CLINICAL PHARMACOLOGY &
PHARMACOTHERAPEUTICS

By
G.Sudheer Babu M.pharm
RHEUMATOID ARTHRITIS
CONTENTS
1. Introduction
2. Definition
3. Epidemiology
4. Etiology
5. Risk factors
6. Symptoms
7. Diagnosis
8. Pathophysio...
introduction
BONE STRUCTURE
1. It consists of a diaphysis or shaft and two
epiphysis or extremities.
2. The diaphysis is composed of ce...
MICROSCOPIC
STRUCTURE OF BONE
Large number of tube shaped
units – OSTEONS, containing a
central canal.(cc)

The central ca...
Functions of bones
1.

2.

3.
4.
5.
6.

Haemopoiesis, the
production of blood cells.
Forming the boundaries of
the cranial...
TYPES OF BONES
Bones are classified as:
1. Long bones: consist of a shaft
and two extremities
e.g. femur, tibia and fibula...
Stages of development of a bone
Synovial joint
1. It is characterised by the presence of capsule
between the articulating bones and the
capsule is lubrica...
1. This is a chronic progressive inflammatory
autoimmune disease mainly affecting synovial
joints.
2. It is more common in...
Other variant forms of RA:
1. FELTY’S SYNDROME:
It is a combination of rheumatoid arthritis along with splenomegaly &
cons...
Osteoarthritis
Type of disease degenerative
Tissue affected articular cartilage
Age of onset
late middle age
Joints affect...
EPIDEMIOLOGY
1. The prevalence rate is 1%, women are affected three to five times
as often as men.
2. It is 4 times more c...
ETIOLOGY
1.
2.
3.
4.

The exact causes of rheumatoid arthritis are unknown.
Abnormal autoimmune response.
Genetic suscepti...
RISK FACTORS

 According to National Rheumatoid Arthritis Society (NRAS), RA affects about
1.3 million Americans.
 AGE :...
Symptoms
1. Morning stiffness
2. Joint pain
3. Fatigue
4. Low grade fever
5. Loss of appetite
6. Presence of rheumatoid no...
DIAGNOSIS
1. Anti-CCP Antibody Test :
The presence of antibodies to cyclic citrullinated peptides (CCP) can identify
RA ye...
PATHOGENESIS OF RHEUMATOID ARTHRITIS
Genetic susceptibility
(MHC Class –II)

Joint deformities

Antigenic stimulation
CD4+...
PATHOGENESIS OF RHEUMATOID ARTHRITIS
1. due to antigenic exposure ( e.g. infectious agent ) CD4 T-cells , MHC class II ( H...
PANNUS FORMATION
Activation of macrophages releases
proteases , collagenase, acid
hydrolases, which causes
degradation of ...
treatment
CLASSIFICATION OF ANTIRHEUMATOID
DRUGS
A. Disease modifying antirheumatic drugs (DMARD’s):
1. Immunosuppressants: methotre...
DMARD’s
Methotrexate: (Mtx) immunosuppressant
Mechanism of action:
Mtx in RA mainly acts by inhibiting the enzyme Aminoimi...
Azathioprine : (purine antagonist)
Mechanism of action:
Azathioprine
Thiopurine methyl transferase (TPMT)

6- thioguanine ...
Cyclosporine:

Sulfasalazine:

Mechanism of action:

Mechanism of action:

It inhibits IL-1 & IL-2 production.

It is meta...
Leflunomide:
Mechanism of action Leflunomide
body
A77-1726 (act. Metabolite)
This metabolite inhibits the enzyme Dihydro o...
GOLD:
Mechanism of action:
It reduces the chemotaxis, phagocytosis , macrophage & lysosomal activity.
It prevents the join...
d- penicillamine:
 It is copper chelating agent with gold like action.
 It is having adverse effects similar to gold, he...
Biological response modifiers (BRM):
TNFα inhibitors: ( etanercept, infliximab & adalimumab)
 Mainly suppress macrophage ...
Etanercept :
Route & dose: S.C. injection 50mg weekly.
S/E: pain, redness, swelling & itching occurs at the site of infect...
Methotrexate
TREXALL
15mg tablets

