RAD

Rheumatoid Arthritis:

Rheumatoid Arthritis DRUGS IN THE MANAGEMENT OF DR ANTON PRIYANTHA WARNAKULASURIYA

Rheumatoid Arthritis:

Rheumatoid Arthritis Chronic systemic inflammatory disease of unknown etiology Affects the Synovial Membranes of multiple joints Prevalence 1-2% Female : Male ratio 3:1 Usual age of onset 20-40 years

Rheumatoid Arthritis Pathological findings :

Rheumatoid Arthritis Pathological findings Chronic synovitis with pannus formation. The pannus erodes cartilage, bone, ligament and tendons. Acute phase joint effusions and other manifestations of inflammation are evident Later stages ankylosis of the joint may seen In both the acute and chronic phases, widespread inflammation of the tissues around the joint that can lead to significant joint destruction.

Rheumatoid Arthritis Pathological findings:

Rheumatoid Arthritis Pathological findings

Rheumatoid Arthritis Clinical presentation :

Rheumatoid Arthritis Clinical presentation Usually presents insidiously Malaise, weight loss and vague periarticular pain & stiffness may be seen Less commonly the onset is acute, triggered by a stressful situation such as infection, trauma, emotional strain or postpartum period. Joint involvement is characteristically symmetric with associated stiffness, warmth , pain and tenderness

Rheumatoid Arthritis Clinical Features :

Rheumatoid Arthritis Clinical Features Morning stiffness which improves during the day; its duration is a useful indicator of the activity of the disease. The stiffness may recur especially after strenuous activity Metacarpophalangeal ,PIP ,Wrists, knees ankle joints are commonly affected Entrapment syndromes may occur eg ,carpal tunnel syndrome

Rheumatoid Arthritis Joint involment:

Rheumatoid Arthritis Joint involment

Rheumatoid Arthritis Clinical Features cont..:

Rheumatoid Arthritis Clinical Features cont.. 20% of patients with RA will have subcutaneous nodules Splenomegaly andlymphadenopathy can occur sometimes Low grade fever , Anorexia, Weight loss, Fatigue and Weakness

Rheumatoid Nodules :

Rheumatoid Nodules

Rheumatoid Arthritis Clinical features cont..:

Rheumatoid Arthritis Clinical features cont.. After months to years, deformities can occur; the most common are Ulna deviation of the fingers Boutonniere deformity - hyperextension of the DIP joint and flexion of the PIP joint Swan neck deformity which is flexion of DIP joint and extension of the PIP joint Valgus deformity of the knee

Boutonniere deformity Swan neck deformity :

Boutonniere deformity Swan neck deformity

Rheumatoid Arthritis clinical features cont..:

Rheumatoid Arthritis clinical features cont.. Dryness of the eyes, mouth and other mucus membranes ,especially in advanced disease Pericarditis and pleuritis can occur but are usually clinically silent Aortitis can occur as a late complication, usually associated with vasculitis; can lead to aortic regurgitation

Rheumatoid Arthritis:

Rheumatoid Arthritis Laboratory Investigation Rheumatoid factor , an IgM antibody is seen in the sera of 75% of patients with RA High titers of rheumatoid factor are associated with severe disease. Rheumatoid factor is also found in other diseases like syphilis, sarcoidosis, infective endocarditis , Antinuclear antibody are seen in 20% of patients with RA

Rheumatoid Arthritis:

Rheumatoid Arthritis Laboratory Investigations cont. . ESR is elevated both in the acute and chronic phases of the disease Anemia is often present which is usually hypochromic normocytic white count is normal or slightly increased but leukopenia may occur, often in presence of splenomegaly (e.g., Felty’s syndrome) Platelet count is often elevated in proportion to the degree of joint inflammation

Rheumatoid Arthritis:

Rheumatoid Arthritis Labs … Joint fluid examination - The fluid is translucent to opaque and has between 3000 and 50,000 WBCs /microL. Joint fluid culture is negative. X-ray.. X-ray changes are most specific for RA . Usually are negative during the first 6 months of the disease

Rheumatoid Arthritis:

Rheumatoid Arthritis X-rays cont.. Earliest changes occur in the wrist or feet soft tissue swelling and juxta-articular demineralization. Later , diagnostic changes consisting of joint space narrowing and erosions develop. Diagnostic changes also occur in the cervical spine with C1-2 subluxation, but this can take several years to develop.

