15.3 - Gout And Gout Drugs

Front 1

Gout
- Precipitating factors

Back 1

1. obesity
1.5 - fasting, severe dieting
2. alcohol - beer and yeast
3. diuretics, other drugs
4. impaired renal excretion
5. high cell turnover
6. high seafood diet (50% more likely to get gout)
7. Organ meats; high meat diet (40% more likely to get gout)
8. Vegies high in purines do not increase risk of gout: peas, beans, mushrooms, cauliflower, spinach, asparagus
9. Dairy food reduced risk of gout
10. overall protein intake had no effect on getting gout

Front 2

Gout
- Prevalence
- Long term complications

Back 2

More males than females. 5-8% of caucasian males, much more prevalent in Pacific islanders and Maori populations.
1. Joint destruction, Tophi ("Tophaceous gout"), complete disability (v. preventable)
2. Urate nephrolithiasis, renal disease

Front 3

First attack of gout is usually like what?
What age group?

Back 3

- In big toe, or other part of foot
- Red, swollen
- May have systemic features, like septic arthritis, with fever, malaise, raised inflammatory markers
- Usually between age 40-60. If less than 30 need to investigate for cause: alcoholism, enzyme deficiency, etc. It does not occur in children unless there is a defect in urate metabolism

Front 4

Pathogenesis of gout
- Literally, what happens
- Where does uric acid come from
- How is uric acid eliminated?

Back 4

- Uric acid crystals precipitate; there must be a high conc in the blood at some stage, not neccessarily at diagnosis however
- Uric acid is formed in the liver from PURINES in DNA (~60%) and food (~40%)
- Uric acid is excreted renally (~66%) through active transport. Weak acidic drugs compete. It is 33% eliminated in feces.

Front 5

Which drugs can affect uric acid levels?
1. Compete for excretion (increase)
2. Uricosuric (decrease reabsorption of uric acid)

**N.B. any drug that causes a rapid change in uric acid levels can precipitate a gout attack

Back 5

1. TZDs, Loop diuretics, aspirin, cyclosporin, nicotinic acid, PYRAZINAMIDE, ethambutol
2. Fenofibrate, probenecid

Front 6

Gout
- When should you start treatment and what are the aims?

Back 6

1. Hyperuricaemia does not require treatment
2. Acute gout - provide symptom relief; diagnosis should be confirmed by arthrocentesis and infective cause should be excluded (e.g. septic arthritis)
3. Chronic gout - long term treatments have toxicities, consider the need for treatment carefully

Front 7

For acute gout, what is the treatment?

Back 7

Self treat ASAP: possiblity of reducing the DURATION of the attack. Use
1. NSAID - First choice, use "full dose" and continue for 1 week after gout has abated!!! (Avoid analgesic aspirin, may increase urates and worsen!)
2. Corticosteroids, where NSAIDs CI. Oral, IV or INTRA-ARTICULAR when only 1-2 joints involved
3. Colchicine - Third line; colchicine has a slow onset of effect, so use paracetamol while waiting
**TG says colchicine is second line, prednisolone third!!!

Front 8

Chronic gout, what is the treatment?
(a) urate lowering
(b) prevention

Back 8

1. Urate lowering treatment
(a) allopurinol, initiated with an NSAID and/or colchicine , after attack has subsided
(b) Probenecid alone; sometimes used with allopurinol for tophaceous gout
2. Prevention
Low dose NSAID or colchicine at the start of urate lowering treatment, to prevent gout which occurs in ~25%; Does not prevent disease progression; Use low dose colchicine>NSAID

Front 9

In renal impairment, what treatment is preferred?
(a) acute attack
(b) uric acid lowering

Back 9

Acute: Corticosteroids (Colchicine may accumulate and cause myelosuppression)
Chronic: Allopurinol dose needs to be reduced(Probenecid ineffective at <40ml/min)

Front 10

Colchicine
- Dose forms, brands
- MOA

Back 10

- Colgout, Lengout, 500mcg.100 tabs
- Inhibits neutrophil migration, chemotaxis, phagocytosis; reduces the inflammatory reaction to urate crystals

Front 11

Colchicine
- Indications & doses

Back 11

1. relief of gout pain
1mg stat. 500mcg q6h until pain relief occurs or toxicity. Max 2.5mg in 24hrs. Max 6g/course (4 days). Do not repeat within 3 days. [newer AMH/PI dosing]
TG recommends just: 0.5 q6-8h until relief
2. prevention of gout
0.5mg d-bd
3. prevention of gout when starting urate lowering treatment
0.5mg tds until target dose is reached (TG)
4. Pericarditis

Front 12

Colchicine
- Why are higher doses of colchicine "just not justified" (TG)

Back 12

Severe nausea, vomiting and diarrhoea are VERY COMMON

Front 13

Colchicine
- A/E

Back 13

Common: n/v, diarrhoea, abdo pain
Infrequent: GI haemorrhage
Rare: peripheral neuropathy, myelosuppression, alopecia, respiratory failure, arythmia

Front 14

Colchicine
- Contraindications
- Cautions
- Renal use
- Hepatic use
- Pregnancy/ BF

Back 14

- 1 CI: Hx of myelosuppression
- Caution: May exacerbate severe GI disease
- Renal: Halve the dose in patients with CrCl <50ml/min; CI in severe impairment
- Hepatic: CI in severe impairment (accumulation)
- Cat B2: Avoid, Ltd data
- BF: avoid, contact pregnancy info centre

Front 15

What NSAID is most used for gout?
what dose?