Sulfasalazine
AZULFIDINE
500mg tablets
Adalimumab
surgery
OSTEOTOMY
 The knee is opened.
 A debridement (removal of damaged tissue) is performed in the joint to
eliminate the loo...
conclusion
There is no cure for rheumatoid arthritis.
Maintaining proper diet with regular medication is
the only way to a...
References
• 1. Ross & Wilson's., Anatomy & physiology
• 2. Harsh Mohan’s., Textbook of pathology
• 3. Rang and Dale’s., P...
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Rheumatoid arthitis
Upcoming SlideShare
Loading in …5
×

Rheumatoid arthitis

818 views

Published on

An overview on Rheumatoid arthritis.

Published in: Health & Medicine, Technology
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
818
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
27
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Rheumatoid arthitis

  1. 1. CLINICAL PHARMACOLOGY & PHARMACOTHERAPEUTICS By G.Sudheer Babu M.pharm
  2. 2. RHEUMATOID ARTHRITIS
  3. 3. CONTENTS 1. Introduction 2. Definition 3. Epidemiology 4. Etiology 5. Risk factors 6. Symptoms 7. Diagnosis 8. Pathophysiology 9. Treatment 10. Conclusion
  4. 4. introduction
  5. 5. BONE STRUCTURE 1. It consists of a diaphysis or shaft and two epiphysis or extremities. 2. The diaphysis is composed of central medullary canal containing yellow bone marrow. 3. Periosteum is a vascular membrane which covers the bone & it has two layers 4. The outer layer is tough and fibrous and the inner layer consists of osteoblasts and osteoclasts. 5.The epiphysis consists of cancellous or spongy bone made of red bone marrow. 6. Epiphysis also consists of articular (hyaline) cartilage.
  6. 6. MICROSCOPIC STRUCTURE OF BONE Large number of tube shaped units – OSTEONS, containing a central canal.(cc) The central canal consists of BV, nerves & each CC is linked with other CC through PERFORATING CANAL Cylindrical plates arranged around each central canal – LAMELLAE Between the lamellae string like cavities called LACUNAE are present containing an osteocyte The lacunae are interconnected by CANALICULI which allows the circulation interstitial fluid
  7. 7. Functions of bones 1. 2. 3. 4. 5. 6. Haemopoiesis, the production of blood cells. Forming the boundaries of the cranial, thoracic and pelvic cavities, protecting the organs they contain. Giving attachment to the muscles and tendons. Mineral storage, especially cal. Phosphate Allowing movements of the body. Giving particular shape to the body.
  8. 8. TYPES OF BONES Bones are classified as: 1. Long bones: consist of a shaft and two extremities e.g. femur, tibia and fibula. 2. Short bones: carpals (wrist) 3.Irregular bones: vertebrae & some skull bones. 4. Flat bones: sternum, ribs & most skull bones. 5. Sesamoid bones: patella (knee cap)
  9. 9. Stages of development of a bone
  10. 10. Synovial joint 1. It is characterised by the presence of capsule between the articulating bones and the capsule is lubricated with synovial fluid. 2. Synovial membrane forms the lining of capsule. 3. Synovial fluid is a thick sticky fluid secreted by synovial membrane into the synovial cavity. 1. it contains phagocytes which removes microbes and cellular debris. 2. acts as lubricant. 3. maintains joint stability. 4. Synovial fluid act as cushion by preventing the friction between the bones.
  11. 11. 1. This is a chronic progressive inflammatory autoimmune disease mainly affecting synovial joints. 2. It is more common in females than in males. 3. It is a systemic disorder where it affects not only joints but also other sites including the heart, blood vessels and skin. 4. Immune complexes composed of IgM activate and release cytokines (mainly TNF alpha and IL1) 5. These TNF & IL1 are chemotactic to neutrophils and secrete lysosomal enzymes which damage cartilage and erode bone, while the PG’s produced in the process cause vasodilation and causes pain.
