Rheumatoid arthritis and gout

50 %
50 %
Information about Rheumatoid arthritis and gout
Education

Published on October 21, 2018

Author: drlokendra

Source: authorstream.com

Slide1: Rheumatoid arthritis and gout . Prof Dr Lokendra Sharma Department of Pharmacology, SMS Medical College Jaipur Slide2: Early RA: First few months of symptoms Rheumatoid Nodules: http://www.archrheumatol.net/atlas/case31.html Rheumatoid Nodules Slide4: Rheumatoid Arthritis: Hands 5 Months of Disease 5 Years of Disease Slide5: Rheumatoid Arthritis: 10 Years Later Slide6: Rheumatoid Arthritis: Feet Rheumatoid Arthritis: : Rheumatoid Arthritis: A systemic autoimmune disease unknown cause Synovial tissues proliferate erosions of bone . RA Epidemiology: : RA Epidemiology: 2x4 time women child-bearing age ‘Rare’ in men < 45 years On the Terrace, 1878 DMARDs: DMARDs Conventional Methotrexate Hydrochloroquine Sulfasalazine Leflunomide Gold Azathioprine Minocycline Cyclophasphamide –severe RA Biologicals Etanercept Infliximab Anakinra Adalimumab Abatacept Rituximab Prosorba column- severe RA,Psoriatic A Slide11: DMARDS Mechanism AE & Risk Approximate time to benefit Month/weak Dose Comments/ MCQ Diet Glucosemene & condrotin Pain relief Methotrexate Antimetobolite DNA Synthsis Cell division Hepatoxicity , Myelotoxioity fibrosing alveolitis 1-2M 5-25mg/wk Ist line Sulfasalazine Antimetabolite & Antimalarial Hepatoxicity , myelotoxicity Hypersensitivity reactions 1-3M 2-4g/day Oligospermia , Pro drug Slide12: DMARDS AE & Risk Appoximate time to benefit Month/weak Dose Comment/MCQ Antimalarial ( Hydrochloroquine ) Interfere with Antigen processing Retinopathy Macular damage (HCQ) 2-6 M 200-400 mg/day Leflunamide Blocks T- Cell division Hepatotoxicity , Myelotoxicity , Hypertension 4-12 wk 10-20mg/day Gold salt ( Parentral ) unknown Hypersensitivity, Nephritis fibrosing alveolitis 3-6M 50mg/month 1m Auranofin (Oral Gold) unknown Diarrhoea , Hypersencentivity reaction 4-6m 3mg twice a day Cyclosporin T-cell activity intibitor Nephrotoxicity , Hypertension 6-12wk 150-300mg/day Severe active RA not responde MTX Slide13: DMARDS AE & Risk Appoximate time to benefit Month/weak Doge MCQ Azathioprime Cytostatic Hapatotoxicity , Myelotoxicle Gastrointestinal 2-3m 50-150mg/day Not1 st line, active RA, with SLA Bucillamine Proteinuria , Hepatotoxic , Mylosupression 1-3m 100-200mg/day Tacrolimus Renal insuff , HT, Anemia, Impaired glucose tolerance 6-12 wk 3mg/day D- Penicillamine Unknown alter T-cell function Myelosuph , proteinurea , Nephrotoxic 3-6m 250-750mg/day Persistent active disease Minocycline Hyperpigmintation , dizziness,vaginal yeast infection 1-3m 100mg BD Biological DMARDS: Biological DMARDS Anti – TNFx Dose Command Structure Use Anti TNFx SE Etanercept Infliximab Adalimumab Certolizumab Golimumab 50mg/wk/sc 3mg/kg/8wk 40mg/2wk sc 200 mg/2wk sc 50mg/4wk sc Decoy (R) for TNFx RA & Crohns dz antibody to TNF given with MTX Human fusion protein Mouse/human MaB Fully human MaB RA, JRA, Psoritic arthritis ankylosing spondelytis crohns disease Infection CHF Neurological Malignancy Autoimmunity Hematological Hypersencitivity Anti-B-cell therapy Rituximab 1000mg/repeat after 2 wk Premedication Methylprednisolone Chlorphenaramine PCM Biological DMARDS: Biological DMARDS Anti – TNFx Dose Command Structure Inhibitory of T-cell