Podcast
Questions and Answers
What is the primary cause of primary gout in 90% of cases?
What is the primary cause of primary gout in 90% of cases?
- Increased uric acid production
- Dietary factors
- Genetic predisposition
- Decreased uric acid excretion (correct)
Which enzyme is responsible for purine metabolism leading to uric acid production?
Which enzyme is responsible for purine metabolism leading to uric acid production?
- Adenine deaminase
- Hypoxanthine guanine phosphoribosyltransferase
- Uricase
- Xanthine oxidase (correct)
What renal process is enhanced to promote uric acid excretion?
What renal process is enhanced to promote uric acid excretion?
- Increased blood flow to kidneys
- Decreased tubular reabsorption
- Alkalization of urine (correct)
- Renal filtration rate
Which of the following drugs is known to decrease uric acid excretion?
Which of the following drugs is known to decrease uric acid excretion?
What is the major dietary factor associated with increased uric acid production?
What is the major dietary factor associated with increased uric acid production?
What term describes the syndrome related to tissue breakdown during treatment of hematologic malignancies?
What term describes the syndrome related to tissue breakdown during treatment of hematologic malignancies?
What triggers the precipitation of monosodium urate crystals in joint tissue?
What triggers the precipitation of monosodium urate crystals in joint tissue?
Which of the following conditions is an example of a mixed cause of hyperuricemia?
Which of the following conditions is an example of a mixed cause of hyperuricemia?
What is the primary reason colchicine is not a first-choice treatment for acute gouty arthritis?
What is the primary reason colchicine is not a first-choice treatment for acute gouty arthritis?
Which of the following are characteristics of Familial Mediterranean Fever (FMF)?
Which of the following are characteristics of Familial Mediterranean Fever (FMF)?
What is a recognized adverse effect of high oral doses of colchicine?
What is a recognized adverse effect of high oral doses of colchicine?
Which NSAIDs are FDA approved specifically for the treatment of acute gouty arthritis?
Which NSAIDs are FDA approved specifically for the treatment of acute gouty arthritis?
What should be done to the dosage of NSAIDs when taken concurrently with probenecid?
What should be done to the dosage of NSAIDs when taken concurrently with probenecid?
Which of the following best describes the onset of action of colchicine compared to NSAIDs?
Which of the following best describes the onset of action of colchicine compared to NSAIDs?
Among the adverse effects of colchicine, which is classified as the most severe?
Among the adverse effects of colchicine, which is classified as the most severe?
What is the recommended initial oral dose of colchicine for an acute gout attack?
What is the recommended initial oral dose of colchicine for an acute gout attack?
What is the primary mechanism of action of probenecid when used in small doses?
What is the primary mechanism of action of probenecid when used in small doses?
What occurs when probenecid is administered in large doses?
What occurs when probenecid is administered in large doses?
What is the recommended timing for the use of uricosuric drugs like probenecid in relation to an acute gout attack?
What is the recommended timing for the use of uricosuric drugs like probenecid in relation to an acute gout attack?
Which of the following is a potential adverse effect of probenecid?
Which of the following is a potential adverse effect of probenecid?
How does the use of probenecid during an acute gout attack affect inflammation?
How does the use of probenecid during an acute gout attack affect inflammation?
What is the primary therapeutic use of probenecid?
What is the primary therapeutic use of probenecid?
What role do leukocytes play in the inflammation process of gout?
What role do leukocytes play in the inflammation process of gout?
Why might probenecid not be suitable for treating acute gout attacks?
Why might probenecid not be suitable for treating acute gout attacks?
What is the mechanism of action of allopurinol in treating gout?
What is the mechanism of action of allopurinol in treating gout?
What is the target uric acid level for effective gout treatment with allopurinol?
What is the target uric acid level for effective gout treatment with allopurinol?
What is a common adverse effect of allopurinol therapy?
What is a common adverse effect of allopurinol therapy?
Which medication should not be administered during an acute gout attack?
Which medication should not be administered during an acute gout attack?
What condition is peglioticase especially indicated for?
What condition is peglioticase especially indicated for?
What effect does colchicine have on leukocytes?
What effect does colchicine have on leukocytes?
Which enzyme does pergloticase replace to enhance uric acid metabolism?
Which enzyme does pergloticase replace to enhance uric acid metabolism?
Co-administration of allopurinol with which of the following drugs may lead to increased toxicity?
Co-administration of allopurinol with which of the following drugs may lead to increased toxicity?
Chronic hyperuricemia is defined as having uric acid levels greater than $7 mg/dl$.
Chronic hyperuricemia is defined as having uric acid levels greater than $7 mg/dl$.
The renal excretion of uric acid is decreased by the alkalization of urine.
The renal excretion of uric acid is decreased by the alkalization of urine.
