2. 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.)

3. 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.)

4. 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

5. 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.

6. 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.