Gout Flashcards
Define the gout ..
It is metabolic disease in which plasma urate level is raised
Causes of gout:
Overproduction of uric acid (20%)
Reduced renal excretion of uric acid (80%)
E.g of overproduction of uric acid:
Excessive cell destruction (lymphoproliferative disorders) especially during their treatment
Or inherited defects that increase purine synthesis.
E.g of reduced renal excretion:
Renal failure
Drugs, e.g most diuretics, low dose aspirin
Lactate that formed from alcohol can reduce the tubular secretion of uric acid
Hyperuricemia can lead to deposition of sodium urate crystals in tissues, especially :
Joints and kidney
Characteristics of gout:
Chatacterized by recurrent episodes of acute arthritis and formation of uric acid calculi in the kidneys
Gout causes acute arthritis due to:
Deposits of monosodium urate in joints and cartilage
Drug used to treat gout may act in the following ways:
By inhibiting uric acid synthesis
Increasing uric acid excretion
Inhibiting leukocyte migration into the joint
By a general anti-inflammatory and analgesic effect (NSAIDs).
Drugs that inhibit uric acid synthesis :
Allopurinol
The main prophylactic drug for gout:
Allopurinol
Drugs that increase uric acid excretion
uricosuric agents: probenecid and sulfinpyrazone
Drug that inhibits leukocyte migration into the joint:
Colchicine
Causes of acute gout:
Excessive alcohol consumption, a diet rich in purines, or kidney disease
Drugs used in acute gout:
NSAIDs
Glucocorticoids
Colchicine
Causes of chronic gout:
Genetic defect that increase the rate of purine synthesis
Renal deficiency
Excessive production of uric acid associated with cancer chemotherapy
Drugs used in chronic gout :
Uricosuric drugs: probencid, sulfinpyrazone
Allopurinol
Cholchicine
Plant alkaloid used for treatment of acute and chronic gout:
Colchicine
Mechanism of action of colchicine:
It bind to tubulin causing its depolymerization, thus decreasing migration of granulocytes into the effected area
It blocks cell division by binding to mitotic spindles
It also inhibits the synthesis and release of the leukotrients
Pharmacokinetic of colchicine
It is administered orally
It is recycled in the bile and is excreted unchanged in the feces or urine
Colchicine using should be avoided in :
in patients with a creatinine clearance of less than 50 mL/min.
Adverse effects of colchicine:
nausea, vomiting, abdominal pain and diarrhea
Chronic administration may lead to myopathy, neutropenia, aplastic anemia and alopecia.
Contraindication of colchicine:
Should not be used in pregnancy.
Should be used with caution in patients with hepatic, renal or cardiovascular disease.
Purine analog reduces the production of uric acid by competitive inhibition:
Allopurinol
Mechanism of action of Allopurinol:
It reduces the production of uric acid by competitively inhibiting the last two steps in uric acid biosynthesis that are catalyzed by xanthine oxidase
xanthine and hypxanthine are less dangerous than uric acid:
This circulating purine derivatives are more soluble and, therefore, are less likely to precipitate
Therapeutic uses of allopurinol:
It is effective i treatment of primary hyperuricemia of gout and hyperuricemia secondary to other conditions
In renal disease this agent is the DOC in those with a history of kidney stones or renal function impairment.
Pharmacokinetics of Allopurinol :
It is completely absorbed after oral administration
The primary metabolite is alloxanthine (oxypurinol), which is also a xanthine oxidase inhibitor with a half-life of 15 to 18 hours
The half-life of allopurinol is 2 hours
Effective inhibition of xanthine oxidase can be maintained with once-daily dosage.
True
Adverse effects of Allopurine:
It is well tolerated by most patients.
Hypersensitivity reactions.
nausea and diarrhea are common
Acute attacks of gout may occur more frequently during the first several weeks of therapy
Colchicine or NSAIDs should be administered with Allopurinol concurrently :
Because acute attacks of gout may occur more frequently during the first several weeks of therapy.
Drug interaction of Allopurinol :
It interferes with the metabolism of the anticancer agent 6-mercaptopurine and the immunosuppressant azathioprine, requiring a reduction in dosage of these drugs.
Weak organic acids that promote renal clearance of uric acid:
Uricosuric agents :Probenecid and sulfinpyrazone.
Mechanism of action of uricosuric drugs:
They inhitbit the urate-anion exchanger in the proximal tubule that mediates urate reabsorption.
Drug interaction of uricosurics
Probenicid decreases tubular secretion of some drugs:
Peniccillin, thiazide and loop diuretics
It also inhibits excretion of naproxen, ketoprofen and indomethacin.
Side effects of uricosurics:
Formation of renal urate stones
Allergy
GIT disturbances
Aspirin antagonize uricosurics (in low dose)
N.B about uricosurics:
In patients secreting large amount of uric acid in urin, avoid uricosurics.
NSAIDs im Gout:
They work to reduce swelling in a joint and include ibuprofen, naproxen, indomethacin and celecoxib.
NSAIDs in low dose:
They inhibit excretion of uric acid by competing with uric acid transport causing gouty attack
NSAIDs in high dose:
They induce renal excretion of uric acid by preventing reabsorption of uric acid
Glucocorticoids in Gout:
They decrease the pain, swelling, redness and warmth (inflammation) of gout.
Corticosteroids may be used for :
Gout attacks that are limiting to a single joint.
Gout attacks that do not respond to NSAIDs or colchicine
Corticosteroids should not be given to people who have a joimt infection ….why?
Because it has immunosupressant effect
If only one joints is affected:
If multiple joints are involved:
injection of corticosteroids into the joint may be most effective.
Corticosteroids may be injected into a vein or muscle or taken by mouth in pill form, in gradually decreasing doses.
Corticosteroid and blood pressure
People who have high blood pressure should monitor their pressure while they are using corticosteroids.
Corticosteroids and diabetes
People who have diabetes may need more medicine or insulin when they are using corticosteroids to treat their gout
Corticosteroids are usually prescribed only for a short time :
Because of their potential side effects if used for a long time.
The power of Corticosteroid to relieve pain
Corticosteroids usually provide rapid relief from from gout symptoms.
Mechanism of action of Pegloticase:
It works by breaking down urate into allantoin( more soluble than uric acid), an end-product that is more easily excreted.
Pharmacokinetics of Pegloticase:
It is given by repeated I.V infusions and can lower urate levels rapidly and profoundly.
Adverse effects of pegloticase:
It may causes allergic-like infusion reactions, some of which can be severe (so needs careful monitoring).
Pegloticase is effective in the long term in only about 50% of cases:
It is recommended to be used in patients with advanced gout that cannot be controlled with oral urate-lowering therapies
Urate transporter inhibitor that was initially approved in late 2015
Lesinurad
Lesinurad should not be used alone:
It is given in addition to allopurinol if the person’s uric acid levels are still too high.