Monosodium urate crystals precipitate when serum uric acid levels decrease.
Monosodium urate crystals precipitate when serum uric acid levels decrease.
Diuretics are among the drugs that can increase uric acid retention in the body.
Diuretics are among the drugs that can increase uric acid retention in the body.
Decreased uric acid excretion accounts for approximately 90% of primary gout cases.
Decreased uric acid excretion accounts for approximately 90% of primary gout cases.
A high protein diet decreases production of uric acid in the body.
A high protein diet decreases production of uric acid in the body.
Tumor lysis syndrome is associated with decreased uric acid production during treatment of hematologic malignancies.
Tumor lysis syndrome is associated with decreased uric acid production during treatment of hematologic malignancies.
Gout is classified as an autoimmune disorder.
Gout is classified as an autoimmune disorder.
Uric acid crystals cause swelling and inflammation of the joint tissue.
Uric acid crystals cause swelling and inflammation of the joint tissue.
Probenecid has a monophasic mechanism of action regardless of dosage.
Probenecid has a monophasic mechanism of action regardless of dosage.
Leukocytes contribute to inflammation during an acute gout attack by releasing proteolytic enzymes.
Leukocytes contribute to inflammation during an acute gout attack by releasing proteolytic enzymes.
Probenecid should be given immediately during an acute gout attack to prevent inflammation.
Probenecid should be given immediately during an acute gout attack to prevent inflammation.
High doses of probenecid can lead to a decrease in uric acid excretion.
High doses of probenecid can lead to a decrease in uric acid excretion.
Probenecid is effective as a treatment for acute gout attacks.
Probenecid is effective as a treatment for acute gout attacks.
Adverse effects of probenecid include interstitial nephritis and aplastic anemia.
Adverse effects of probenecid include interstitial nephritis and aplastic anemia.
The therapeutic use of probenecid includes prolonging the half-life of some acidic drugs.
The therapeutic use of probenecid includes prolonging the half-life of some acidic drugs.
Colchicine provides relief from pain within 1-3 hours after oral administration.
Colchicine provides relief from pain within 1-3 hours after oral administration.
Familial Mediterranean Fever (FMF) typically presents by the second decade of life.
Familial Mediterranean Fever (FMF) typically presents by the second decade of life.
Diarrhea is considered one of the rare side effects of high oral doses of colchicine.
Diarrhea is considered one of the rare side effects of high oral doses of colchicine.
Indomethacin and naproxen are not FDA approved for acute gouty arthritis.
Indomethacin and naproxen are not FDA approved for acute gouty arthritis.
Corticosteroids are used only when colchicine and NSAIDs are sufficient to control acute attacks.
Corticosteroids are used only when colchicine and NSAIDs are sufficient to control acute attacks.
Allopurinol is a potent inhibitor of xanthine oxidase and has a long duration of action.
Allopurinol is a potent inhibitor of xanthine oxidase and has a long duration of action.
Probenecid enhances the renal excretion of NSAIDs.
Probenecid enhances the renal excretion of NSAIDs.
The most serious adverse effects of colchicine include aplastic anemia and agranulocytosis.
The most serious adverse effects of colchicine include aplastic anemia and agranulocytosis.
The recommended starting dose of allopurinol for gout treatment is 300 mg once daily.
The recommended starting dose of allopurinol for gout treatment is 300 mg once daily.
Colchicine can inhibit neutrophil motility, making it useful for treating gout attacks.
Colchicine can inhibit neutrophil motility, making it useful for treating gout attacks.
Attacks of Familial Mediterranean Fever (FMF) typically last between 3-5 days.
Attacks of Familial Mediterranean Fever (FMF) typically last between 3-5 days.
Pegloticase is indicated for mild gout cases that respond to standard treatments.
Pegloticase is indicated for mild gout cases that respond to standard treatments.
Allopurinol can lead to the precipitation of acute gout at the start of therapy due to mobilization of uric acid crystals.
Allopurinol can lead to the precipitation of acute gout at the start of therapy due to mobilization of uric acid crystals.
Aspirin is known to enhance uric acid excretion and support probenecid effects.
Aspirin is known to enhance uric acid excretion and support probenecid effects.
Mercaptopurine and theophylline levels can increase dramatically when taken with allopurinol.
Mercaptopurine and theophylline levels can increase dramatically when taken with allopurinol.
Colchicine is a synthetic drug used primarily to treat rheumatoid arthritis.
Colchicine is a synthetic drug used primarily to treat rheumatoid arthritis.
What pathological event initiates gouty arthritis when serum uric acid increases?
What pathological event initiates gouty arthritis when serum uric acid increases?
Explain how alkalization of urine affects uric acid excretion.
Explain how alkalization of urine affects uric acid excretion.
Identify two factors that lead to decreased uric acid excretion.
