18 - Gout Flashcards
Define gout
A group of heterogenous diseases characterized by arthropathy resulting from the deposition of rate crystals in and around the joint
More common in ____
males
Peak incidence after ___ yo
40
Modifiable comorbidities for gout
- hyperuricemia
- hypertension
- obesity
- diabetes
- alcohol consumption (binge)
- high purine intake
- drugs
Non-modifiable comorbidities
- chronic kidney disease
- male gender
- age
- family history (genetics)
_____ and high uric acid levels are risk factors for each other.
hypertension
*another point to note is that the medications used to treat hypertension contribute to decreasing kidneys ability to excrete uric acid thus contributing to hyperuricemia
Risk of ______ may be related to chronic low grade inflammation associated with gouty arthritis and type 2 DM as “inflammasome activation disorders” in which monosodium rate and glucose respectively trigger increased processing of IL-Ib
diabetes
How can hyperuricemia promote renal disease?
bc the deposition of urate crystals in the kidney can cause interstitial inflammation and tubular injury, which impairs renal function.
controlling uric acid levels with rate lowering therapy can slow the progression of CKD
What dietary factors can increase uric acid level?
- high purine diet (meats and shell fish)
- decreased mild product intake
What serum uric acid level defines hyperuricemia?
> 480 umol/L in males
> 420 umol/L in females
Etiology behind hyperuricemia?
- overproduction
- underexcretion
What is uric acid?
- just a waste product
- it has no physiological function
- in many other species uric acid is further broken down (typically cats and dogs don’t develop gout) but in humans we do bc the degradation stops at uric acid
10-20% of patients with gout are due to _______ of uric acid
overproduction
How is overproduction of uric acid defined?
3.5 mol/day uric acid excretion while on a 5 day purine free diet
Possible etiologies of overproduction of uric acid?
- diet
- tissue/cell breakdown
- metabolic derangement
80-90% of patients with gout is due to _______
underexcretion
How is under excretion of uric acid defined?
< 3.5 mol/day uric acid excretion while on a 5 day purine free diet
What are some possible etiologies of under excretion?
Renal abnormalities
67% of uric acid is excreted by the kidneys
Describe the renal excretion of uric acid
- uric acid enters glomerulus
- most of this is reabsorbed
- you get 10% of the initial amount being excreted in the urine
- a lot of movement from uric acid in and out of the kidney
What factors alter renal excretion of uric acid?
- Decreased GFR
- Decreased active secretion of uric acid (salicylate, thiazides, acute alcohol, ketoacidosis, lactic acidosis)
- Increased post-secretory resorption (ex. dehydration, high dose ASA)
- Undefined (hypertension, hyperparathyroidism, cyclosporine)
How does temperature affect solubility of uric acid?
decreased temp = decreased solubility of uric acid
*why it precipitates in toe (cold extremely, distal part of body)
Why can you have high uric acid levels and not develop gout?
- need a joint to be damaged which makes it susceptible to uric acid precipitating at that joint level
- our toe undergoes a tremendous amount of stress and develops damage that we don’t address
What 2 things do you need to develop gout?
1) need high uric acid level
2) need susceptible joint
What is the Symkin hypothesis?
when you lay down, an acute gout attack will present
Describe an acute gouty attack
- Sudden onset of warmth, swelling, erythema, and unbearable joint pain
- 50% of first attacks are in toe only
- 90% will have involvement of toe joint sometime during their disease
- usually severe pain
- systemic symptoms such as fever, chills, malaise
- HAS TO BE SUDDEN
- if pt says their toe joint has been hurting for a few days - not a typical presentation
10% of first acute gouty attack involve how many joints?
2 or more
How long do untreated symptoms last in an acute gouty attack?
3-14 days before spontaneous recovery
List 2 reasons why peripheral joint sites are more common for gouty attacks
- decreased temp
- tend to have more joint damage
Precipitating factors of a gout attack?
- stress or trauma to joint
- binge drinking (high purine content)
- infection
- surgery
- rapid lowering of serum uric acid
- drugs that increase uric acid
About half the time, ppl with gouty attack with have ____ uric acid level
normal
- uric acid in plasma is redistributed into joint (so brings down plasma uric acid level)
- if they have a normal uric acid level at the time of flare, it does not mean that they don’t have gout
What lab data needs to be done in the case of an acute attack?
- uric acid level needs to be drawn
- CrCl and BUN (to measure kidney fcn)
- CBC (abnormal CBC can go along with leukaemia or cancer)
What are inter-critical periods?
Periods between attacks:
- Second attack occurs within 6 months to 2 years
- With subsequent attacks inter critical periods become shorter
- Attacks become polyarticular, more severe, and longer lasting
What are some chronic complications of gout?
