2. GOUT : a heterogeneous group of diseases usually associated with hyperuricaemia, it is characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate crystals in joints & cartilage ± nephrolithiasis. GOUT : a heterogeneous group of diseases usually associated with hyperuricaemia, it is characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate crystals in joints & cartilage ± nephrolithiasis. Gout = the clinical condition. Gout = the clinical condition. Hyperuricaemia = the biochemical condition, it is generally defined as S.uric acid : Hyperuricaemia = the biochemical condition, it is generally defined as S.uric acid : > 0.47 mmol/L for men. > 0.47 mmol/L for men. > 0.40 mmol/L for postmenopausal women. > 0.40 mmol/L for postmenopausal women. > 0.37 mmol/L for premenopausal women. > 0.37 mmol/L for premenopausal women. GOUT : a heterogeneous group of diseases usually associated with hyperuricaemia, it is characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate crystals in joints & cartilage ± nephrolithiasis. GOUT : a heterogeneous group of diseases usually associated with hyperuricaemia, it is characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate crystals in joints & cartilage ± nephrolithiasis. Gout = the clinical condition. Gout = the clinical condition. Hyperuricaemia = the biochemical condition, it is generally defined as S.uric acid : Hyperuricaemia = the biochemical condition, it is generally defined as S.uric acid : > 0.47 mmol/L for men. > 0.47 mmol/L for men. > 0.40 mmol/L for postmenopausal women. > 0.40 mmol/L for postmenopausal women. > 0.37 mmol/L for premenopausal women. > 0.37 mmol/L for premenopausal women. DEFINITION

3. A disease of middle aged men(95% are men). Prevalence is highly variable according to different societies, environments and dietary habits : in UK = 2.6 per 1000. It is secondary in 10 % (diuretics are the leading cause). A disease of middle aged men(95% are men). Prevalence is highly variable according to different societies, environments and dietary habits : in UK = 2.6 per 1000. It is secondary in 10 % (diuretics are the leading cause). EPIDEMIOLOGY

4. Uric acid is the end product of purine metabolism in humans(in mammals: uricase enzyme degrades uric acid to allantoin). Gout development α degree + duration of hyperuricaemia. There are 2 mechanisms of gout development: Uric acid is the end product of purine metabolism in humans(in mammals: uricase enzyme degrades uric acid to allantoin). Gout development α degree + duration of hyperuricaemia. There are 2 mechanisms of gout development: 1.overproduction of uric acid : a. Increased purine turnover: ●myeloprliferative disorders ●polycythemia ● neoplastic diseases ●chronic haemolytic anaemia ●severe exfoliative psoriasis ●glycogen storage disease ●excessive dietary proteins b. increased purine synthesis de novo: ●HGPRT deficiency ●PRPP synthetase overactivity ●G6Pase deficiency 1.overproduction of uric acid : a. Increased purine turnover: ●myeloprliferative disorders ●polycythemia ● neoplastic diseases ●chronic haemolytic anaemia ●severe exfoliative psoriasis ●glycogen storage disease ●excessive dietary proteins b. increased purine synthesis de novo: ●HGPRT deficiency ●PRPP synthetase overactivity ●G6Pase deficiency AETIOLOGY

5. AETIOLOGY(contd.) 2.Underexcretion of uric acid: 2.Underexcretion of uric acid: a. reduction in renal functional mass a. reduction in renal functional mass ●chronic renal disease ●chronic renal disease b. reduction in GFR b. reduction in GFR ●conditions associated with volume depletion ●conditions associated with volume depletion ●diabetes insipidus ●diabetes insipidus c. reduction in fractional urate clearance c. reduction in fractional urate clearance ●lead poisoning ●lead poisoning ● hypertension ● hypertension ●increased levels of organic acids: ●increased levels of organic acids: -exercise -exercise -starvation and severe vomiting -starvation and severe vomiting 2.Underexcretion of uric acid: 2.Underexcretion of uric acid: a. reduction in renal functional mass a. reduction in renal functional mass ●chronic renal disease ●chronic renal disease b. reduction in GFR b. reduction in GFR ●conditions associated with volume depletion ●conditions associated with volume depletion ●diabetes insipidus ●diabetes insipidus c. reduction in fractional urate clearance c. reduction in fractional urate clearance ●lead poisoning ●lead poisoning ● hypertension ● hypertension ●increased levels of organic acids: ●increased levels of organic acids: -exercise -exercise -starvation and severe vomiting -starvation and severe vomiting -alcohol -alcohol -diabetic ketoacidosis -diabetic ketoacidosis d. drug administration ●low dose aspirin ●diuretics ●phenylbutazone ●sulphinpyrazone ●pyrazinamide ●ethambutol -alcohol -alcohol -diabetic ketoacidosis -diabetic ketoacidosis d. drug administration ●low dose aspirin ●diuretics ●phenylbutazone ●sulphinpyrazone ●pyrazinamide ●ethambutol