Identify two factors that lead to decreased uric acid excretion.
What are the major dietary factors influencing increased uric acid production?
What are the major dietary factors influencing increased uric acid production?
Describe how diuretics contribute to the retention of uric acid.
Describe how diuretics contribute to the retention of uric acid.
How is the majority of body uric acid eliminated?
How is the majority of body uric acid eliminated?
What is the relationship between tissue breakdown and uric acid production during leukemia treatment?
What is the relationship between tissue breakdown and uric acid production during leukemia treatment?
What kind of syndrome is associated with sex-linked uric aciduria?
What kind of syndrome is associated with sex-linked uric aciduria?
What biphasic action does probenecid exhibit at small doses?
What biphasic action does probenecid exhibit at small doses?
Explain the risk associated with administering probenecid during an acute gout attack.
Explain the risk associated with administering probenecid during an acute gout attack.
How do leukocytes contribute to the inflammation seen in gout?
How do leukocytes contribute to the inflammation seen in gout?
What is a key therapeutic use of probenecid regarding other acidic drugs?
What is a key therapeutic use of probenecid regarding other acidic drugs?
Describe the consequences of probenecid when given in large doses.
Describe the consequences of probenecid when given in large doses.
What are the observed adverse effects when taking probenecid?
What are the observed adverse effects when taking probenecid?
Why is it recommended to wait 2-3 weeks after an acute attack to use probenecid?
Why is it recommended to wait 2-3 weeks after an acute attack to use probenecid?
What inflammatory mediators are released by leukocytes during the gout inflammation process?
What inflammatory mediators are released by leukocytes during the gout inflammation process?
What condition is indicated for the lifelong use of allopurinol?
What condition is indicated for the lifelong use of allopurinol?
How does allopurinol's mechanism of action affect uric acid levels?
How does allopurinol's mechanism of action affect uric acid levels?
What is the main reason to administer NSAIDs or colchicine when starting allopurinol therapy?
What is the main reason to administer NSAIDs or colchicine when starting allopurinol therapy?
What adverse effect is commonly associated with allopurinol treatment?
What adverse effect is commonly associated with allopurinol treatment?
What is the dosing adjustment protocol for allopurinol when treating gout?
What is the dosing adjustment protocol for allopurinol when treating gout?
Which agent is used in severe gout cases unresponsive to other treatments?
Which agent is used in severe gout cases unresponsive to other treatments?
What is the mechanism of action of colchicine in managing gout?
What is the mechanism of action of colchicine in managing gout?
Which drugs should be closely monitored when coadministered with allopurinol?
Which drugs should be closely monitored when coadministered with allopurinol?
What are the typical duration and features of attacks in Familial Mediterranean Fever (FMF)?
What are the typical duration and features of attacks in Familial Mediterranean Fever (FMF)?
What is the main reason colchicine is considered a second-line treatment for acute gouty arthritis?
What is the main reason colchicine is considered a second-line treatment for acute gouty arthritis?
Describe the primary mechanism by which high oral doses of colchicine can lead to diarrhea.
Describe the primary mechanism by which high oral doses of colchicine can lead to diarrhea.
What dosage adjustment should be made for NSAIDs when they are taken with probenecid?
What dosage adjustment should be made for NSAIDs when they are taken with probenecid?
What characterizes the adverse effects of colchicine, specifically in terms of severity?
What characterizes the adverse effects of colchicine, specifically in terms of severity?
What is the recommended initial oral dose of colchicine for managing an acute gout attack?
What is the recommended initial oral dose of colchicine for managing an acute gout attack?
How do indomethacin and naproxen compare to colchicine in terms of onset for relieving acute gout attacks?
How do indomethacin and naproxen compare to colchicine in terms of onset for relieving acute gout attacks?
What condition does the atypical presentation of recurrent polyserositis suggest?
What condition does the atypical presentation of recurrent polyserositis suggest?
Gout is a form of inflammatory arthritis due to deposition of monosodium urate crystals in the ______ tissue.
Gout is a form of inflammatory arthritis due to deposition of monosodium urate crystals in the ______ tissue.
Chronic hyperuricemia is defined as having uric acid levels greater than ______ mg/dl.
Chronic hyperuricemia is defined as having uric acid levels greater than ______ mg/dl.
The renal excretion of uric acid is enhanced by ______ of urine.
The renal excretion of uric acid is enhanced by ______ of urine.
Decreased uric acid excretion accounts for approximately ______% of primary gout cases.
Decreased uric acid excretion accounts for approximately ______% of primary gout cases.
High protein diets can lead to ______ uric acid production.
High protein diets can lead to ______ uric acid production.
Monosodium urate crystals are selectively precipitated around the joint tissue when serum uric acid levels ______.
Monosodium urate crystals are selectively precipitated around the joint tissue when serum uric acid levels ______.
