The Rheumatoid arthritis & its drugs treatments .

1. RHEUMATOID ARTHRITIS
GUIDED BY:
MR. JAGAT UPADHYAY
ASST. PROFESSOR PHARMACEUTICAL CHEMISTRY
PREPARED BY:
HARSH CHUNARA
ID NO: 10P008
ROLL NO: 08
YEAR : 4th year
FACULTY OF PHARMACY DHARMSINH DESAI UNIVERSITY, NADIAD.

2. CONTENT
 Introduction
 Signs and symptoms
 Epidemiology Rheumatoid arthritis
 Etiology of Rheumatoid arthritis
 Drugs used in Rheumatoid arthritis
 Mechanism of action
 Treatment of Rheumatoid arthritis
 References
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4. What Is Rheumatiod Arthritis ?
 RA, is a form of inflammatory arthritis and an autoimmune disease
 The immune system – is designed to protect our health by attacking foreign cells
such as viruses and bacteria – instead attacks the body’s own tissues, specifically
the synovium, a thin membrane that lines the joints. As a result of the attack, fluid
builds up in the joints, causing pain in the joints and inflamation that’s systemic –
meaning it can occur throughput body.

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6. Sign & symptoms
 joints may feel warm to the touch and decreased range of motion, as well as
inflammation,
 swelling and pain in the areas around the affected joints.
 Stiffness
 Malaises(feeling ill)
 Muscle aches
 Loss of appetite, which can lead to weight loss
 pain
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8. Epidemiology
 More than 21% of American adults (over 46 million people) have arthritis or
another rheumatic condition diagnosed by a doctor.
 Nearly two-thirds of arthritis patients are under 65 years old.
 More than 60% of arthritis patients are women.
 By 2030, the number of people with arthritis is expected to rise to 67 million,
reflecting a 40% increase.
 RA Although it can occur at any age, the peak onset period is between the ages of 35 and
50. The disease may come on slowly or may appear suddenly.
 The average age for being diagnosed with rheumatoid arthritis has steadily
increased (from 63.3 to 66.8 years old), suggesting rheumatoid arthritis is becoming a
disease of older adults.
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9. Etiology
 Even though infectious agents such as viruses, bacteria, and fungi have long been
suspected as well as smoking, but none has been proven as the cause. It is believed
that the tendency to develop rheumatoid arthritis may be genetically inherited.
 Eg. the genetic marker HLA-DR4 has been identified in as many as 66% of patients
with disease. This marker, which is present in white blood cells, plays a role in
helping the immune system to distinguish between foreign cells (e.g., germs) and
the body's own cells.
 RA often is affected by pregnancy—symptoms improve before the infant is born
and then worsen after delivery—it may be that hormones in the body influence
disease development and progression.
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10. Drugs used in Rheumatoid arthritis.
 NSAIDs: (Nonsteroidal anti-inflammatorydrugs)
 NSAIDs include such drugs as ibuprofen, ketoprofen ,and naproxen sodium,celecoxib.
 Ibuprofen ketoprofen
 The primary mechanism of action is inhibition of an enzyme called cyclooxygenase
(COX). COX is an enzyme that is required in the conversion of arachidonic acid to
prostaglandin H2 (PGH2) in the body.
 The prostaglandins that are formed from PGH2 are important mediators of sensations
such as pain and processes such as fever and inflammation.
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11.  ibuprofen is a non-selective COX inhibitor. There are two forms of COX in the body - COX-
1,2.
 The pain and inflammation reducing effects of NSAIDs are mediated through the inhibition
COX-2, & COX-1 inhibition blocks the formation of thromboxane. The long-term blockage of
COX-1 with chronic use of NSAID, however, may cause gastric toxicity, as COX-1 usually
maintains the gastric mucosa
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12.  Disease-Modifying Antirheumatic drugs(DMARDs)
 hydroxycholorquine,sulfasalazine,leflunomide.
 Methotrexate also
 M/A SULFASALASINE
 The mode of action of Sulfasalazine or 5-aminosalicylic acid (5-ASA) and
sulfapyridine
 In ulcerative colitis, clinical studies utilizing rectal administration of Sulfasalazine,SP
and 5-ASA have indicated that the major therapeutic action may reside in the 5-
ASA moiety.
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13.  Corticosteroids –
 prednisone, prednisolone and methyprednisolone,
 M/A:
 Prednisone is a glucocorticoid receptor agonist. It is first metabolized in the liver to
its active form, prednisolone. Prednisolone crosses cell membranes and binds with
high affinity to specific cytoplasmic receptors.
 the result includes inhibition of leukocyte infiltration at the site of inflammation,
interference in the function of mediators of inflammatory response, suppression of
humoral immune responses, and reduction in edema or scar tissue.
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14. Biologic agents:
 There are currently nine such agents approved for rheumatoid arthritis: abatacept ,
adalimumab , anakinra , certolizumab ,pegol etanercept , infliximab , golimumab and
rituximab .
 Each of the biologics blocks a specific step in the inflammation process. Cimzia, Enbrel,