6. The natural history of gout has 4 stages: 1. Asymptomatic hyperuricaemia 2. Acute gouty arthritis 3. Intercritical period 4. Chronic tophaceous gout The natural history of gout has 4 stages: 1. Asymptomatic hyperuricaemia 2. Acute gouty arthritis 3. Intercritical period 4. Chronic tophaceous gout CLINICAL MANIFESTATIONS

7. Is that stage in which the S. urate is raised but arthritic symptoms, tophi, or uric acid stones have not yet appeared. While virtually all gouty subjects are hyperuricemic, only about 5% of hyperuricemics ever develop gout. The phase of asymptomatic hyperuricemia ends with the first attack of gouty arthritis or nephrolithiasis. In most, gout comes before stone, usually after at least 20-30 years of sustained hyperuricemia. Is that stage in which the S. urate is raised but arthritic symptoms, tophi, or uric acid stones have not yet appeared. While virtually all gouty subjects are hyperuricemic, only about 5% of hyperuricemics ever develop gout. The phase of asymptomatic hyperuricemia ends with the first attack of gouty arthritis or nephrolithiasis. In most, gout comes before stone, usually after at least 20-30 years of sustained hyperuricemia. 1. Asymptomatic hyperuricaemia

8. usually monoarticular with 80% having their 1 st attack in the great toe(podagra). Other joints may be affected e.g. small joints of feet & ankles, hands(DIP), elbows and knees. Pt. complains of severe pain with a hot, red, swollen & extremely tender joints, the weight of the bedclothes is unbearable & walking with weight bearing is impossible. Constitutional symptoms(e.g. fever) may present. Untreated attack may last days or weeks before subsiding spontaneously, and resolution may be accompanied by pruritis & desequamation of the overlying skin. usually monoarticular with 80% having their 1 st attack in the great toe(podagra). Other joints may be affected e.g. small joints of feet & ankles, hands(DIP), elbows and knees. Pt. complains of severe pain with a hot, red, swollen & extremely tender joints, the weight of the bedclothes is unbearable & walking with weight bearing is impossible. Constitutional symptoms(e.g. fever) may present. Untreated attack may last days or weeks before subsiding spontaneously, and resolution may be accompanied by pruritis & desequamation of the overlying skin. 2. Acute gouty arthritis

11. Trauma. Unusual physical exercise. Surgery. Severe systemic illness. Severe dieting. Dietary excess. Alcohol. Drugs : -diuretics. -initiation of uricosuric or allopurinol therapy. -initiation of B12 in pernicious anaemia. -following drug allergy. -cytotoxic drug therapy. Trauma. Unusual physical exercise. Surgery. Severe systemic illness. Severe dieting. Dietary excess. Alcohol. Drugs : -diuretics. -initiation of uricosuric or allopurinol therapy. -initiation of B12 in pernicious anaemia. -following drug allergy. -cytotoxic drug therapy. Events provoking acute gouty arthritis

12. Gouty attack may last 1 day- several weeks but characteristically subside spontaneously with complete resolution. An asymptomatic phase = intercritical period then commences. The pt. is totally free of symptoms during this stage, a feature that is diagnostically important. Approximately 7 % of pt.s never have a 2 nd attack, while 60 % experience a recurrence within 1 year. Gouty attack may last 1 day- several weeks but characteristically subside spontaneously with complete resolution. An asymptomatic phase = intercritical period then commences. The pt. is totally free of symptoms during this stage, a feature that is diagnostically important. Approximately 7 % of pt.s never have a 2 nd attack, while 60 % experience a recurrence within 1 year. 3. Intercritical period