X-RAY CHANGES IN RA:

X-RAY CHANGES IN RA

Rheumatoid Arthritis Diagnosis:

Rheumatoid Arthritis Diagnosis 1987 American College of Rheumatology Revised criteria for the diagnosis of Rheumatoid Arthritis : At least four of the following Morning stiffness > 1 hour Synovitis in three joints simultaneously For 6 weeks Synovitis in wrist or hand MCP or PIP joints Symmetrical arthritis (same joint areas on both sides of the body) Rheumatoid nodules Serum rheumatoid factor Radiographic changes typical of Rheumatoid Arthritis

Rheumatoid Arthritis Management :

Rheumatoid Arthritis Management Establish the diagnosis clinically Use NSAIDs and analgesics to control symptoms Try to induce remission with IM Depot Methylpredinisolone 80-120mg if synovitis persist beyond 6 weeks IF synovitis recurs start Sulfasalazine or Methotrexate ,2 nd dose of Depot Methylprednisolone

Rheumatoid Arthritis Management cont,:

Rheumatoid Arthritis Management cont, Refer to physiotherapy If no significant improvement in 6-12 weeks consider combination of Methotrexate and Sulfasalazine If no better consider alternative agent such as Gold ,D- Penicillamine or Leflunamide If still no better , consider anti –TNF alpha therapy

Rheumatoid Arthritis Drug Treatment :

Rheumatoid Arthritis Drug Treatment NSAIDs DMARDs 1. Methotrexate 2. Sulfasalazine 3. Hydroxychloroquin 4. Gold salts 5.Penicillamine 6.leflunamide 7.Azathioprine 8.Ciclosporin Corticosteroids Tumor Necrosis factor blockers

NON STEROIDAL ANTI INFLAMMATORY DRUGS :

NON STEROIDAL ANTI INFLAMMATORY DRUGS NSAIDS Act primarily by inhibiting the cycloxygenase enzyme  that inhibit conversion of arachidonic acid to prostaglandins

NON STEROIDAL ANTI INFLAMMATORY DRUGS cont :

NON STEROIDAL ANTI INFLAMMATORY DRUGS cont Actions -Analgesia -Anti inflammatory -Antipyretic -Anti platelet Provide symptomatic relief and improve clinical indicators ,but do not improve outcome of RA Adverse effects -Gastric mucosal damage -Bleeding ,Anaphylactoid rea . -Limitation of renal blood flow

NSAIDS – ASPRIN :

NSAIDS – ASPRIN Acetyl salicylic acid Oldest and most commonly used NSAID Action –Blocks prostaglandin synthesis at hypothalamus and peripheral target -Has Analgesic ,Anti inflammatory Antipyretic effects Dose in RA -300-900mg x 4-6 h

NSAIDS –PARACETAMOL:

NSAIDS –PARACETAMOL Acetaminophen Popular domestic analgesic ,Antipyretic Action –Inhibit Prostaglandin synthesis in brain Adult dose -500-1000mg x 6 or 8 hrly Child dose -10mg/kg x 6 or 8 hrly

NSAIDS - INDOMETHACIN :

NSAIDS - INDOMETHACIN Contains Indol Potent than Asprin as an Anti inflammatory agent ,but inferior to the asprin at doses tolerated by RA patients Highly potent inhibitor of PG synthesis and suppresser of neutrophil motality Dose -25-50mg OD or BD

NSAIDS – IBUPROFEN :

NSAIDS – IBUPROFEN Contain Propionic acid Better tolerated than Asprin Action – Inhibit PG synthesis &platelet aggregation Adult dose -400-800mgxTDS Child dose -20mg/kg/day

NSAIDS –MEPHANAMIC ACID:

NSAIDS –MEPHANAMIC ACID Contain Fenamate Actions – Inhibit PG synthesis -Antagonizes action of PG -Has Analgesic ,Anti inflammatory Antipyretic effects Dose - 250-500mg TDS

NSAIDS – DICLOFENAC SODIUM:

NSAIDS – DICLOFENAC SODIUM Contain –Phenylacetic acid Action –Inhibit PG synthesis -Has Analgesic ,Anti inflammatory Antipyretic effects It achieves high synovial concentration Dose – 100-150mg/2-3 divided doses

NSAIDS – PIROXICAM:

NSAIDS – PIROXICAM Contain –Oxicam Long acting potent NSAIDS Action –Lower PG concentration in synovial fluid -Decrease production of RF Anti inflammatory potency similar to Indomethacin Dose in RA –Initially 20mg daily Maintenance 1o-30mg daily

DISEASE MODIFYING ANTI RHEUMATIC DRUGS (DMARDS):

DISEASE MODIFYING ANTI RHEUMATIC DRUGS (DMARDS) These Agents can suppress the immune process in RA They reduce joint pain , swelling , stiffness and long term joint damage Mechanism of action is not understood well ,But some actions are known Methotrexate Anti folate drugs Sulphasalazine Ciclosporin Affects T cell function Drugs differ in their speed of onset of action takes weeks to months Require bridging therapy with NSAIDS or Corticosteroids

DISEASE MODIFYING ANTI RHEUMATIC DRUGS (DMARDS):

DISEASE MODIFYING ANTI RHEUMATIC DRUGS (DMARDS) As all affect immune system regular monitoring is required eg. Liver ,Kidney ,Bone marrow status As general rule patients receiving DMARDS should not be given live vaccines DMARDS during pregnancy and lactation is contraindicated

DMARDs-Methotrexate :

DMARDs- Methotrexate Inhibit dihydrofolate reductase

DMARDs-Methotrexate :