  12. 12. Other variant forms of RA: 1. FELTY’S SYNDROME: It is a combination of rheumatoid arthritis along with splenomegaly & consequent haematologic derangements. 2. JUVENILE RA: occurs below 16 years of age characterised by acute onset of fever & pain at the site of knees & ankles.
  13. 13. Osteoarthritis Type of disease degenerative Tissue affected articular cartilage Age of onset late middle age Joints affected weight bearing areas e.g. hip, knee; often only a single joint Rheumatoid Arthritis inflammatory and autoimmune synovial membrane any age, mainly 30 to 55 years occasionally children small joints e.g. hands, feet often many joints
  14. 14. EPIDEMIOLOGY 1. The prevalence rate is 1%, women are affected three to five times as often as men. 2. It is 4 times more common in smokers than non smokers. 3. The incidence of rheumatoid arthritis is 3 cases per 10,000 population per annum.
  15. 15. ETIOLOGY 1. 2. 3. 4. The exact causes of rheumatoid arthritis are unknown. Abnormal autoimmune response. Genetic susceptibility. Environmental factors.
  16. 16. RISK FACTORS  According to National Rheumatoid Arthritis Society (NRAS), RA affects about 1.3 million Americans.  AGE : RA can occur at any age from childhood to old age, onset usually begins between the ages of 30-50.  GENDER : Women are more likely to develop RA than men.  SMOKING : Heavy long-term smoking is a very strong risk factor for RA.
  17. 17. Symptoms 1. Morning stiffness 2. Joint pain 3. Fatigue 4. Low grade fever 5. Loss of appetite 6. Presence of rheumatoid nodules 7. Myalgia and synovitis
  18. 18. DIAGNOSIS 1. Anti-CCP Antibody Test : The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. 2. C-Reactive Protein : High levels of C-reactive protein (CRP) are also indicators of active inflammation. 3. Rheumatoid Factor : In RA, antibodies that collect (anti IgG antibodies) in the synovium of the joint are known as Rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor.
  19. 19. PATHOGENESIS OF RHEUMATOID ARTHRITIS Genetic susceptibility (MHC Class –II) Joint deformities Antigenic stimulation CD4+ T- cells Destruction of bone, cartilage fibrosis, ankylosis Cytokines (TNF-α, INF-γ, IL-1) activate B-cells anti-IgG antibody activate activate Endothelial cells Macrophages release of adhesion molecules cytokines, proteases Inflammatory damage to synovium, small vessels, collagen Formation of immune complex, inflammatory cells, pannus
  20. 20. PATHOGENESIS OF RHEUMATOID ARTHRITIS 1. due to antigenic exposure ( e.g. infectious agent ) CD4 T-cells , MHC class II ( HLA-DR) cells are activated. 2. now the cytokines are activated , which results in the formation of TNF-α, interferon γ, IL-1 & IL-6. 3. these cytokines activate endothelial cells, B lymphocytes and macrophages. 4. activation of B-cells releases IgM antibody against IgG (i.e., anti- IgG); this molecule is termed as Rheumatoid Factor (RF) 5. IgG & IgM immune complexes trigger inflammatory damage to the synovium, small vessels and collagen. 6. endothelial cells stimulate adhesion molecules which stimulate the inflammatory cells. 7. activation of macrophages releases proteases which causes damage to the joint tissues leading to Pannus formation., which causes destruction of bone & cartilage
  21. 21. PANNUS FORMATION Activation of macrophages releases proteases , collagenase, acid hydrolases, which causes degradation of cartilage by the formation of Pannus The restriction in the movements of synovial joints is due to the formation of fibrous tissue a condition known as Ankylosis
  22. 22. treatment
  23. 23. CLASSIFICATION OF ANTIRHEUMATOID DRUGS A. Disease modifying antirheumatic drugs (DMARD’s): 1. Immunosuppressants: methotrexate, azathioprine, cyclosporine 2. sulfasalazine 3. chloroquine 4. Leflunomide 5. Gold compounds 6. d-penicillamine B. Biologic response modifier’s (BRM’S) : 1. TNFα inhibitors : Etanercept, Infliximab, Adalimumab 2. IL-1 antagonist : Anakinra c. Adjuvant drugs : Prednisolone & other corticosteroids.