13. Inevitably follows recurrent acute attacks. Associated with tophi & renal disease. Characterized by asymmetrical jt. Swelling. Tophi commonly occur in periarticular tissues, the cartilage of the ear, bursae and tendon sheaths. Inevitably follows recurrent acute attacks. Associated with tophi & renal disease. Characterized by asymmetrical jt. Swelling. Tophi commonly occur in periarticular tissues, the cartilage of the ear, bursae and tendon sheaths. 4. Chronic tophaceous gout

15. S. uric acid: usually ↑, but may be normal. Exam. of synovial fluid aspirated from inflamed jt. is confirmative : monosodium urate (MSU) crystals are needle-shaped, negatively birefringent under polarizing microscopy ± synovial fluid polymorpho- nuclear leucocytosis. S. uric acid: usually ↑, but may be normal. Exam. of synovial fluid aspirated from inflamed jt. is confirmative : monosodium urate (MSU) crystals are needle-shaped, negatively birefringent under polarizing microscopy ± synovial fluid polymorpho- nuclear leucocytosis. INVESTIGATIONS

16. Rest & pt. education. Start Rx as early as you can. Avoid aspirin and its derivatives. Do not use urate-lowering agent( allopurinol or uricosuric drugs) in the acute phase. Medications : NSAIDs : 1 st line Rx, administered in high dosage for the 1 st 3 days or until pain settled, then continued until all symptoms & signs have resolved(7-10 days). -Indomethacin 75-100 mg twice daily, reduced after 5 days. Adverse effects include headache, mental changes & GI upset. -Naproxen starting with 750 mg followed by 250 mg 3 times/day. -Piroxicam 40 mg/day followed by 10-20 mg/day. -Diclofenac 100 mg, then 50 mg 3 times/day for 48 hrs., then 50 mg twice daily for 8 days. Rest & pt. education. Start Rx as early as you can. Avoid aspirin and its derivatives. Do not use urate-lowering agent( allopurinol or uricosuric drugs) in the acute phase. Medications : NSAIDs : 1 st line Rx, administered in high dosage for the 1 st 3 days or until pain settled, then continued until all symptoms & signs have resolved(7-10 days). -Indomethacin 75-100 mg twice daily, reduced after 5 days. Adverse effects include headache, mental changes & GI upset. -Naproxen starting with 750 mg followed by 250 mg 3 times/day. -Piroxicam 40 mg/day followed by 10-20 mg/day. -Diclofenac 100 mg, then 50 mg 3 times/day for 48 hrs., then 50 mg twice daily for 8 days. TREATMENT : acute attack

