Gout Drugs

Question 1

Probenecid

Answer 1

uricosuric drugs (increase rate of excretion of uric acid)
1. Inhibit reabsorption of urate from lumen of nephron in PCT & increase uric acid excretion
Opp than penicillin (I secretion into tubules, raise its plasma [ ])
2. Oral. 90% bound to albumin .

if given in subtherapy does= make matters worse & I uric acid secretion

Question 2

Sulphinpyrazone

Answer 2

1. inhibit uric acid reabsorption in PCT

if given in subtherapy does= make matters worse & I uric acid secretion

Question 3

Salicylates

Answer 3

1. inhibit secretion in doses w/in therapy range, produce increase in urate levels in blood
2. may exacerbate gouty arthritis & antagonize other uricosurics

Question 4

Allopurinol

Answer 4

1. Use: treat primary hyperuricemia of gout & hyperuircemia secondary to anti neoplastic therapy.
2. used long therm
3. if pt has gouty episode- continue therapy & treat acute episode with NSAID or colchin
4. Useful in pts w/ renal impairment or urat estones
5. MOA: reduce syn of uric acid by inhibiting xanthine oxidase. Analog to hypoxanthine. Competitive Inhibitor.

Question 5

Alloxanthine

Answer 5

1. effective non comp I of enz XO
2. Insolub urates & uric acid reduced in tissues, deposition of urates in tissue as trophi reverse & form renal stones inhibited

Question 6

Interactions

Answer 6

1. allopurinol increase half life of probenecid. Probenecid increase CL of alloxanthine thus a higher dose of allopurinol is required if pts is on both drugs.
2. Allopurinol decrease metabolism of azathiaprine & mercaptopurine.
   Doses of both must be reduced if given together w/ allopurinol as they are highly toxic
3. If allopurinol given w theophyline xanthine leads to increased accum of 1-CH3 xanthine (active metabolite)

Question 7

NSAID treatment- indomethacin

Answer 7

1. releive pain by inhibit inflamm response

2. interfere w/ PG syn

Question 8

Colchine

Answer 8

antimitotic agent
1. anti inflamm used in acute gouty arthritis
2. w/in 12 hrs pain & redness reduced
Not analgesic!
3. MOA: inhibit cell dividsion. Binds to tubulin so MT don’t form. Lead to inhibition of leukocyte migration into joints & mobility compromised.
Also blocks lipoxygenase enz (Leukotrient B4)
4. Oral & IV
Undergoes enterohepatic recirculation. Drug secreted into bile mediated by MDR prot pump.
Drugs which inhibit liver MDR prot like cyclosporine & verapamil= increase colchine fraction delivered to & remaining in sys circulation so won’t get into gut.
5. Severe GI toxicity! Reduces ADH as well.
6. Side effects: limit its chronic use
GI upset, diarrhea
myelosuppressive, agranulocytosis, aplastic anemia, myopathy, alopecia.