activation abatacept 125mg sc/wk Favorable safety profile Anti-1L6 Tocilizumab 8mg/kg/4wk More effective than anti TNF in MTx intolerant patients Anti 1L-1 blocking agent Anakinra IL-1 trap 100 mg /sc /daily Phase I Less effective Recombinant form of human 1L-1 Ra Extra-articular RA: Extra-articular RA Subcutaneous nodules Pleural/Pericardial Disease Sjogren’s Syndrome Felty’s Syndrome Vasculitis Slide17: Joint Distribution: RA Compared to OA Rheumatoid Arthritis Osteoarthritis Stevens-Johnson syndrome: Stevens-Johnson syndrome target skin lesions mucous membrane erosions epidermal necrosis with skin detachment Redness and Swelling of Acute Gouty Attack: Redness and Swelling of Acute Gouty Attack http://medicine.ucsd.edu/clinicalimg/extremities-gout.jpg Tophaceous Deposits of Urate: Tophaceous Deposits of Urate http://arthritis.about.com/od/goutdiag/ Gout - acute arthritis: Gout - acute arthritis acute synovitis, ankle & first MTP joints Gout - acute bursitis: Gout - acute bursitis acute olecranon bursitis Gout - acute arthritis: Gout - acute arthritis acute synovitis, ankle & first MTP joints Arthrocentesis Chronic tophaceous gout: Chronic tophaceous gout tophus = localized deposit of monosodium urate crystals Gout - tophus: Gout - tophus Classic location of tophi on helix of ear Gout - X-ray changes: Gout - X-ray changes DIP joint destruction phalangeal bone cysts Gout - X-ray changes: Gout - X-ray changes bony erosions Slide28: Treatment of Gout Slide29: Drugs Used for Therapy of Gout Slide30: DMARDS Mechanism AE & Risk Use Colchicine Interfere with PMN Gastrointestinal Hamatological ( agran & apla ) Muscle weekness High dose acute gout with allopurinol and probenacid Low dose prevent recurence NSAID Inhibit PG Probenacid Inhibit urate excretion Induce acute attach Decrese secretion of anionic drugs Allopurinol 100 &300mg Inhibit xanthine oxidase Rash , abn liver function,GIT ,marrow supp,vasculitis,Toxic epi nec Chronic Gout With chemotherapy Recurrent renal Ca oxalate stone Febuxostat Oral xanthine oxidase inhibitors Minimal ADR use in renal patient Drugs Increasing Risk of Toxicity: Drugs Increasing Risk of Toxicity Macrolide antibiotic Azole antifungals Calcium channel blockers Amiodarone Cyclosporin Statins Slide32: Urate Lowering Therapy Estimation of 24-hr Urinary Uric Acid: Estimation of 24-hr Urinary Uric Acid Indications: Gout in men less than 25 years premenopausal women Urate Lowering Therapy: Indications…: Urate Lowering Therapy: Indications… > 3 attacks per year 2/yr if disabling, prolonged, interferes with ADL Clinical or radiographic signs of chronic gouty joint disease Gout with renal insufficiency Urinary uric acid excretion >1100 mg/day (6.5 mmol) Urate Lowering Therapy: Indications: Urate Lowering Therapy: Indications Serum uric acid persistently >10.1 Tophi in soft tissues or subchondral bone Recurrent urate urolithiasis ? Strong family history of gout Goals of Therapy: Goals of Therapy Serum urate <6 mg/dL (<357 µmol/L) <5 mg/dL (<297 µmol/L) in patients with tophi A fall of <0.6 mg/mo ensures recurrence free achievement of target General Principles: General Principles Should not be initiated during an attack Conventional interval: 4 wk Exceptions: Inter-critical interval <4 wk Chronic tophaceous gout Titrated against serum urate at 3 to 4 wks Treatment should be