dr.b.v.venkataraman professor in pharmacology international medical school faculti perubatan, new...
DESCRIPTION
What is rheumatoid arthritis? It is an auto immune disease Affects the lining of the joints, causing pain, swelling, and stiffness. Left untreated, joints may be damaged badly Most common in young-adult to middle-age women.TRANSCRIPT
Dr.B.V.VenkataramanProfessor in Pharmacology
International Medical SchoolFaculti Perubatan, New BEL Rd
Bangalore - [email protected]
Drugs Used in Arthritis
Immune SystemImmune SystemImmune System
Foreign bodies Foreign bodies Own cells
Eradicated Failed
No infection Infection
Auto immuneDiseases
What is rheumatoid arthritis?
It is an auto immune disease Affects the lining of the joints, causing pain, swelling, and stiffness. Left untreated, joints may be damaged badly Most common in young-adult to middle-age women.
What is osteoarthritis?Osteoarthritis results from wear and tear on the joints.
What are the drugs used in RA?
1. Anti inflammatory drugs: NSAIDs
2. Corticosteroids: Prednisolone
3. Disease modifying antirheumatic drug(DMARDS)
Non biologic Biologic
DMARDS (Non biologic)
Target immune cells usually by unknown mechanisma. Immunosuppressants:
Methotrexate, leflunomide, azathioprine, cyclosporine etc
b. Antimalarials: Hydroxy Chloroquine
c. Gold salts: aurothiomalate, aurothioglucose
d. MiscellaneousSulphasalazine
DMARDS (biologic)
Target specific parts of inflammatory cascadeSpecificExamples:Anakinra, inflixima,TNFα inhibitors and IL-1 antagonist etc.
What is the mechanism of action of NSAIDS?
MechanismInhibit the synthesis of prostaglandins and reduce cause of pain and inflammation. Main drugsDiclofenac, ibuprofen, indomethacin, piroxicam etc.Long term side effects Allergy, peptic ulcer, bleeding disorders, renal function impairment etc.
What is the mechanism of action of NSAIDs?
NSAIDs
Interactions
Bleeding tendency with oral anticoagulantsFluid retention decreases the efficacy of diuretics and antihypertensives.Protein binding increases the risk by displacement principle
COX-2 INHIBITORSLess gastric irritation No anti platelet action; no protection against heart attack or stroke
How does corticosteroid act on inflammation?
Steroids
Glucocorticoid
How does corticosteroid
act on immunity?
Corticosteroids
Prednisone, methyl prednisolone and hydrocortisoneInflammation, suppress the immunitySide effects: bone loss, weight gain, acne, high blood pressure, mood swings, and infection Topical. Intra articular administration also possible
DMARDS (Non biologic)
Heterogenous class without common propertySymptomatic improvementSlow progressMost of them were developed for other disorder – cancer, immunosuppressionToxicity and inadequate response limit the useCombined with biologic DMARDs
METHOTREXATE
Inhibition of folic metabolism – for anti cancer activityProposed Mechanism:Inhibit T-cell proliferation to inhibit transmethylation reactions required for T-cell cytotoxicityto promote the release of adenosine, an endogenous anti-inflammatory mediatorto interfere with glutathione metabolism, and alter the recruitment of monocytes to the inflamed joint
AzathioprineMethotrexate
Mechanism of immunosuppressants drugs
METHOTREXATE (Contd)
Useful in patients refractory to other drugsGiven with folic or folinic acid (Leucovorin) to decrease mouth ulcer, anaemia etcLiver function testLow dose (not anticancer dose) given weekly
LEFLUNOMIDE
Alternative to MethotrexateGiven to patients who can not tolerate methotrexateInhibits dihydro orotate dehydrogenase (dihydro folatereductase) – anticancer activity Inhibit proliferation (similar to methotrexate)Dose is daily (methotrexate weekly)Liver function test
Hydroxy chloroquine
Interfering with tumor necrosis factor (TNF) released from macrophages, or Diminishing the presentation of antigens to CD4+ T cells. Slow progress – used in mild diseaseWell toleratedRetinal toxicity – ophthalmic examination required
Sulfasalazine (Salicylazosulfapyridine)
Sulfasalazine
5-Aminosalicylic acid Sulfapyridine
Coliform bacteria
Local antiinflammatory
Immunomodulating
Systemic side effect
(Carrier)
Mechanism not clear; also used in other auto immune conditions
Not used in sulpha sensitivity
MESALAMINE
MESALAMINE
5-Aminosalicylic acid
Coliform bacteria
Local antiinflammatory
Immunomodulating
No systemic effect
(Carrier)Ethylcellulose/pH
sensitive resin
GOLD SALTS
Organic complexes: sodium aurothiomalate, auranolin.Mechanism: poorly understoodVery slow progressOral & parenteral preparations availableToxic symptoms:Proteinuria, thrombocytopenia, and neutropenia – decreased WBCs and kidney damage
ANTI-TNF AGENTS
InfliximabAdalimumabEtanercept All useful in mild to moderate RAInfliximab (iv) other two (sc)Risk of infection such as tuberculosisRisk of Malignancy
MechanismAnti-TNF monoclonal antibody
Binds to TNF- TNF- fails to bind to receptor cell surfaceSide effectsbreathlessness, hypotension, headache.
INFLIXIMAB
ADALIMUMAB
Mechanism Similar to Infliximab
ETANERCEPTMechanismfusion protein composed of 2 recombinant soluble TNF receptors binds to TNF-α, and lymphotoxin-α
ANAKINRA
Interleukin-1βDecrease WBC count, risk of infection (TB) and malignancy - similar to anti-TNF agent.Dramatic relief similar to anti-TNF agent.