- Nephrolithiasis (development of uric acid stones in kidneys)
- Gouty nephropathy (chronic or acute): precipitation of uric acid in kidneys
- Tophi formation (uric acid deposits into many peripheral sites)
_____ is really used to prevent precipitation of uric acid in the kidneys
allopurinol
What is chronic tophaceous gout?
-chronic urate deposits in cartilage, tendons, synovial membranes
Common sites of chronic tophaceous gout?
- toe, fingers, wrists, ears, knees
- achilles tendon
When does chronic tophaceous gout occur?
- when inter critical periods no longer pain free (10 years of acute intermittent gout)
- the chronic accumulation of uric acid in the joint will eventually destroy the joint
50-70% of patients will develop chronic tophaceous gout if ?
hyperuicemic therapy not initiated
Treatment goals of gout attack?
- relieve pain and inflammation within 48 hours of an acute attack
- complete resolution of symptoms in 7 days
- reduce uric acid levels to below 360 umol/L
- prevent recurrent attacks of gouty arthritis
- prevent chronic complications of gout
What are some pharmacological therapy options for an acute gouty attack ?
- NSAIDs
- COX inhibitor
- colchicine
- corticosteroids
What are some pharmacological therapy for prophylaxys short term?
- colchicine 0.6 mg BID
- low dose NSAIDs
*short term for about 3-6 months
What are some pharmacological therapy for prophylaxys long term?
- allopurinol
- febuxostat
First step of treating gout attack?
resolve acute flare with anti-inflammatory agent
Second step of treating gout attack?
Initiate uric acid lowering therapy
-target levels < 6 mg/dL
*can use concomitant anti-inflammatory prophylaxis for up to 6 months to prevent mobilization flares
Third step of treating gout attack?
Control serum uric acid levels:
- continue irate-lowering therapy to control flares and avoid continual crystal deposits
- use for at least 3-6 months while serum urate levels normalize
____ diuretics can increase uric acid levels
thiazide
What drugs are capable of inducing hyperuricemia and gout?
- diuretics (esp thiazide)
- salicylates
- theophylline
- glucocorticoids
- ketoconazole
How should NSAIDs be taken in a gout attack?
- early
- at max dose
- recommend max dose at first sign of an attack
- lower dose as symptoms resolve (4-5 days)
What is the inflammatory dose of ibuprofen?
600mg QID
What is the inflammatory dose of naproxen?
750 mg then 500mg BID
NSAIDs should also be given with prescription ____ for GI protection
PPI
How long do you continue NSAID use?
until joint pain has resolved totally for at least 48 hours (could be about 7-10 days)
Any NSAID better than another?
no
What dose of colchicine do we recommend?
1.2mg followed by 0.6mg in one hour
total dose = 1.8mg
Why is lower dose of colchicine better than higher dose?
- no difference in efficacy
- less incidence in GI toxicity
*giving more colchicine does not help gout but only increases risk of GI side effects
What are some noticeable drug interactions with colchicine?
- clarithromycin
- diltiazem
- verapamil
- statins and fibrates increase myalgia
Colchicine summary for gout attacks
- start ASAP after the onset of a flare
- low dose colchicine just as effective as high dose
- patients receiving prophylaxis therapy may receive Tx dosing; wait 12 hours and resume prophylaxis
- dosage adjustments need with 3A4 inhibitors and for CrCl < 30 mL/min
Describe IA injections of corticosteroids for acute gouty arthritis
Septic arthritis needs to be ruled out first.
Single injection of:
- Methylprednisolone acetate 10-40mg
- Dexamethasone 0.8-4mg
Pain relief within 12-24 hours - lasts for duration of attack
Describe systemic corticosteroids for acute gouty arthritis
- Prednisone 20-40 mg/day x 4 days
- Taper over 1-2 weeks
- Pain relief within 12-48 hours
- Used for refractory attacks or when other agents CI
What do you need to consider before initiating prophylactic therapy?
Must consider patient:
- severity of acute attack
- response to treatment
- serum urate concentrations
- another change being made to decrease UA
Who is a candidate for short term prophylactic therapy?
-Patients with no top and normal or slightly elevated uric acid levels
What medications are used for short term prophylactic therapy?
- colchicine 0.6 mg BID
- low dose NSAIDs
When do you d/c short term prophylactic therapy?
if uric acid normal and patient is symptom-free for 6 months
Which patients need urate lowering therapy?
- recurrent attack, arthropathy, or X-ray chagnes
- tophi
- gout with chronic kidney disease
- recurring renal stones
- need for ongoing diuretic Tx (after 1st gout attack)
Goals of urate lowering therapy?