Some drugs, such as ______, may interfere with the excretion of uric acid, leading to its retention.
Some drugs, such as ______, may interfere with the excretion of uric acid, leading to its retention.
Alcohol consumption is considered a ______ cause of hyperuricemia.
Alcohol consumption is considered a ______ cause of hyperuricemia.
Uric acid crystals cause swelling and inflammation of the ______ tissue.
Uric acid crystals cause swelling and inflammation of the ______ tissue.
Leukocytes eventually die with the release of ______ enzymes and inflammatory mediators.
Leukocytes eventually die with the release of ______ enzymes and inflammatory mediators.
Probenecid inhibits tubular reabsorption of uric acid by acting on the ______ transporter.
Probenecid inhibits tubular reabsorption of uric acid by acting on the ______ transporter.
During an acute attack, rapid lowering of serum uric acid can aggravate the acute ______.
During an acute attack, rapid lowering of serum uric acid can aggravate the acute ______.
Probenecid is used as a ______ agent in chronic gout.
Probenecid is used as a ______ agent in chronic gout.
High doses of probenecid can lead to increased ______ of uric acid.
High doses of probenecid can lead to increased ______ of uric acid.
Uricosuric drugs should not be used during the acute attack but rather ______ weeks after.
Uricosuric drugs should not be used during the acute attack but rather ______ weeks after.
Adverse effects of probenecid include gastric irritation and ______ rash.
Adverse effects of probenecid include gastric irritation and ______ rash.
Colchicine provides relief from pain and reduction of inflammation after ______ hours of oral administration.
Colchicine provides relief from pain and reduction of inflammation after ______ hours of oral administration.
Familial Mediterranean Fever (FMF) is characterized by recurrent episodes of abdominal pain, pleurisy, and ______.
Familial Mediterranean Fever (FMF) is characterized by recurrent episodes of abdominal pain, pleurisy, and ______.
Common adverse effects of high oral doses of colchicine include diarrhea, alopecia, and ______.
Common adverse effects of high oral doses of colchicine include diarrhea, alopecia, and ______.
NSAIDs such as ______ and naproxen are FDA approved for the treatment of acute gouty arthritis.
NSAIDs such as ______ and naproxen are FDA approved for the treatment of acute gouty arthritis.
The recommended dose of colchicine for an acute gout attack starts with ______ mg.
The recommended dose of colchicine for an acute gout attack starts with ______ mg.
If taken with probenecid, the dose of NSAIDs must be ______ due to renal excretion inhibition.
If taken with probenecid, the dose of NSAIDs must be ______ due to renal excretion inhibition.
A serious adverse effect of colchicine includes ______ anemia, which affects bone marrow function.
A serious adverse effect of colchicine includes ______ anemia, which affects bone marrow function.
Familial Mediterranean Fever (FMF) is inherited in an ______ fashion.
Familial Mediterranean Fever (FMF) is inherited in an ______ fashion.
Allopurinol inhibits the enzyme ______ oxidase to reduce uric acid synthesis.
Allopurinol inhibits the enzyme ______ oxidase to reduce uric acid synthesis.
Pegloticase converts uric acid into the water-soluble ______.
Pegloticase converts uric acid into the water-soluble ______.
Colchicine is known for its action as a ______ blocker.
Colchicine is known for its action as a ______ blocker.
Patients with Lesch-Nyhan syndrome require allopurinol for ______.
Patients with Lesch-Nyhan syndrome require allopurinol for ______.
During acute gout attacks, colchicine inhibits the release of ______ by leukocytes.
During acute gout attacks, colchicine inhibits the release of ______ by leukocytes.
Starting dose of allopurinol for gout treatment is typically ______ mg once daily.
Starting dose of allopurinol for gout treatment is typically ______ mg once daily.
The adverse effect of allopurinol includes gastric irritation and ______ reactions.
The adverse effect of allopurinol includes gastric irritation and ______ reactions.
Allopurinol should not be given during an acute ______ attack.
Allopurinol should not be given during an acute ______ attack.