Continuous Duration: indefinite Choice of Drugs: Choice of Drugs Xanthine oxidase inhibitors: allopurinol, febuxostat Uricosuric drugs: probenecid, sulfinpyrazone, benzbromarone Uricase: pegloticase (porcine), rasburicase (recombinant) Allopurinol: Allopurinol Urate-lowering drug of general choice Particularly suitable for overproducers Started with 100 mg/day single dose after meals with plenty of fluid Doses >300 mg divided Increased at 2 to 3 wks by 100 mg till target reached Maximum: 900 mg/day Monitoring parameters CBC, serum uric acid, ALT, S Cr, at start of therapy Allopurinol: Adverse Effects: Allopurinol: Adverse Effects Diarrhea, and drug fever Rashes, rarely TEN and Steven Johnsons Association: HLA- B*5801 Leukopenia or thrombocytopenia Interstitial nephritis, vasculitis Allopurinol hypersensitivity syndrome (AHS): erythematous rash, fever, eosinophilia, hepatitis, and acute renal failure Rare but life-threatening, mortality 25% Starting Dose and Titration of Allopurinol on eGFR: Starting Dose and Titration of Allopurinol on eGFR eGFR Starting dose Titration ≥60 ml/min 100 mg/day 100 mg every 2-3 wk 30-59 ml/min 100 mg/day 50 mg every 2-3 wk 10-29 ml/min 50 mg/day 50 mg every 2-3 wk Slide42: Rational Treatment in Two Phases : Phase I – control pain and inflammation:      NSAIDs (ibuprofen – may use indomethacin ) or colchicine   Phase II – decrease the serum urate (< 4.0 mg/ dL ) > 800 mg in 24 hr urine suggests overproduction – use allopurinol < 500 mg in 24 hr urine suggests decreased renal clearance – use probenecid Febuxostat: Febuxostat investigational agent (NDA 12/2004) oral xanthine oxidase inhibitor chemically distinct from allopurinol 94% of patients reached urate < 6.0 mg/dl minimal adverse events can be used in patients with renal disease Febuxostat… : Febuxostat… Indications: Intolerance/allergy to allopurinol Mild to moderate CKD 40 mg produces a reduction equivalent to 300 mg allopurinol Started at 40 mg/day Increased to 80 mg if target not reached after 2 wks Maximum recommended dose 120 mg Febuxostat: Febuxostat AEs: liver function abnormalities Nausea arthralgia rash Monitoring: transaminases Uricosuric Drugs: Uricosuric Drugs Indication: Intolerance to allopurinol Requisite: 24-hr urinary uric acid <800 mg Contra-indications: Nephrolithiasis or uric acid nephropathy Uric acid overproduction Renal insufficiency Extensive tophi 1. Most common cause of Moebius syndrome is use of which of the following drug in pregnancy?: 1. Most common cause of Moebius syndrome is use of which of the following drug in pregnancy? a. Misoprostol b. Thalidomide c. Methotrexate d. Dinoprostone (a) 2. Which of the following drugs cause oligospermia?: 2. Which of the following drugs cause oligospermia? a. Leflunomide b. D-Penicillamine c. Methotrexate d. Sulfasalazine (d) 3.Allopurinol prevents conversion of: 3.Allopurinol prevents conversion of a. Hypoxanthine to xanthine b. Xanthine to hypoxanthine c. Hypoxanthine to I.M.P. d. Xanthine to uric acid (a) 4.Which of the following NSAIDs has been approved for use in children?: 4.Which of the following NSAIDs has been approved for use in children? a. Indomethacin b. Ibuprofen c. Ketorolac d. Piroxicam (b) 5.Which of the following disease modifying anti-rheumatoid drugs is a prodrug?: 5.Which of the following disease modifying anti-rheumatoid