Back 15

Indomethacin
50mg tds in acute attack for up to 5/7 (until symptoms abate), then 25mg tds until attack is gone

25mg bd for prevention / chronic gout

Front 16

Probenecid
- Dose form, brand

Back 16

Pro-Cid, 500mg.100 tab

Front 17

Pro-Cid
- MOA
- Indications

Back 17

- Increased renal excretion of gout by blocking reabsorption
- Reduces renal excretion of some drugs (e.g. penicillins)
- Urate lowering (gout)
- Adjunct to beta-lactam ABX treatment (penicillins and some cephalosporins)
- Adjunct to cidofovir treatment for CMV retinitis in HIV

Front 18

Pro-Cid
- Contraindications 4
- Considerations 1
- RI / HI
- Preg
- BF

Back 18

CI: gout attack, uric acid kidney stones, allergy, HISTORY OF BLOOD DYSCRASIAS
Caution: avoid in children <2
RI: Reduced effect if crcl <30-50ml/min, avoid
Preg: B2: In preg/BF contact preg info centre

Front 19

Pro-Cid
- A/Es

Back 19

common: rash, nausea, vomiting
infrequent: uric acid kidney stones, urinary frequency
rare: dyscrasias, SJS, HEPATIC NECROSIS

Front 20

Pro-Cid
- Dosing in gout
- When to stop?

Back 20

Gout prevention
250mg bd for 1 week; 500mg bd; increase up to 1g bd after 8 weeks (Titrate by urate conc)

Reduce dose by 500mgd every 6 months to lowest effective dose

Front 21

Pro-Cid
- ABX dosing

Back 21

- 500mg qid for duration of treatment
- 1g as a single dose for gonorrhoea with oral ABX; or 30 min before parenteral ABX

Front 22

Pro-Cid
- Counselling (2[4] important points!!)

Back 22

1. Take with FOOD to avoid stomach upset, and with plenty of WATER, to prevent kidney stones

2. More likely to get a gout attack initially. Do not take aspirin - reduces effect of probenecid

Front 23

What else can be done to reduce kidney stones with probenecid?

Back 23

Urinary alkalinisers can be used, prn.

Front 24

What monitoring of Pro-Cid is required>

Back 24

RF
CBC

Front 25

What if an acute attack of gout occurs with Probenecid?

Back 25

Continue treatment with Pro-Cid

Front 26

Is Pro-Cid permitted in sport?

Back 26

No! it may be used to mask detection of banned substances

Front 27

Probenecid - Drug interactions

Back 27

1. Reduces excretion of weak acids: penicillins, cephalosporins, sulfonylureas, rifampicin, some HIV drugs, NSAIDs (Clinical significance is not established)
- Ketorolac CI
- MTX should be avoided
2. Drugs reducing uricosuric effect: Aspirin

Front 28

Colchicine - Drug Interactions (3)

Back 28

1. Erythromycin, Clarithromycin concentrations are increased; caution
2. Cyclosporin toxicity increased: more GI upset, myopathy, renal and hepatic toxicity; avoid or monitor closely and reduce dose
3. Decreases efficacy of interferon alpha; avoid

Front 29

Allopurinol
- brands, dose forms

Back 29

300mg.60 (Allosig, Zyloprim, Allohexal, Progout)
100mg.100 (Progout, Allohexal)
100mg.200 (Allosig, Zyloprim)

Front 30

Allopurinol
- Mode of action
- Indications

Back 30

Allopurinol --> Oxypurinol, which inhibits xanthine oxidase, reducing production of uric acid
- Indicated for hyperuricaemia secondary to chemotherapy/radiotherapy
- Urate lowering treatment/prevention of gout

Front 31

Allopurinol
- CI
- Cautions
- RF/LF
- PREG/BF

Back 31

Allergy, initiation in acute attack, haemochromotosis

Caution: Azathioprine and mercaptopurine doses need reduction by 66-75%
RI: reduce, risk of accumulation (100mg d if mod, 100mg q48h, if severe RI)
Preg: B2, little data
BF: Are excreted in milk but no A/Es reported so far

Front 32

Allopurinol
- A/Es

Back 32

Common: maculopapular/itchy rash
Infrequent: n/v, taste disturbance,vertigo, drowsy
Rare: hepatotoxicity, SHS, blood dyscrasias, nephrolithiasis

Front 33

Allopurinol
- dosing

Back 33

Gout:
100mg d; increase monthly by 100mg according to response (usually 100-300mg d)
RI: 100mg d
Severe RI: 100mg every 2nd day

Prevention of hyperuricaemia due to tumour lysis syndrome:
600-800mg d, starting 1-3 days prior to treatment
Children: up to 600mg d

Front 34

Allopurinol
- Counselling

Back 34

1. With food
2. Drink lots of water to prevent kidney stones
3. Stop and immediately report signs of dyscrasias/exfioliative dermatitis: swollen lips or mouth, persistent fever, sore
throat & RASH (even though common)
4. L12: dizzy or drowsy

Front 35

Allopurinol
- Drug interactions (3)

Back 35

1. 6-MP, Azathioprine
2. Increases conc of theophylline; monitor
3. Be aware of increased risk of rash with amoxycillin and ampicillin