drugs for crystal arthropathies

Question 1

facts about gout

Answer 1

an inflammatory arthritis
common in men
associated with an incease in cardiovascular mortality

Question 2

normal upper range of uric acid

Answer 2

in men - 0.42mmol/L (saturation point)

in women - 0.36 mmol/L

Question 3

hyperuricaemia

Answer 3

levels > 0.42 mmol/L

Question 4

when uric acid is above saturation point

Answer 4

monosoodium urate crystals deposit into joint and peri articualr tissues throughout the body

Question 5

hyperuricaemia will cause gout

Answer 5

false
not everyone with increased uric acid get gout
uric acid may not be increased in acute gout
however, 80-90% of patients with gout are hyperuicaemic

Question 6

uric acid/uate is derived from

Answer 6

diet (1/3)
endogenoous liver biosynthesis (2/3)
- final product of purine metabolism (in humans)

Question 7

uric acid/urate is eliminated by

Answer 7

gut (1/3)

kidneys (2/3)

Question 8

uric acid solubility

Answer 8

is a weak organic acid - poorly soluble in acidic pH (urine) and low temperatures (why peripheraal joints are more severely effected)

Question 9

uric acid biosynthesis

Answer 9

derived from purine metabolism in the liver

Question 10

uric acid excretion

Answer 10

100% uric acid is filtered through the glomerulus
99% is reabsorbed in proximal tubule
6-10% secreted in the distal proximal tubule

Question 11

genetic component of gout

Answer 11

90% of hyperuraemics under excrete uric acid

Question 12

what is gout

Answer 12

inflammatory arthritis
chronic asymptomatic hyperuricaemia leads to supersaturation of body tissues with urate crystals
uric acid - decreased solubility in acidic and cold conditions
crystals depsit around joints, especially extremities
crystals shed into joint

Question 13

definitive diagnosis of gout

Answer 13

urate crystals in synovial fluid

Question 14

causes of gout

Answer 14

exact cause uncertain in most cases
polygenic but mostly due to decreased renal excretion of uric acid
men 3x more than women

Question 15

dietary triggers

Answer 15

obesity
increased purine intake
increased fructose
meta, seafoood, sugary drinks, beer, spirits,

Question 16

good foods for diet

Answer 16

coffee
dairy products
vit C

Question 17

other risk factors for gout

Answer 17

urate transporter mutations 
hyperrtension 
metabolic syndrome 
chronic renal failure 
drugs 
transplantation - kidney and heart

Question 18

drugs triggering gout

Answer 18

thiazide and loop diuretics (for hypertension)
low dose aspirin (causes problems with renal excretion)
cyclosporin (used to prevent transplant rejection)

Question 19

main cause of gout

Answer 19

decreased renal excretion in distal proximal tubule
increased purines in diet (alcohol, meat, seafood)
increased purine turnover (alcohol, fructose, obesty, tumour lysis)

Question 20

monosodium urate crystals building up into the tissues

Answer 20

get shed into the joints
set up inflammatory response
kinin, complement and plasmin systems
neutrophilc infiltration - engulf crystals
release of toxic oxygen metabolites
tissues lysis and release of proteolytic enzymes

Question 21

preclinical gout

Answer 21

asymptomatic hyperuricaemia

crystall deposits increase in tissues fro years then finally crystals may shed into the joint

Question 22

two clinical phases of gout

Answer 22

intermittent acute gout - s symptoms of gout or signs of tophi between attacks
chronic tophaceous gout - if raised uric acid not adequately treated

Question 23

acute gout

Answer 23

intermittanet pauci-articular inflammatory arthritis
sudden onset
red and intensely painful
extensive swelling
50% first attacks occur in 1st metatarsophalangeal joint (podagra)

Question 24

acute gout is assciated with

Answer 24

fever
can be poly articular (especially in eldery and women)
self limiting

Question 25

chronic gout

Answer 25

recurrent attacks + inadequate urate lowering treatment leads to chronic toophaceous gout erosion of neighbouring joints - deformity and restricted movement