Match the following drugs with their effect on uric acid levels:
Match the following drugs with their effect on uric acid levels:
Match the following conditions with their relationship to hyperuricemia:
Match the following conditions with their relationship to hyperuricemia:
Match the following terms with their definitions related to gout:
Match the following terms with their definitions related to gout:
Match the following dietary factors with their effect on uric acid:
Match the following dietary factors with their effect on uric acid:
Match the following symptoms with their related processes in gout:
Match the following symptoms with their related processes in gout:
Match the following mechanisms with their descriptions:
Match the following mechanisms with their descriptions:
Match the following treatment strategies with their intended outcomes:
Match the following treatment strategies with their intended outcomes:
Match the following medications with their respective primary therapeutic uses:
Match the following medications with their respective primary therapeutic uses:
Match the following etiologies with their respective gout types:
Match the following etiologies with their respective gout types:
Match the following drugs with their mechanisms of action:
Match the following drugs with their mechanisms of action:
Match the following adverse effects with their corresponding medications:
Match the following adverse effects with their corresponding medications:
Match the following scenarios with the appropriate medication recommendations:
Match the following scenarios with the appropriate medication recommendations:
Match the following conditions with the medications indicated for treatment:
Match the following conditions with the medications indicated for treatment:
Match the following drug interactions with the relevant medication:
Match the following drug interactions with the relevant medication:
Match the following drug classes with their effects on uric acid levels:
Match the following drug classes with their effects on uric acid levels:
Match the following patient scenarios with the appropriate medication guidance:
Match the following patient scenarios with the appropriate medication guidance:
Match the following medications with their primary characteristics:
Match the following medications with their primary characteristics:
Match the following drug classes with their primary mechanisms of action:
Match the following drug classes with their primary mechanisms of action:
Match the following adverse effects with the respective drugs:
Match the following adverse effects with the respective drugs:
Match the following symptoms with their associated conditions:
Match the following symptoms with their associated conditions:
Match the following characteristics to their respective medications:
Match the following characteristics to their respective medications:
Match the following therapeutic uses with the appropriate drug:
Match the following therapeutic uses with the appropriate drug:
Match the following conditions with their respective mechanisms:
Match the following conditions with their respective mechanisms:
Match the following features with their descriptions:
Match the following features with their descriptions:
Match the following mechanisms with their corresponding drug actions:
Match the following mechanisms with their corresponding drug actions:
Match the following conditions with their treatments:
Match the following conditions with their treatments:
Match the following doses with their indications:
Match the following doses with their indications:
Match the following precautions with the appropriate drug:
Match the following precautions with the appropriate drug:
Match the following types of excretion alteration with their drugs:
Match the following types of excretion alteration with their drugs:
Match the following adverse effects to their corresponding medications:
Match the following adverse effects to their corresponding medications:
Match the following clinical features to their related medications:
Match the following clinical features to their related medications:
Match the following inflammatory mediators with their effects in gout:
Match the following inflammatory mediators with their effects in gout:
Study Notes
Basic Information on Gout
- Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joint tissue.
- Chronic hyperuricemia, defined as uric acid levels > 7 mg/dL (0.42 mmol/L), is the primary cause.
- Uric acid is the end product of purine metabolism, mainly excreted by the renal proximal convoluted tubule (PCT).
- Certain drugs, such as diuretics, can interfere with uric acid excretion, causing retention.
Causes of Hyperuricemia
- Decreased uric acid excretion accounts for 90% of primary gout cases, often due to:
- Medications (e.g., diuretics, aspirin).
- Kidney diseases.
- Increased uric acid production can result from:
- High-protein diets.
- Treatment of hematologic malignancies, causing tissue breakdown (tumor lysis syndrome).
- Alcohol consumption also contributes as a mixed cause.
Pathogenesis of Gouty Arthritis
- Elevated serum uric acid levels lead to the precipitation of urate crystals in joints, resulting in irritation and inflammation.
- Polymorphonuclear leukocytes (PMNs) and macrophages phagocytize uric acid crystals, causing swelling and inflammation.
- Leukocyte death releases proteolytic enzymes and inflammatory mediators (e.g., LTB4, IL-1), intensifying inflammation.
Uricosuric Drugs: Probenecid
- Probenecid has a biphasic action:
- In small doses, it inhibits tubular secretion of organic acids (including uric acid).
- In larger doses (≥500 mg twice/day), it inhibits tubular reabsorption of uric acid, enhancing its excretion.
- Therapeutic uses include treatment of chronic gout and prolonging the half-life of certain acidic drugs.
- Adverse effects may include gastric irritation, skin rash, and, rarely, interstitial nephritis or aplastic anemia.
- Should not be used during acute gout attacks as it may aggravate inflammation.
Inhibitors of Uric Acid Synthesis: Allopurinol
- Allopurinol is a synthetic purine analogue that inhibits xanthine oxidase, reducing uric acid synthesis.
- It has a long duration of action due to potent inhibition by both the drug and its metabolite.
- Recommended for patients with recurrent gout attacks, targeting uric acid levels of 5 mg/dL (0.3 mmol/L).
- May also be used in hematologic malignancies to prevent hyperuricemia.
- Common adverse effects include gastric irritation and hypersensitivity reactions; can precipitate acute gout at therapy onset.
Increase Uric Acid Metabolism: Pegloticase
- Pegloticase is a recombinant form of porcine uricase, converting uric acid to the soluble allantoin.
- Administered intravenously (8 mg every 2 weeks), it quickly lowers serum uric acid.
- Indicated for severe gout cases resistant to other treatments.
