Rheumatoid Arthritis& gout

Rheumatoid arthritis & Gout: 

Submitted By :- S uryakant Patel Department of pharmacology Rheumatoid arthritis & Gout 1

Rheumatoid Arthritis: 

(RA) is an autoimmune disease that causes chronic inflammation of the joints & can also cause inflammation of the tissue around the joints, as well as in other organs in the body. Multisystem disease Inflammatory arthritis Peak incidence in 3rd to 4th decades of life 3-5 times higher preponderance in females than males Rheumatoid Arthritis 2

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Etiopathogenesis: 

Exact mechanism is not known 1 ) Autoantibody-Rheumatoid factor(R.F.) R.f. is Anti-IgG 80% of cases happens due to R.F. so it is widely accepted 2 )other autoantibodies: Antinuclear factor(ANF) Antibodies to Collagen type-2 class Antibodies to cytoskeleton Etiopathogenesis 4

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Activation of cell-mediated immunity which is observed by numerous inflammatory cells E.g. CD4+ T-lymphocytes & some macrophages 4 )Trigger events :- Local/systemic infection It includes some infectius agents such as Epstein-Barr Virus(EBV) cytomegalovirus(CMV) rubella 5

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Epidemiology: 

In a region 3/10,000 per annum Uncommon in below 15 age In ages of 60-80 it is maximum Degree of relative prevalence rate is 2-3% Epidemiology 7

Signs & symptoms: 

Tender , warm , swollen joints Symmetric pattern of affected joints Joints inflammation often affect wrist & finger joints Also affect other joints including neck ,shoulder ,elbow ,hips ,knees ,ankles ,feet Fatigue ,occasional fever ,sense of not feeling well Pain & stiffness after morning wake up or after a long rest Signs & symptoms 8

Diagnosis: 

By imaging: -X-ray -MRI -Ultra sound By Blood tests: a)Inflammatory markers: -ESR(erythrocytes sedimentation rate) -C reactive protein(CRP) -ANA(anti-nuclear antibody) Diagnosis 9

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b)Rheumatoid factor: c)Anti-ccp antibodies d)Anti-MCV assay b)Rheumatoid factor : In 75-80%,gives +ve result Low sensitivity ,bcoz it gives +ve result in some other diseases like hepatitis,sjogren’s syndrome c)Anti-ccp antibodies:it in 99% gives +ve result Specificity is 95%. Modification:Anti-MCV assay (anti-Mutated citrullinated Vimentin) Sensitivity-72% Specificity-99.7% 10

TREATMENTS: 

There is no cure for RA,there is some treatments which can modify the disease process. GOAL for Treatments : Relieve pain Reduce inflammation s low down or stop joint damage TREATMENTS 11

Current treatment approaches: 

1)medication 2)surgery 3)lifestyle 1)medication: Classification: a) Anti-inflammatory-analgesic drugs b) Anti-inflammatory drugs without direct analgesic action Current treatment approaches 12

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c)Disease Modifying Antirheumatic Drugs(DMRDs) d)immunosuppressants e)TNF-alpha blockers f)Interleukin-1 blockers ANTIINFLAMMATORY-ANALGESIC DRUGS Eg.aspirin,indomethacin,ibuprofen,naproxen, piroxicam,nabumetone,diclofenac,celecoxib M.O.A: It inhibit pg,& chemicals that are responsible for pain and swelling 13

figure: 

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Adverse effect: Stomach upset(not in selective cox-2 inhibitors) Increase risk of heart attack,stroke & related conditions It is the one of the risk factor for heart disease DOSE: Aspirin-500-1000 mg every 6 hours or BD. Heart attacks are prevented with 50/75 or 325 mg daily Indomehacine-:50-200 mg per day split into 2-3 doses 15

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Ibuprofen-: 200 or 400 mg every 6 hours. Individuals should not use ibuprofen for more than 10 days for the treatment of pain or more than 3 days for the treatment of a fever unless directed by a physician 250-500 mg twice daily 20 mg once daily or 10 mg twice daily 1000 mg daily as a single dose. Some patients may respond better to 1500 or 2000 mg daily. The lowest effective dose should be used 50-100 mg /day 16

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Celecoxib:100 or 200 mg twice daily. The lowest effective dose should be used for each patient GLUCOCORTICOIDS-:They are used when disease Is not responding NSAIDs. Have serious side effect incase of high doses Eg.prednisolone:- 5-10mg daily M.O.A:- 17

ADVERSE EFFECT: 

Weight gain Facial puffiness Thinning of skin & bones Risk of infection Muscle wasting Distruction of joints such as hips ADVERSE EFFECT 18

Remission inducing drugs DMARDs: 

Eg. Methotrexate Hydroxychloroquine Sulfasalazine Gold salts METHOTREXATE: It is antimetabolite drug. Dose:- 7.5 mg/weekly Remission inducing drugs DMARDs 19

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M.O.A:-It inhibit dihydro folate Reductase enzyme. Adverse effect:- It comes in x-category drugs Teratogenecity Osteoporosis Stomatitis Myelosuppression Decrease W.B.C. count 20

OH-chloroquine: 