Humira, Remicade and Simponi block a cytokine called tumor necrosis factor-alpha (TNF),
rituxan blocks b cells and therefore often are called TNF inhibitors.
rituximab
 M/A:Rituximab binds specifically to the antigen CD20 (human B-lymphocyte-restricted
differentiation antigen, a hydrophobic transmembrane protein with a molecular weight of
approximately 35 kD located on pre-B and mature B lymphocytes.
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15.  CD20 regulates an early step(s) in the activation process for cell cycle initiation and
differentiation, and possibly functions as a calcium ion channel.
 CD20 is not shed from the cell surface and does not internalize upon antibody binding. Free
CD20 antigen is not found in the circulation.
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16.  JAK inhibitors: tofacitinib
 M/A:It is an inhibitor of the enzyme janus kinase 3 (JAK3), which means that it
interferes with the JAK-STAT signaling pathway, which transmits extracellular
information into the cell nucleus, influencing DNA transcription
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17. What is actual pathophysiology of RA?
 Preclinical phase
 Several cell types and cytokines are involved in RA, and upregulation of cytokines, cytokine-related
factors, and chemokines can pre-date the development of clinical symptoms.
 Anti-citrullinated protein antibodies (ACPAs), which include include perinuclear factor (APF),
antikeratin antibodies (AKA), anti-Sa antibodies, and anticyclic citrullinated peptide antibodies
(anti-CCP), are sensitive and specific serological markers of RA, offering predictive value for a
diagnosis of RA
 Clinical phase
 The macrophages are activated by Th1 cytokines, including interferong (IFN-g), interleukin 12
(IL-12), and IL-18, which are released following activation of T cells by antigen-presenting cells.
Macrophages may also be activated by direct contact with T cells, or by immune complexes or
bacterial products in the synovial fluidsOnce activated, macrophages release multiple cytokines
and other inflammatory mediators. Key cytokines involved in the pathogenesis of RA include
several interleukins, tumor necrosis factor (TNF), transforming growth factor-β (TGF-β), &
interferons (IFNα and IFNβ). Each cytokine may have multiple pleiotropic actions, but in patients
with RA, the balance swings in favour of the proinflammatory cytokines.
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18. Cytokines play key roles in controlling cell growth and the immune response. Many cytokines
function by binding to and activating type I and type II cytokine receptors. These receptors in turn
rely on the Janus kinase (JAK) family of enzymes for signal transduction. Hence drugs that inhibit
the activity of these Janus kinases block cytokine signaling.
More specifically, Janus kinases phosphorylate activated cytokine receptors. These phosphorylated
receptor in turn recruit STAT transcription factors which modulate gene transcription.
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21. Therapy of Rheumatoid arthritis
 Corticosteroid Therapy medications can be given orally or injected directly into tissues and
joints. They are more potent than NSAIDs in reducing inflammation and in restoring joint
mobility and function.
 for short periods during severe flares of disease activity or when the disease is not
responding to NSAIDs. However, corticosteroids can have serious side effects, especially
when given in high doses for long periods of time.
 Corticosteroid Therapy These side effects include weight gain, facial puffiness, thinning of
the skin and bone, easy bruising, cataracts, risk of infection, muscle wasting, and destruction
of large joints, such as the hips.
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22. Diagnosis;
 Corticosteroid Therapy medications can be given orally or injected directly into tissues and
joints. They are more potent than NSAIDs in reducing inflammation and in restoring joint
mobility and function.
 These side effects include weight gain, facial puffiness, thinning of the skin and bone, easy
bruising, cataracts, risk of infection, muscle wasting, and destruction of large joints, such as
the hips.
 Diagnosis of RA depends on the symptoms and results of a physical exam, such as warmth,
swelling and pain in the joints. Some blood tests also can help confirm RA. Telltale signs
include:
 Anemia (a low red blood cell count)
 Rheumatoid factor (an antibody, or blood protein, found in about 80% of patients with RA in
time, but in as few as 30% at the start of arthritis)
 Antibodies to cyclic citrullinated peptides (pieces of proteins), or anti-CCP for short (found in
60–70% of patients with RA)
 Elevated erythrocyte sedimentation rate (a blood test that, in most patients with RA, confirms
the amount of inflammation in the joints)
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23.  X-rays can help in detecting RA, but may not show anything abnormal in early arthritis. Even
so, these first X-rays may be useful later to show if the disease is progressing. Often, MRI and
ultrasound scanning are done to help judge the severity of RA.
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24. Reference:
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27. ……………..Thank u……………
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