Question 26

tophi are

Answer 26

large crystal deposits oon the extensor surfaces (fingers/hands, elbows, tendons, ear)

Question 27

chronic gout can lead to

Answer 27

nephrolithiasis and renal tissue depsits - chronic renall faillure contributes to cardioovascular disease and stroke

Question 28

podagra

Answer 28

sudden onset gout in the first metatarsophalangeal joint

Question 29

treatment approach for chronic gout

Answer 29

much earlier use of urate-lwering therapies to treat underlying disease

Question 30

treatment of acute gout - pain relief

Answer 30

pain relief - NSAIDs - colchicine - glucocorticoids - oral and intra-articular (not if septic arthritis)

Question 31

treatment of acute gout - urate lowering therapy

Answer 31

maintain ULT if previously diagnosed gout | start urate lowering therapy if new diagnosis - lowest dose and increase dose very slowly

Question 32

colchicine

Answer 32

alkaloid product of autumn crocus - ancient remedy mechanism of action not fully understood but binds tubulin - stops microtubule assembly to reduce - cell division - neutrophil motility - chemokine production inflammatory cell recruitment stops

Question 33

colchicine is absorbed

Answer 33

rapidly orally

Question 34

why isnt colchicine given as a first line therapy

Answer 34

vomiting and diarrhoea - very common first sign of toxicity | muscle damage, myelosuppression, multple organ failure and there is no antidote

Question 35

do not prescribe colchicine if

Answer 35

kidney or liver function is poor | watch for DDIs

Question 36

how long does acute gout last

Answer 36

two week

Question 37

aim of treating chronic gout

Answer 37

long term decrease in uric acid | lifestyle - diet, alcohol, and weight loss

Question 38

3 main drug group for chroonic gout

Answer 38

xanthine oxidase inhibitors uricosuric agents uricase agents start during acute attack - better capture and compliance

Question 39

main xanthine oxidase inhibitor

Answer 39

allopurinol

Question 40

allopurinol

Answer 40

xanthine oxidase inhibitor hypoxanthine analogue competitively inhibits XO to decrease uric acid production XO also converts allopurinol to alloxanthine/oxypurinol alloxanthine non competitively inhibits XO pharmacological action is largely alloxanthine

Question 41

drug of choice for long term treatment of gout

Answer 41

allopurinol

Question 42

prescribing allopurinol

Answer 42

well absorbed orally single daily dose renally excreted decrease dose and titrate more slowly in RF

Question 43

why start low, go slow

Answer 43

dose esclaltion strategy | decreases risk of acute flare

Question 44

aims of long term urate lowering therapy

Answer 44

decrease urc acid concentration to <0.36 mmol/L disolve tophi, calculi and urate crystals in other tissues maintain dose when SUA reaches 0.36

Question 45

preventing of acute gout flare treatment during SUA

Answer 45

prophylactic NSAIDs or cochicine

Question 46

adverse effects of allopurinol

Answer 46

mostly GI | allopurinol hypersensitivity syndrome - drug reaction, rash with eosinophilia and systemic symptoms

Question 47

alloopurinol hypersensitivity syndrome

Answer 47

if rash i severe - stevens-johnson syndrome - rare but potentially fatall risk increased if starting dose is high east asian patients at higher risk consider testing patients (PCR)

Question 48

dangerous drug interactions with allopurinol

Answer 48

mercaptopurne and azathioprine purine analogues metabolised by XO allopurinol increases their effects by blocking XO affects fast replicating tissues, myelosuppression, diarrhoea, life threateneing

Question 49

feboxostat

Answer 49

``` non purine selective inhibitor of XO not a purine analogue metabolised mainly in theliver useful in pateints with renal failure or those who cannot tolerate allopurinol much more expensive than allopurinol ```

Question 50

uricosuric agents

Answer 50

blocks urate re uptake in proximal tubule | useful for under excreters

Question 51

uricase agents

Answer 51

rasburicase and pegloticase dervides from aspergillus fluvus catalyses conversion of uric acid to allantion rapidly decreases serum uric acid levels IV only short half life single use in tumour lysis syndromes