drugs is a prodrug? a. Etanercept b. Nimesulide c. Sulfasalazine d. Colchicine (c) 6. All of the following drugs can produce hyperuricemia EXCEPT : 6. All of the following drugs can produce hyperuricemia EXCEPT a. Ethambutol b. Pyrazinamide c. Sulfinpyrazone d. Hydrochlorothiazide © 7. Drug of choice for acute gout is: 7. Drug of choice for acute gout is a. Colchicine b. Indomethacin c. Allopurinol d. Dexamethasone (b) 8. Most common dose limiting adverse effect of colchicine is: 8. Most common dose limiting adverse effect of colchicine is a. Sedation b. Kidney damage c. Diarrhea d. Muscle paralysis © 9. Which of the following drugs is useful in chronic gout but is NOT a uricosuric agent?: 9. Which of the following drugs is useful in chronic gout but is NOT a uricosuric agent? a. Probenecid b. Phenylbutazone c. Sulfinpyrazone d. Allopurinol (d) 10. Allopurinol is useful in all of the following conditions EXCEPT: 10. Allopurinol is useful in all of the following conditions EXCEPT a. Cancer chemotherapy induced hyperuricemia b. Hydrochlorothiazide induced hyperuricemia c. Acute gouty arthritis d. Kala –azar © 11. Rasburicase is a newer drug used in gout. It act by: 11. Rasburicase is a newer drug used in gout. It act by a. Decreasing urate synthesis b. Increasing urate oxidation c. Decreasing intestinal absorption of uric acid d. Increasing renal excretion of uric acid (b) 12. A drug that is effective for rheumatoid arthritis but is not appropriate for osteoarthritis is: 12. A drug that is effective for rheumatoid arthritis but is not appropriate for osteoarthritis is a. Acetaminophen b. Infliximab c. Keterolac d. Rofecoxib (b) 13. Among NSAIDs aspirin is unique because it: 13. Among NSAIDs aspirin is unique because it a. Irreversibly inhibits its target enzyme b. Reduces the risk of colon cancer c. Reduces fever d. Selectively inhibits COX-2 enzyme (a) 14. Most specific drug for the treatment of peptic ulcer caused due to chronic use of NSAIDs is : 14. Most specific drug for the treatment of peptic ulcer caused due to chronic use of NSAIDs is a. Rabeprazole b. Loxatidine c. Misoprostol d. Esomeprazole © Slide61: 15. A drug X is useful in the treatment of rheumatoid arthritis. It is available only in parenteral formulation and its mechanism of action is antagonism of tumor necrosis factor. Which of the following can be X? a. Cyclosporine b. Penicillamine c. Phenylbutazone d. Etanercept (d) 16. Which of the following increases uric acid excretion?: 16. Which of the following increases uric acid excretion? a. Allopurinol b. Aspirin c. Colchicine d. Probenecid (d) 17. True about COX-2 are all EXCEPT: 17. True about COX-2 are all EXCEPT a. Furosemide b. Sulfinpyrazone c. Allopurinol d. Piroxicam (d) 18. Allopurinol potentiates the action of: 18. Allopurinol potentiates the action of a. Corticosteroids b. Probenecid c. 6-Mercaptopurine d. Ampicillin © 19. Probenecid interacts with: 19. Probenecid interacts with a. Streptomycin b. Ampicillin c. Vancomycin d. Erythromycin (b) 20. Drug useful for gout: 20. Drug useful for gout a. Pyrazinamide b. Rifampicin c. Allopurinol d. Naloxone © 21. Loading dose of leflunomide in rheumatoid arthritis is: 21. Loading dose of leflunomide in rheumatoid arthritis is a. 20 mg b. 10 mg c. 100 mg d. 400 mg (c) Thanks: Thanks

Add a comment

Related presentations