17. Colchicine: Colchicine: Effective & specific gout Rx, but less favored than NSAIDs because of slow onset of action & high incidence of side effects. Effective & specific gout Rx, but less favored than NSAIDs because of slow onset of action & high incidence of side effects. For oral colchicine to be effective it must be administered as quickly as possible. For oral colchicine to be effective it must be administered as quickly as possible. Initial dose= 1mg followed by 0.5mg/2-3hrs until there is relief of jt. Pain, or the pt. develop GI symptoms or has received a max. dose of 6mg. Initial dose= 1mg followed by 0.5mg/2-3hrs until there is relief of jt. Pain, or the pt. develop GI symptoms or has received a max. dose of 6mg. Therapeutic dose is very close to toxic dose. death have occurred in pt.s received as little as 5mg of colchicine. Therapeutic dose is very close to toxic dose. death have occurred in pt.s received as little as 5mg of colchicine. Therapeutic response commence after 6hrs,with pain relief after 12 hrs and resolution of pain,redness &swelling in 75% of pt.s after 48-72hrs(a diagnostic value). Colchicine course should not be repeated within 3days to avoid toxic reaction. Therapeutic response commence after 6hrs,with pain relief after 12 hrs and resolution of pain,redness &swelling in 75% of pt.s after 48-72hrs(a diagnostic value). Colchicine course should not be repeated within 3days to avoid toxic reaction. S/E include: severe nausea & vomiting,diarrhoea&abd.pain(in 80% of pt.s), dehydration, seizures, resp. depression, hepatic & muscle necrosis, renal damage, fever, granulocytopenia, aplastic anaemia, DIC and alopecia. S/E include: severe nausea & vomiting,diarrhoea&abd.pain(in 80% of pt.s), dehydration, seizures, resp. depression, hepatic & muscle necrosis, renal damage, fever, granulocytopenia, aplastic anaemia, DIC and alopecia. Colchicine distribution occurs quickly, and after a single dose only 10% is excreted within the 1 st 24 hrs. & its half life= 30 hrs. Colchicine distribution occurs quickly, and after a single dose only 10% is excreted within the 1 st 24 hrs. & its half life= 30 hrs. It would be reasonable to give the pt. 1 or 2 doses of opiod analgesic(e.g. morphine10mg) while awaiting the analgesic effect of NSAIDs or colchicine. It would be reasonable to give the pt. 1 or 2 doses of opiod analgesic(e.g. morphine10mg) while awaiting the analgesic effect of NSAIDs or colchicine. I.V. colchicine is no longer licensed for use because it has been associated with severe toxicity. I.V. colchicine is no longer licensed for use because it has been associated with severe toxicity. Colchicine: Colchicine: Effective & specific gout Rx, but less favored than NSAIDs because of slow onset of action & high incidence of side effects. Effective & specific gout Rx, but less favored than NSAIDs because of slow onset of action & high incidence of side effects. For oral colchicine to be effective it must be administered as quickly as possible. For oral colchicine to be effective it must be administered as quickly as possible. Initial dose= 1mg followed by 0.5mg/2-3hrs until there is relief of jt. Pain, or the pt. develop GI symptoms or has received a max. dose of 6mg. Initial dose= 1mg followed by 0.5mg/2-3hrs until there is relief of jt. Pain, or the pt. develop GI symptoms or has received a max. dose of 6mg. Therapeutic dose is very close to toxic dose. death have occurred in pt.s received as little as 5mg of colchicine. Therapeutic dose is very close to toxic dose. death have occurred in pt.s received as little as 5mg of colchicine. Therapeutic response commence after 6hrs,with pain relief after 12 hrs and resolution of pain,redness &swelling in 75% of pt.s after 48-72hrs(a diagnostic value). Colchicine course should not be repeated within 3days to avoid toxic reaction. Therapeutic response commence after 6hrs,with pain relief after 12 hrs and resolution of pain,redness &swelling in 75% of pt.s after 48-72hrs(a diagnostic value). Colchicine course should not be repeated within 3days to avoid toxic reaction. S/E include: severe nausea & vomiting,diarrhoea&abd.pain(in 80% of pt.s), dehydration, seizures, resp. depression, hepatic & muscle necrosis, renal damage, fever, granulocytopenia, aplastic anaemia, DIC and alopecia. S/E include: severe nausea & vomiting,diarrhoea&abd.pain(in 80% of pt.s), dehydration, seizures, resp. depression, hepatic & muscle necrosis, renal damage, fever, granulocytopenia, aplastic anaemia, DIC and alopecia. Colchicine distribution occurs quickly, and after a single dose only 10% is excreted within the 1 st 24 hrs. & its half life= 30 hrs. Colchicine distribution occurs quickly, and after a single dose only 10% is excreted within the 1 st 24 hrs. & its half life= 30 hrs. It would be reasonable to give the pt. 1 or 2 doses of opiod analgesic(e.g. morphine10mg) while awaiting the analgesic effect of NSAIDs or colchicine. It would be reasonable to give the pt. 1 or 2 doses of opiod analgesic(e.g. morphine10mg) while awaiting the analgesic effect of NSAIDs or colchicine. I.V. colchicine is no longer licensed for use because it has been associated with severe toxicity. I.V. colchicine is no longer licensed for use because it has been associated with severe toxicity. TREATMENT : acute attack(contd.)