Anti-Inflammatory Drugs: Colchicine
- Colchicine is a plant alkaloid that inhibits leukocyte motility, phagocytosis, and mitosis.
- Mainly used for acute gout attacks; slower onset compared to NSAIDs, with pain relief occurring within 12–24 hours.
- High doses can lead to gastrointestinal toxicity, especially diarrhea.
NSAIDs: Indomethacin and Naproxen
- Indomethacin and naproxen are FDA-approved NSAIDs for acute gout, providing faster relief than colchicine.
- Dosage adjustments may be needed when co-administered with probenecid, which inhibits renal excretion.
Corticosteroids
- Used as anti-inflammatory agents when colchicine and NSAIDs are insufficient or contraindicated for acute attacks.
Basic Information on Gout
- Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joint tissue.
- Chronic hyperuricemia, defined as uric acid levels > 7 mg/dL (0.42 mmol/L), is the primary cause.
- Uric acid is the end product of purine metabolism, mainly excreted by the renal proximal convoluted tubule (PCT).
- Certain drugs, such as diuretics, can interfere with uric acid excretion, causing retention.
Causes of Hyperuricemia
- Decreased uric acid excretion accounts for 90% of primary gout cases, often due to:
- Medications (e.g., diuretics, aspirin).
- Kidney diseases.
- Increased uric acid production can result from:
- High-protein diets.
- Treatment of hematologic malignancies, causing tissue breakdown (tumor lysis syndrome).
- Alcohol consumption also contributes as a mixed cause.
Pathogenesis of Gouty Arthritis
- Elevated serum uric acid levels lead to the precipitation of urate crystals in joints, resulting in irritation and inflammation.
- Polymorphonuclear leukocytes (PMNs) and macrophages phagocytize uric acid crystals, causing swelling and inflammation.
- Leukocyte death releases proteolytic enzymes and inflammatory mediators (e.g., LTB4, IL-1), intensifying inflammation.
Uricosuric Drugs: Probenecid
- Probenecid has a biphasic action:
- In small doses, it inhibits tubular secretion of organic acids (including uric acid).
- In larger doses (≥500 mg twice/day), it inhibits tubular reabsorption of uric acid, enhancing its excretion.
- Therapeutic uses include treatment of chronic gout and prolonging the half-life of certain acidic drugs.
- Adverse effects may include gastric irritation, skin rash, and, rarely, interstitial nephritis or aplastic anemia.
- Should not be used during acute gout attacks as it may aggravate inflammation.
Inhibitors of Uric Acid Synthesis: Allopurinol
- Allopurinol is a synthetic purine analogue that inhibits xanthine oxidase, reducing uric acid synthesis.
- It has a long duration of action due to potent inhibition by both the drug and its metabolite.
- Recommended for patients with recurrent gout attacks, targeting uric acid levels of 5 mg/dL (0.3 mmol/L).
- May also be used in hematologic malignancies to prevent hyperuricemia.
- Common adverse effects include gastric irritation and hypersensitivity reactions; can precipitate acute gout at therapy onset.
Increase Uric Acid Metabolism: Pegloticase
- Pegloticase is a recombinant form of porcine uricase, converting uric acid to the soluble allantoin.
- Administered intravenously (8 mg every 2 weeks), it quickly lowers serum uric acid.
- Indicated for severe gout cases resistant to other treatments.
Anti-Inflammatory Drugs: Colchicine
- Colchicine is a plant alkaloid that inhibits leukocyte motility, phagocytosis, and mitosis.
- Mainly used for acute gout attacks; slower onset compared to NSAIDs, with pain relief occurring within 12–24 hours.
- High doses can lead to gastrointestinal toxicity, especially diarrhea.
NSAIDs: Indomethacin and Naproxen
- Indomethacin and naproxen are FDA-approved NSAIDs for acute gout, providing faster relief than colchicine.
- Dosage adjustments may be needed when co-administered with probenecid, which inhibits renal excretion.
Corticosteroids
- Used as anti-inflammatory agents when colchicine and NSAIDs are insufficient or contraindicated for acute attacks.
Basic Information on Gout
- Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joint tissue.
- Chronic hyperuricemia, defined as uric acid levels > 7 mg/dL (0.42 mmol/L), is the primary cause.
- Uric acid is the end product of purine metabolism, mainly excreted by the renal proximal convoluted tubule (PCT).
- Certain drugs, such as diuretics, can interfere with uric acid excretion, causing retention.
Causes of Hyperuricemia
- Decreased uric acid excretion accounts for 90% of primary gout cases, often due to:
- Medications (e.g., diuretics, aspirin).
- Kidney diseases.
- Increased uric acid production can result from:
- High-protein diets.
- Treatment of hematologic malignancies, causing tissue breakdown (tumor lysis syndrome).