DMARDs- Methotrexate considered by many to be the drug of choice for RA. It produces a beneficial effect in 2-6 weeks and is given once weekly. The usual dose is 7.5-15 mg once a week SI- Mouth ulcers , Gastric irritation , stomatitis, hepatotoxicity, pancytopenia a, interstitial pneumonitis. Oral Folic acid is given to reduce side effects

Methotrexate SI – Mouth ulcers:

Methotrexate SI – Mouth ulcers

DMARDs- Sulfasalazine :

DMARDs- Sulfasalazine Combination of sulfapyradine and 5 amino salicylic acid Has antifolate action Sulfasalazine is a good second line agent for rheumatoid arthritis with an efficacy similar to gold and penicillamine. Dose -500mg daily after food SI – nausea ,skin rashes ,mouth ulcers neutropenia and thrombocytopenia.

DMARDs-GOLD SALTS (Sodiumaurothiomalate):

DMARDs-GOLD SALTS (Sodiumaurothiomalate) Most effective agent for arresting rheumatoid process and prevent involment of additional joints Action – Modify cellular and humoral immune response Indications are limited by their many side effects. Gold salts are used, especially in cases where patients are not responding to Methotrexate or in case of severe erosive disease. Test dose of 10mg im followed by weekly 50mg SI-skin rashes ,mouth ulcers ,pancytopenia ,renal impairment

DMARDs- HYDROXYCHLOROQUIN :

DMARDs- HYDROXYCHLOROQUIN Effective in 25-50% of patients and in most cases after 3-6 months of therapy. It is reserved for mild disease. Anti inflammatory and immunomodulatory effects are useful in RA Less effective but less toxic Dose 200-400mg daily SI-skin rashes ,corneal deposits ,retinal damage Test visual fields at 6 months

DMARDs- D-Penicillamine:

DMARDs- D-Penicillamine Analogue of amino acid cysteine Action is unclear in RA , But act as a chelating agent Slows the progress of bone destruction Reduces RF in serum Dose -125mg daily then 250mg xbd SI-nausea ,loss of taste ,skin rashes , mouth ulcers,pancytopenia ,renal impairment

DMARDs- Leflunomide :

DMARDs- Leflunomide Inhibits pyrimidine synthesis and prevent T cell proliferation Onset of action is faster than other DMARDs Dose -100mg daily x3 days then 20mg daily SI-GI upset,pancytopenia ,hepatotoxity alopecia ,hypertension

DMARDs- CICLOSPORIN:

DMARDs- CICLOSPORIN Is a Polypeptide obtained from a soli fungus Inhibit production of lymphokines by T-lymphocytes It is used to prevent and treat in rejection in organ transplants and bone marrow transplants Has been tried in patients with RA Still under research

CORTICOSTEROIDS:

CORTICOSTEROIDS Has potent immunosuppressant and anti inflammatory activity Can introduce at any stage of RA Powerful disease controlling drugs Avoided in long term because of side effects Dose -Maintaince therapy Prednisolone 5 -7.5mg PO /OD In Extreme severity 20-40mg PO/OD -IM /IV/intra articular injections Methylprednisolone 40-120mg SI-Cushing like syndrome,HT,DM,Osteoporosis &necrosis cataracts ,glucoma ,peptic ulcer, reduction of immunity

Tumor Necrosis factor blockers INFIXIMAB:

Tumor Necrosis factor blockers INFIXIMAB Inhibit TNF alfa by binding to it in the circulation or joint cavity Reserved for patients with severe RA Used in combination with Methotrexate Dose -2mg/kg iv infusion at day 0,6,8 and weekly SI-Infection ,fever ,headache vertigo,hypertension ,skin rashes ,ccf GI upset

ETANERCEPT:

ETANERCEPT Inhibits the activity of Cytokine and TNF Reserved for patients with active RA failed to respond to other DMARDs Dose – 25mg s/c x twice a week SI –Injection site reaction ,Infection , headache abdominal pain ,malignancies Cholecystitis

SUMMARY OF DRUG TREATMENT IN RA:

SUMMARY OF DRUG TREATMENT IN RA Pre Diagnosis Analgesics NSAIDs Intra articular corticosteroids Diagnosis made DMARDs Corticosteroid birding NSAIDs Established disease DMARDs Change DMARDs if SI Combine DMARDs if inadequate Withdraw NSAIDs if possible Corticosteroid PO/Intra articular dis.flares

MCQ:

MCQ 01.Which DMARD is the drug of 1 st choice in RA a. Sulfasalazine b.Antimalarials c.D-Penicillamine d. Methotrexate 02.Which of the following is not a DMARD used for RA a.Gold compounds b.D-Penicillamine c.Infleximab d.Antimalarials 03.Which of the following is not an a immunosuppressive drug which is used in RA a.Azathioprime b.Leflunomide c.Cyclosporine d.D.Penicillamine

REFERENCES:

REFERENCES Apleys system of orthopaedics and fractures Clinical pharmacology –P.N .Bennet Clinical Medicine –Kumar & clerk Review of orthopaedics –Miller Jaypees Review of Orthopaedics

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