18. Steroids: Intra-articular steroids: can provide quick relief if only 1 or 2 jt.s are involved, however the Diff.Dx between septic arthritis &gouty arthritis must be certain before injection. Systemic steroids: can be used in certain pt.s e.g. those with severe or polyarticular disease or those with renal disease or heart failure. Prednisolone 20-40mg/day for 1-3 wk.s. alternatively I.V. methylprednisolone 50-150 mg/day or I.M. triamcinolone 40-100 mg/day may be administered and tapered over 5 days. Steroids: Intra-articular steroids: can provide quick relief if only 1 or 2 jt.s are involved, however the Diff.Dx between septic arthritis &gouty arthritis must be certain before injection. Systemic steroids: can be used in certain pt.s e.g. those with severe or polyarticular disease or those with renal disease or heart failure. Prednisolone 20-40mg/day for 1-3 wk.s. alternatively I.V. methylprednisolone 50-150 mg/day or I.M. triamcinolone 40-100 mg/day may be administered and tapered over 5 days. TREATMENT : acute attack(contd.)

19. Indicated for pt.s with : recurrent acute attacks of gout = > 2 attacks / year, gout+tophi or evidence of chronic arthritis, associated renal disease and gout+markedly ↑ s.uric acid >0.54mmol/l, 9mg/100 ml. (but not indicated for asymptomatic hyperuricaemic pt.s) Indicated for pt.s with : recurrent acute attacks of gout = > 2 attacks / year, gout+tophi or evidence of chronic arthritis, associated renal disease and gout+markedly ↑ s.uric acid >0.54mmol/l, 9mg/100 ml. (but not indicated for asymptomatic hyperuricaemic pt.s) Allopurinol : the agent of choice Allopurinol : the agent of choice -reduce uric acid production by inhibiting the enzyme xanthine oxidase. It is not active but converted(60-70 %)in liver to its active metabolite oxipurinol. -reduce uric acid production by inhibiting the enzyme xanthine oxidase. It is not active but converted(60-70 %)in liver to its active metabolite oxipurinol. -t 1/2 of allopurinol is 2 hrs, but that of oxipurinol is 12-30 hrs. -t 1/2 of allopurinol is 2 hrs, but that of oxipurinol is 12-30 hrs. -initial dose in pt. with normal renal function should not exceed 300mg/day. Practically most pt.s are started on 100mg/day, and the usual maintenance dose is 100-600 mg/day. The dose should be titrated according to creatinine clearance: -initial dose in pt. with normal renal function should not exceed 300mg/day. Practically most pt.s are started on 100mg/day, and the usual maintenance dose is 100-600 mg/day. The dose should be titrated according to creatinine clearance: creatinine clearance( ml/min) allopurinol dose creatinine clearance( ml/min) allopurinol dose 0 …………………………………………… 100 mg thrice weekly 0 …………………………………………… 100 mg thrice weekly 10 …………………………………………… 100mg alternate days 10 …………………………………………… 100mg alternate days 20 …………………………………………… 100 mg daily 20 …………………………………………… 100 mg daily 40 …………………………………………… 150 mg daily 40 …………………………………………… 150 mg daily 60 …………………………………………… 200 mg daily 60 …………………………………………… 200 mg daily >100 ………………………………………….. 300 mg daily >100 ………………………………………….. 300 mg daily Indicated for pt.s with : recurrent acute attacks of gout = > 2 attacks / year, gout+tophi or evidence of chronic arthritis, associated renal disease and gout+markedly ↑ s.uric acid >0.54mmol/l, 9mg/100 ml. (but not indicated for asymptomatic hyperuricaemic pt.s) Indicated for pt.s with : recurrent acute attacks of gout = > 2 attacks / year, gout+tophi or evidence of chronic arthritis, associated renal disease and gout+markedly ↑ s.uric acid >0.54mmol/l, 9mg/100 ml. (but not indicated for asymptomatic hyperuricaemic pt.s) Allopurinol : the agent of choice Allopurinol : the agent of choice -reduce uric acid production by inhibiting the enzyme xanthine oxidase. It is not active but converted(60-70 %)in liver to its active metabolite oxipurinol. -reduce uric acid production by inhibiting the enzyme xanthine oxidase. It is not active but converted(60-70 %)in liver to its active metabolite oxipurinol. -t 1/2 of allopurinol is 2 hrs, but that of oxipurinol is 12-30 hrs. -t 1/2 of allopurinol is 2 hrs, but that of oxipurinol is 12-30 hrs. -initial dose in pt. with normal renal function should not exceed 300mg/day. Practically most pt.s are started on 100mg/day, and the usual maintenance dose is 100-600 mg/day. The dose should be titrated according to creatinine clearance: -initial dose in pt. with normal renal function should not exceed 300mg/day. Practically most pt.s are started on 100mg/day, and the usual maintenance dose is 100-600 mg/day. The dose should be titrated according to creatinine clearance: creatinine clearance( ml/min) allopurinol dose creatinine clearance( ml/min) allopurinol dose 0 …………………………………………… 100 mg thrice weekly 0 …………………………………………… 100 mg thrice weekly 10 …………………………………………… 100mg alternate days 10 …………………………………………… 100mg alternate days 20 …………………………………………… 100 mg daily 20 …………………………………………… 100 mg daily 40 …………………………………………… 150 mg daily 40 …………………………………………… 150 mg daily 60 …………………………………………… 200 mg daily 60 …………………………………………… 200 mg daily >100 ………………………………………….. 300 mg daily >100 ………………………………………….. 300 mg daily TREATMENT: prophylactic control of symptomatic hyperuricamia