- Alcohol consumption also contributes as a mixed cause.
Pathogenesis of Gouty Arthritis
- Elevated serum uric acid levels lead to the precipitation of urate crystals in joints, resulting in irritation and inflammation.
- Polymorphonuclear leukocytes (PMNs) and macrophages phagocytize uric acid crystals, causing swelling and inflammation.
- Leukocyte death releases proteolytic enzymes and inflammatory mediators (e.g., LTB4, IL-1), intensifying inflammation.
Uricosuric Drugs: Probenecid
- Probenecid has a biphasic action:
- In small doses, it inhibits tubular secretion of organic acids (including uric acid).
- In larger doses (≥500 mg twice/day), it inhibits tubular reabsorption of uric acid, enhancing its excretion.
- Therapeutic uses include treatment of chronic gout and prolonging the half-life of certain acidic drugs.
- Adverse effects may include gastric irritation, skin rash, and, rarely, interstitial nephritis or aplastic anemia.
- Should not be used during acute gout attacks as it may aggravate inflammation.
Inhibitors of Uric Acid Synthesis: Allopurinol
- Allopurinol is a synthetic purine analogue that inhibits xanthine oxidase, reducing uric acid synthesis.
- It has a long duration of action due to potent inhibition by both the drug and its metabolite.
- Recommended for patients with recurrent gout attacks, targeting uric acid levels of 5 mg/dL (0.3 mmol/L).
- May also be used in hematologic malignancies to prevent hyperuricemia.
- Common adverse effects include gastric irritation and hypersensitivity reactions; can precipitate acute gout at therapy onset.
Increase Uric Acid Metabolism: Pegloticase
- Pegloticase is a recombinant form of porcine uricase, converting uric acid to the soluble allantoin.
- Administered intravenously (8 mg every 2 weeks), it quickly lowers serum uric acid.
- Indicated for severe gout cases resistant to other treatments.
Anti-Inflammatory Drugs: Colchicine
- Colchicine is a plant alkaloid that inhibits leukocyte motility, phagocytosis, and mitosis.
- Mainly used for acute gout attacks; slower onset compared to NSAIDs, with pain relief occurring within 12–24 hours.
- High doses can lead to gastrointestinal toxicity, especially diarrhea.
NSAIDs: Indomethacin and Naproxen
- Indomethacin and naproxen are FDA-approved NSAIDs for acute gout, providing faster relief than colchicine.
- Dosage adjustments may be needed when co-administered with probenecid, which inhibits renal excretion.
Corticosteroids
- Used as anti-inflammatory agents when colchicine and NSAIDs are insufficient or contraindicated for acute attacks.
Basic Information on Gout
- Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joint tissue.
- Chronic hyperuricemia, defined as uric acid levels > 7 mg/dL (0.42 mmol/L), is the primary cause.
- Uric acid is the end product of purine metabolism, mainly excreted by the renal proximal convoluted tubule (PCT).
- Certain drugs, such as diuretics, can interfere with uric acid excretion, causing retention.
Causes of Hyperuricemia
- Decreased uric acid excretion accounts for 90% of primary gout cases, often due to:
- Medications (e.g., diuretics, aspirin).
- Kidney diseases.
- Increased uric acid production can result from:
- High-protein diets.
- Treatment of hematologic malignancies, causing tissue breakdown (tumor lysis syndrome).
- Alcohol consumption also contributes as a mixed cause.
Pathogenesis of Gouty Arthritis
- Elevated serum uric acid levels lead to the precipitation of urate crystals in joints, resulting in irritation and inflammation.
- Polymorphonuclear leukocytes (PMNs) and macrophages phagocytize uric acid crystals, causing swelling and inflammation.
- Leukocyte death releases proteolytic enzymes and inflammatory mediators (e.g., LTB4, IL-1), intensifying inflammation.
Uricosuric Drugs: Probenecid
- Probenecid has a biphasic action:
- In small doses, it inhibits tubular secretion of organic acids (including uric acid).
- In larger doses (≥500 mg twice/day), it inhibits tubular reabsorption of uric acid, enhancing its excretion.
- Therapeutic uses include treatment of chronic gout and prolonging the half-life of certain acidic drugs.
- Adverse effects may include gastric irritation, skin rash, and, rarely, interstitial nephritis or aplastic anemia.
- Should not be used during acute gout attacks as it may aggravate inflammation.
Inhibitors of Uric Acid Synthesis: Allopurinol
- Allopurinol is a synthetic purine analogue that inhibits xanthine oxidase, reducing uric acid synthesis.
- It has a long duration of action due to potent inhibition by both the drug and its metabolite.
- Recommended for patients with recurrent gout attacks, targeting uric acid levels of 5 mg/dL (0.3 mmol/L).
- May also be used in hematologic malignancies to prevent hyperuricemia.
