Pathophysiology of Rheumatoid Arthritis:

Pathophysiology of Rheumatoid Arthritis – It is an autoimmune disease that results in a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints.

It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated.

Rheumatoid arthritis (RA) is a disease in which the body’s immune system attacks its own joints.

Etiology for Rheumatoid arthritis:

Rheumatoid arthritis is a chronic systematic disease of unknown cause. An external trigger like cigarettes smoking, infections, or trauma can trigger the auto immune disorder.

It is leading to synovial hypertrophy and chronic joint inflammation alone with the potential for extra- articular manifestations, is theorized to occur in genetically susceptible individuals.

rheumatoid arthritics

Check for symptoms:

  • Systemic symptoms include early morning stiffness of affected joints,
  • Generalized afternoon fatigue and malaise
  • Anorexia (loss of appetite for food)
  • Weakness
  • Occasionally, low-grade fever.
  • Joint symptoms include pain, swelling, and stiffness.
  • Involved joints become tender, with erythematic (superficial reddening of the skin), warmth, swelling, and limitation of motion.
  • With the progression of disease, the inflammatory activity leads to erosion and distructions of joints surface with the impaired movements and leads to deformity.

Pathophysiology of Rheumatoid Arthritis – Diagnosis and Mechanism:

Clinical criteria (RA should be suspected in patients with poly-articular, symmetric arthritis, particularly if the wrists and 2nd and 3rd metacarpophalangeal joints are involved)

Serum rheumatoid factor (RF), anti-CCP(anti-cyclic citrullinated peptide antibodies), and ESR or C-reactive protein (CRP).

Rhematoid arthritis mechanism-2

Classification of anti-rheumatoid drugs:

  1. Anti-inflammatory agents
  2. Disease-modifying antirheumatic drugs (DMARDs)
  3. Biologic responce modifing Agents
  4. Janus Kinase (JAKs) Inhibitor
  5. Corticosteroids

Anti-Inflammatory Medications:

This class of drugs is also known as non-steroidal anti-inflammatory drugs (NSAIDs). They work by inhibiting and/or interfering with chemicals in the body which cause inflammation. The most common drawback to NSAID use is their propensity to cause stomach and gastrointestinal bleeding.

  • Aspirin
  • Diclofenac
  • Diclofenac/Misoprostol (Arthrotect)
  • Etodolac
  • Ibuprofen (Motrin, Advil)
  • Indomethacin (Indocin)
  • Ketoprofen
  • Naproxen (Naprosyn, Anaprox, Aleve)
  • Naproxen/Esomeprazole (Vimovo)
  • Naproxen/Lansoprazole (Prevacid NapraPAC)
  • Oxaprozin (Daypro)
  • Piroxicam (Feldene)
  • Sulindac
  • Tolmetin

Disease-modifying antirheumatic drugs (DMARDs):

DMARDs does not act as an inflammation or analgesic activity. It just suppress the inflammatory condition of RA. They actually can alter the course of the chronic disease, and help stop some of the damage from getting worse. DMARDs include the biological drugs listed above as well as non-biological drugs listed below.

Biologic Response Modifying Agents:

Biological drugs are proteins manufactured using recombinant DNA technology. They are immuno-suppressants that target and block the action of cells or chemicals that enable the immune system to cause inflammation and other symptoms of RA.

Biological agents are called disease-modifying antirheumatic drugs (DMARDs) because by suppressing components of the immune system they reduce symptoms and reverse the course of RA.

  •  Certolizumab (Cimzia)
  •  Etanercept (Enbrel)
  •  Golimumab (Simponi)
  •  Infliximab (Remicade)
  •  Rituximab (Rituxan) · Tocilizumab (Actemra)
    Tocilizumab (Actemra)

Counselling on side effects:

NSAIDs:

Aspirin is no longer used for RA, as effective doses are often toxic

NSAIDs other than coxibs should be avoided in patients with previous peptic ulcer disease or dyspepsia.

Other possible adverse effects of all NSAIDs include headache, confusion and other CNS symptoms, increased BP, worsening of hypertension, edema, and decreased platelet function.

NSAIDs increase cardiovascular risk . Creatinine levels can rise reversibly because of inhibited renal prostaglandins; less frequently, interstitial nephritis can occur.

Patients with urticaria, rhinitis, or asthma caused by aspirin can have the same problems with these other NSAIDs.

Hydroxychloroquine-Usually mild dermatitis, Myopathy,Corneal opacity (generally reversible),Occasionally irreversible retinal degeneration.

Leflunomide-Skin reactions,Hepatic dysfunction,Diarrhea

Methotrexate – Liver fibrosis (dose-related, often reversible),Nausea,Possibly bone marrow, suppression,Stomatitis,Rarely pneumonitis (potentially fatal)

Sulfasalazine-Bone marrow suppression,Gastric symptoms,Neutropenia,Hemolysis,Hepatitis.

 

COX-2 inhibitors:

They have a similar gastrointestinal risk as an NSAIDs plus a proton pump inhibitor. In the elderly there is less gastrointestinal intolerance to celecoxib than to NSAIDs alone.

There however is an increased risk of myocardial infarction with COX-2 inhibitors. Anti-ulcer medications are not recommended routinely but only in those high risk of gastrointestinal problems.

 

Glucocorticoids :

While long-term use reduces joint damage it also results in osteoporosis (a medical condition in which the bones become brittle and fragile from loss of tissue.

It is typically as a result of hormonal changes, or deficiency of calcium or vitamin D) and susceptibility to infections, and thus is not recommended.

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