20. Allopurinol(contd.): -S/E occur in 3-5 % mostly in form of hypersensitivity reaction. skin eruptions are the most common, and others include hepatotoxicity, acute interstitial nephritis& fever. These hypersensitivity reactions subside upon Rx discontinuation. However if Rx continued, severe exfoliative dermatitis, various haematological abnormalities, hepatomegaly, jaundice,hepatic necrosis &renal impairment may occur. A syndrome of allopurinol toxicity including rash,fever, worsening renal insufficiency, vasculitis &death has been reported. Allopurinol(contd.): -S/E occur in 3-5 % mostly in form of hypersensitivity reaction. skin eruptions are the most common, and others include hepatotoxicity, acute interstitial nephritis& fever. These hypersensitivity reactions subside upon Rx discontinuation. However if Rx continued, severe exfoliative dermatitis, various haematological abnormalities, hepatomegaly, jaundice,hepatic necrosis &renal impairment may occur. A syndrome of allopurinol toxicity including rash,fever, worsening renal insufficiency, vasculitis &death has been reported.

21. Azapropazone : A NSAID that lowers serum urate level, its use is restricted to acute gout only when other NSAIDs have been tried & failed. Contraindicated in Hx of peptic ulceration & in renal impairment. Max.dose=1.8 g/day until symptoms subside, followed by 1.2 g/day until symptoms resolve. Azapropazone : A NSAID that lowers serum urate level, its use is restricted to acute gout only when other NSAIDs have been tried & failed. Contraindicated in Hx of peptic ulceration & in renal impairment. Max.dose=1.8 g/day until symptoms subside, followed by 1.2 g/day until symptoms resolve.