- Common adverse effects include gastric irritation and hypersensitivity reactions; can precipitate acute gout at therapy onset.
Increase Uric Acid Metabolism: Pegloticase
- Pegloticase is a recombinant form of porcine uricase, converting uric acid to the soluble allantoin.
- Administered intravenously (8 mg every 2 weeks), it quickly lowers serum uric acid.
- Indicated for severe gout cases resistant to other treatments.
Anti-Inflammatory Drugs: Colchicine
- Colchicine is a plant alkaloid that inhibits leukocyte motility, phagocytosis, and mitosis.
- Mainly used for acute gout attacks; slower onset compared to NSAIDs, with pain relief occurring within 12–24 hours.
- High doses can lead to gastrointestinal toxicity, especially diarrhea.
NSAIDs: Indomethacin and Naproxen
- Indomethacin and naproxen are FDA-approved NSAIDs for acute gout, providing faster relief than colchicine.
- Dosage adjustments may be needed when co-administered with probenecid, which inhibits renal excretion.
Corticosteroids
- Used as anti-inflammatory agents when colchicine and NSAIDs are insufficient or contraindicated for acute attacks.
Basic Information on Gout
- Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joint tissue.
- Chronic hyperuricemia, defined as uric acid levels > 7 mg/dL (0.42 mmol/L), is the primary cause.
- Uric acid is the end product of purine metabolism, mainly excreted by the renal proximal convoluted tubule (PCT).
- Certain drugs, such as diuretics, can interfere with uric acid excretion, causing retention.
Causes of Hyperuricemia
- Decreased uric acid excretion accounts for 90% of primary gout cases, often due to:
- Medications (e.g., diuretics, aspirin).
- Kidney diseases.
- Increased uric acid production can result from:
- High-protein diets.
- Treatment of hematologic malignancies, causing tissue breakdown (tumor lysis syndrome).
- Alcohol consumption also contributes as a mixed cause.
Pathogenesis of Gouty Arthritis
- Elevated serum uric acid levels lead to the precipitation of urate crystals in joints, resulting in irritation and inflammation.
- Polymorphonuclear leukocytes (PMNs) and macrophages phagocytize uric acid crystals, causing swelling and inflammation.
- Leukocyte death releases proteolytic enzymes and inflammatory mediators (e.g., LTB4, IL-1), intensifying inflammation.
Uricosuric Drugs: Probenecid
- Probenecid has a biphasic action:
- In small doses, it inhibits tubular secretion of organic acids (including uric acid).
- In larger doses (≥500 mg twice/day), it inhibits tubular reabsorption of uric acid, enhancing its excretion.
- Therapeutic uses include treatment of chronic gout and prolonging the half-life of certain acidic drugs.
- Adverse effects may include gastric irritation, skin rash, and, rarely, interstitial nephritis or aplastic anemia.
- Should not be used during acute gout attacks as it may aggravate inflammation.
Inhibitors of Uric Acid Synthesis: Allopurinol
- Allopurinol is a synthetic purine analogue that inhibits xanthine oxidase, reducing uric acid synthesis.
- It has a long duration of action due to potent inhibition by both the drug and its metabolite.
- Recommended for patients with recurrent gout attacks, targeting uric acid levels of 5 mg/dL (0.3 mmol/L).
- May also be used in hematologic malignancies to prevent hyperuricemia.
- Common adverse effects include gastric irritation and hypersensitivity reactions; can precipitate acute gout at therapy onset.
Increase Uric Acid Metabolism: Pegloticase
- Pegloticase is a recombinant form of porcine uricase, converting uric acid to the soluble allantoin.
- Administered intravenously (8 mg every 2 weeks), it quickly lowers serum uric acid.
- Indicated for severe gout cases resistant to other treatments.
Anti-Inflammatory Drugs: Colchicine
- Colchicine is a plant alkaloid that inhibits leukocyte motility, phagocytosis, and mitosis.
- Mainly used for acute gout attacks; slower onset compared to NSAIDs, with pain relief occurring within 12–24 hours.
- High doses can lead to gastrointestinal toxicity, especially diarrhea.
NSAIDs: Indomethacin and Naproxen
- Indomethacin and naproxen are FDA-approved NSAIDs for acute gout, providing faster relief than colchicine.
- Dosage adjustments may be needed when co-administered with probenecid, which inhibits renal excretion.
Corticosteroids
- Used as anti-inflammatory agents when colchicine and NSAIDs are insufficient or contraindicated for acute attacks.
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Description
This quiz explores the role of PNLLs and macrophages in phagocytosing uric acid crystals, resulting in joint swelling and inflammation. It also delves into the impact of leukocytes and their enzymes and inflammatory mediators on the process of arthritis. Test your understanding of the cellular mechanisms behind this condition.