-uric acid level of <360 umol/L
MOA of allopurinol
-Blocks conversion of hypoxanthine to xanthine and xanthine to uric acid
Approved dosing of allopurinol
100mg to 800mg daily
active metabolite of allopurinol ?
oxypurinol
What is AHS (allopurinol hypersensitivity syndrome) ?
- isolated rash may occur in up to 2% of patients
- severe cutaneous reactions, fever, eosinophilia, leukocytosis, renal involvement and hepatitis
- mortality up to 25-30%
- risk factors include recent onset of therapy, chronic kidney disease, thiazides
What is the prophylactic therapy for urate lowering therapy?
2 options
1)
- Colchicine 0.6mg OD (if CrCl < 50)
- Colchicine 0.6mg BID (if CrCl > 50)
2) Low Dose NSAIDs
- Naproxen 250 mg po BID
When should allopurinol be initiated?
- 3+ weeks after resolution of acute attack
- should initiate prophylactics 2 weeks before start
What is starting dose of allopurinol?
100mg OD
(50mg OD if CrCl < 50 mL/min)
Titrate dose up by 100 mg every month until target of uric acid < 360 umol/L
Do you discontinue allopurinol during acute flares?
nope
What do you avoid combining allopurinol with?
- azathioprine
- 6-MP
*these are 2 chemo drugs that use xanthine oxidase to metabolize these drugs so this interaction results in significant toxicities
How long do you keep prophylaxis on for?
4-6 months
Can dose allopurinol beyond ___ mg/day if needed
300
List and describe 2 Uricosuric agents
Probenecid and Sulfinpyrazone
- require BID or TID dosing
- many drug interactions
- ineffective as CrCl decreases
List 2 off label uricosuric agents
- Losartan
- Fenobitrate
____ is a new urate lowering agent
Febuxostat
MOA of Febuxostat (urate lowering agent)
Febuxostat is a potent non-purine selective inhibitor of xanthine oxidase
Is Febuxostat better than Allopurinol ?
- 3 phase III clinical trials found febuxostat to be superior to allopurinol in the reduction of uric acid
- proportion of patients with gout flares was no different in 2 trials and greater for febuxostat in one trial
*problem with these 3 studies was that they maxed out at 300mg of allopurinol and if they had increased it to a higher dose it may have shown different results
What is the dosing of Febuxostat?
- Recommend initial dose of 40mg daily
- May titrate to 80mg daily after 2 weeks if serum uric acid > 360 umol/L
- No dose adjustment needed if CrCl > 30 mL/min
- Safe in mild to moderate hepatic impairment
What should you avoid Febuxostat in?
- Azathioprine
- 6-MP
Should you choose Febuxosatat or Allopurinol ?
- Both agents are effective in the reduction of uric acid (if a target to treat approach is used)
- Febuxostat appears to be tolerated in patients with AHS
- Regardless of the agent, prophylaxis with colchicine or NSAIDs (or perhaps low dose steroids) should be used for a least 6 months after initiation of urate lowering therapy
Is Febuxostat or Allopurinol cheaper?
Allopurinol
-it is also covered under pharmacare part 1 and Febuxostat is not
List some quick pearls for gout
- Uric acid levels can be normal during an acute attack - check levels 2-3 weeks later
- NSAIDs - max dose then taper and d/c 2 days after the resolution of symptoms
- Use only low-dose colchicine for acute attacks
- Have drug at home in preparation for next attack
- Start urate lowering agent 2-3 weeks post acute attack
- Start low and go slow with rate lowering therapy (ex. if using allopurinol start at 100mg and titrate up)
- Don’t forget to use prophylaxis for 6 months
- Remember to continue urate lowering therapy in acute attacks
- Vitamin C 500-1000 mg is effective in reducing UA > 10% in 2 months
- Increase diary product intake
- Spend time addressing the comorbidities of gout
Counselling tips for NSAIDs
take with food to reduce stomach upset
Counselling tips for colchicine
review dosing regimen to avoid potential toxicity
Counselling tips for steroids
review tapering regimen and supply a calender
When should pain improve in a gout attack?
pain should improve over the next 24-36 hours
Counselling tips:
Adjunctive Tx with a acetaminophen +/- _____ may be helpful initially
codeine 8 mg
Counselling tips:
Tell patient to reduce general ______ consumption
alcohol
Counselling tips:
Make sure patient has proper and comfortable ______
footwear
When should you follow up with gout patient after acute attack?
in 2-3 days to check for improvement and monitor adverse effects
Do gout patients need routine lab work?
Yes - need blood work to monitor how well the medication is working and to avoid potential adverse effects