22. Uricosuric agents: Uricosuric agents: -probenecid(500mg-1g twice daily)& sulphinpyrazone(100mg 3-4 times/day). -probenecid(500mg-1g twice daily)& sulphinpyrazone(100mg 3-4 times/day). -Ideal for pt.s with uric acid underexcretion, & should be avoided in pt.s with urate nephropathy & those who overproduce uric acid. They are ineffective in pt.s with poor renal function. -Ideal for pt.s with uric acid underexcretion, & should be avoided in pt.s with urate nephropathy & those who overproduce uric acid. They are ineffective in pt.s with poor renal function. -probenecid is well-absorbed orally, with t1/2= 6-12 hr.s. Therapy initiated with 250mg twice/day & increased to 500mg twice/day after 2 wks up to 2 g/day if required. -probenecid is well-absorbed orally, with t1/2= 6-12 hr.s. Therapy initiated with 250mg twice/day & increased to 500mg twice/day after 2 wks up to 2 g/day if required. -pt.s should be advised to maintain high fluid intake(at least 2 liters/day) to minimize the risk of stone formation. -pt.s should be advised to maintain high fluid intake(at least 2 liters/day) to minimize the risk of stone formation. -S/E occur in 5-10% : nausea, heartburn, flatulence or constipation. -S/E occur in 5-10% : nausea, heartburn, flatulence or constipation. -Its major limiting factor is a lack of efficacy due to poor compliance, concurrent low dose aspirin or renal insufficiency. -Its major limiting factor is a lack of efficacy due to poor compliance, concurrent low dose aspirin or renal insufficiency. Uricosuric agents: Uricosuric agents: -probenecid(500mg-1g twice daily)& sulphinpyrazone(100mg 3-4 times/day). -probenecid(500mg-1g twice daily)& sulphinpyrazone(100mg 3-4 times/day). -Ideal for pt.s with uric acid underexcretion, & should be avoided in pt.s with urate nephropathy & those who overproduce uric acid. They are ineffective in pt.s with poor renal function. -Ideal for pt.s with uric acid underexcretion, & should be avoided in pt.s with urate nephropathy & those who overproduce uric acid. They are ineffective in pt.s with poor renal function. -probenecid is well-absorbed orally, with t1/2= 6-12 hr.s. Therapy initiated with 250mg twice/day & increased to 500mg twice/day after 2 wks up to 2 g/day if required. -probenecid is well-absorbed orally, with t1/2= 6-12 hr.s. Therapy initiated with 250mg twice/day & increased to 500mg twice/day after 2 wks up to 2 g/day if required. -pt.s should be advised to maintain high fluid intake(at least 2 liters/day) to minimize the risk of stone formation. -pt.s should be advised to maintain high fluid intake(at least 2 liters/day) to minimize the risk of stone formation. -S/E occur in 5-10% : nausea, heartburn, flatulence or constipation. -S/E occur in 5-10% : nausea, heartburn, flatulence or constipation. -Its major limiting factor is a lack of efficacy due to poor compliance, concurrent low dose aspirin or renal insufficiency. -Its major limiting factor is a lack of efficacy due to poor compliance, concurrent low dose aspirin or renal insufficiency.

23. Interacting drug affected drug effect Allopurinol azathioprine ↑levels of azathioprine Allopurinol mercaptopurine ↑levels of mercaptopurine Allopurinol anticoagulants enhanced anticoag. effect Aspirin(low dose) uricosurics ↓ hypouricaemic effect Probenecid indomethacin ↑levels of indomethacin = ketoprofen = = ketoprofen = naproxen = = naproxen = methotrexate = = methotrexate = zidovudine = = zidovudine = cephalosporines = = cephalosporines = dapsone = = dapsone = aspirin = = aspirin Sulphinpyrazone anticoagulants enhanced anticoag. effect Interacting drug affected drug effect Allopurinol azathioprine ↑levels of azathioprine Allopurinol mercaptopurine ↑levels of mercaptopurine Allopurinol anticoagulants enhanced anticoag. effect Aspirin(low dose) uricosurics ↓ hypouricaemic effect Probenecid indomethacin ↑levels of indomethacin = ketoprofen = = ketoprofen = naproxen = = naproxen = methotrexate = = methotrexate = zidovudine = = zidovudine = cephalosporines = = cephalosporines = dapsone = = dapsone = aspirin = = aspirin Sulphinpyrazone anticoagulants enhanced anticoag. effect Common drug interactions associated with therapy for gout and hyperuricaemia

24. problem Possible solution Elderly pt. May not tolerate NSAIDs. Colchicine in low dose or corticosteroids are an option. Renal failure pt. Avoid NSAIDs. Heart failure pt. Use colchicine in low dose with caution. Corticosteroids is an option, but use with care in diabetic pt. Hx of GI problems NSAIDs with gastroprotective agent e.g. proton pump inhibitors or misoprostol. Consider colchicine.

25. Elderly pt. Uricosuric agents are rarely effective in the elderly due to reduced renal function. Renal failure pt. Uricosuric agents are not effective. Allopurinol dosage should be reduced. Recurrent attacks Allopurinol dosage should be reduced if creatinine clearance is reduced.

26. “Gout is Like Matches” NSAID – puts out the fire. Colchicine prophylaxis – keeps matches damp. Xanthine oxidase inhibitors and uricosurics – removes the matches. NSAID – puts out the fire. Colchicine prophylaxis – keeps matches damp. Xanthine oxidase inhibitors and uricosurics – removes the matches.

27. THANK YOU