydrogenase deficiency. Possible drug induced hepatitis, dizziness.
• May cause the formation of uric acid renal stones, particularly in patients with renal insufficency.
• Exacerbation of gout following therapy with Probenecid may occur. In such cases, Colchicine or other appropriate therapy is advisable.
• In patients on Probenecid the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of Probenecid.