It is antimalerial drug. M.O.A.:- DOSE:400-600mg daily for 4-12 weeks followed by 200-400mg daily Adverse effects:- Without food cause stomach upset Abdominal cramps Decrease appetite Mild diarrhea OH-chloroquine 21

sulfasalazine: 

Sulfasalazine is used to treat rheumatoid arthritis in combination with anti- inflammatory medications. Sulfasalazine is generally well tolerated. Adverse effects:- Stomach upset Should be avoided by sulfa allergic patient b’coz it is made up of sulfa & salicylate compounds. sulfasalazine 22

Gold salts: 

Eg. Gold thioglucose(SOLGANAL) G old thiomalate (MYOCHRYSINE ) Auranofin ( RIDAURA) Adverse effect:- skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white cell count. Patients receiving gold treatment are regularly monitored with blood and urine tests. Oral gold can cause diarrhea. Gold salts 23

Combination therapy: 

MTX + SSZ + OH-Chloroquine MTX + CSA MTX + Etanercept MTX + Remicade MTX + Adalimumab MTX + Leflunomide excellent safety & improved efficacy over MTX alone Combination therapy 24

Joint replacement: 

25 Joint replacement Hip replacement Knee replacement SYNOVECTOMY

GOUT: 

It is metabolic disorder characterized by hyperuricaemia Normal plasma=1-5 mg/dl Stages of gout:- 1)asymptomatic hyperuricaemia 2)acute gouty arthritis 3)intercritical period 4)chronic tophaceous stage GOUT 26

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Types :- 1)metabolic- 10% cases Over production of uric acid 2)renal- 90% cases Reduced renal excretion of uric acid Causes:- 1)genetic(absence of hypoxanthine) 2)medication:- 3)lifestyle 27

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Drugs that causes hyperuricaemia : Alcohol Thiazide Cytotoxic drugs Amiloride Isoretinoin Ethambutol Cyclophosphamide 28

Sign & symptoms : 

Acute attack: Over hours frequently nocturnal Excruciating pain Swelling, redness and tenderness Podagra May effect knees, wrist, elbow, and rarely SI and hips Chronic: Destructive tophacous Much greater chance if untreated nodules Sign & symptoms 29

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Renal lithiasis Uric acid nephropathy Urate nephropathy DIAGNOSIS:- X-ray Synovial fluid test:- Sample of S.F. is obtained and examined for crystals. Blood test:- Normal level:1-5mg/dl Above 7 in males Above 6 in females indicate hyperuricaemia. W.B.C.,ESR is increased in gout without infection. 30

Pathogenesis : 

Uric acid is end product of purine metabolism Monosodium urate has low water solubility When conc. Of MSU is above 7mg/dl,their solubility is decreased due to saturation and it form crystal. Pathogenesis 31

Treatment : 

Goal of treatment:- Relieve pain Reduce inflammation Terminate acute attack Prevent recurrent attack Prevent complications associated with chronic deposition of urate crysals in tissues. Treatment 32

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Classification of drugs: 1)NSAIDs 2)colchicine 3)corticosteroids 4)uricosuric drugs 5)xanthine oxidase inhibitor NSAIDs:- Indomethacin Naproxen Piroxicam diclofenac Mainly indomethacin is used.bcoz it is less toxic than others. Dose-25-50mg tid for 5-7 days. 33

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Adverse effect- Stomach upset (not in selective cox-2 inhibitors) Increase risk of heart attack , stroke & related conditions It is the one of the risk factor for heart disease. COLCHICINE:- It is an alkaloid from colchicum autumnale. It is antimitotic drug. 34

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MOA-it inhibit release of Glycoprotein & subsequent Events. It inhibit granulocyte Migration into inflamed joints. DOSE:- 1 mg orally followed by 0.25 Mg/day. Adverse effect:- Diarrhea Abdominal cramps Kidney damage CNS depression Intestinal bleeding Nausea , vomiting 35

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CORTICOSTEROIDS:- Eg.prednisolone Dose:40-60mg/day They are rarely used.they are used in case of patient which is contraindicate to NSAIDs. they produce rapid response like colchicine.but it is contraindicated to patients with renal failure. PROBENECID:- It is uricosuric drug. MOA- It is act by inhibiting reabsorption of uric acid.so,excretion of uric acid is increased. 36

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D ose-:0.25-0.50g Adverse effects:- Dispepsia is most common side effect. On toxic doses, it can cause convulsion & respiratory failure. XANTHIN OXIDASE INHIBITOR:- Eg.allopurinol. It is hypoxanthine analogue. MOA:- It is act by inhibiting Xanthine oxidase which is required for synthesis of uric acid. DOSE:- 100mg-600mg/day. 37

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Adverse effect:- Hypersensitivity reaction like rash,fever,malasia Muscle pain Risk of stevens-johnson syndrome Gastric irritation Headache, nausea, dizziness etc. 38

Reference : 

Essential of Mediacal Pharmacology,kd tripathi Lippincott's Illustrated Reviews Pharmacology Pharmacology & pharmacotherapeuics ,RS satoskar Textbook of pathology,Harshmohan Principles of anatomy and physiology,GJ.tortora Wikipedia www.emedicinehealth.com 39 Reference