  24. 24. DMARD’s Methotrexate: (Mtx) immunosuppressant Mechanism of action: Mtx in RA mainly acts by inhibiting the enzyme Aminoimidazole carboxamide ribonucleotide transformylase (AICAR) & thymidylate synthetase enzyme, which results in the inhibition of cytokine production. Pharmacokinetics:  Oral absorption : 70%  Half life : 6-9 hours  Excretion : urine (70%) & bile (30%) Adverse effects:  nausea and mucosal ulcers.  In some patients liver damage leading to cirrhosis.
  25. 25. Azathioprine : (purine antagonist) Mechanism of action: Azathioprine Thiopurine methyl transferase (TPMT) 6- thioguanine ( active metabolite) It acts by suppressing B-cell and T-cell function, immunoglobulin production & IL-2 secretion. Adverse effects:  Bone marrow depression  G.I disturbances  Acute allergic reactions
  26. 26. Cyclosporine: Sulfasalazine: Mechanism of action: Mechanism of action: It inhibits IL-1 & IL-2 production. It is metabolised in the body to sulfapyridine & 5-Aminosalicylic acid. Pharmacokinetics:  Bioavailability : 20-30%  Metabolism : CYP3 enzymes sulfapyridine is the active moiety which suppress the superoxide radicals and cytokine production. Adverse effects: Adverse effects:  Hypertension  Hyperkalemia  Hirsutism Reversible infertility occurs in men nausea, vomiting, headache & rashes
  27. 27. Leflunomide: Mechanism of action Leflunomide body A77-1726 (act. Metabolite) This metabolite inhibits the enzyme Dihydro orotate dehydrogenase & pyrimidine synthesis. hence there is no T-cell proliferation Pharmacokinetics: adverse effects: completely absorbed orally Half life is 19 days loss of hair leucopenia
  28. 28. GOLD: Mechanism of action: It reduces the chemotaxis, phagocytosis , macrophage & lysosomal activity. It prevents the joint destruction, may induce the healing of bony erosions. Gold is heavily bound to plasma & tissue proteins ; it stays in the body for years. It is rarely used now because it causes kidney & liver damage, bone marrow depression & hypotension
  29. 29. d- penicillamine:  It is copper chelating agent with gold like action.  It is having adverse effects similar to gold, hence its use is obsolete now. Corticosteroids:  They have immunosuppressant and anti inflammatory activity.  They are often administered with NSAIDS to have better action.  Long term use of corticosteroids causes serious adverse effects, hence low doses (5-10mg prednisolone) are used.
  30. 30. Biological response modifiers (BRM): TNFα inhibitors: ( etanercept, infliximab & adalimumab)  Mainly suppress macrophage & T-cell function.  Inflammation in the joints gradually decreases.  New bone erosions are slowed.  Quick response than DMARDS.  BRM are often combined with methotrexate for better action.  All are very expensive drugs. IL-1 antagonist: Anakinra:  it is less effective than TNFα inhibitors.  dose : 100mg S.C. daily.
  31. 31. Etanercept : Route & dose: S.C. injection 50mg weekly. S/E: pain, redness, swelling & itching occurs at the site of infection. Infliximab: Route & dose: I.V. 3-5mg is infused for every 4-8 weeks. S/E: increasing respiratory infections, worsening CHF. Adalimumab: Route & dose: S.C. injection 40mg for every 2 weeks. S/E: pain, redness, swelling & itching occurs at the site of infection.
  32. 32. Methotrexate TREXALL 15mg tablets Sulfasalazine AZULFIDINE 500mg tablets
  33. 33. Adalimumab
  34. 34. surgery
  35. 35. OSTEOTOMY  The knee is opened.  A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.  The bone is then reshaped to remove the deformity.
  36. 36. conclusion There is no cure for rheumatoid arthritis. Maintaining proper diet with regular medication is the only way to avoid the progression of the disease.
  37. 37. References • 1. Ross & Wilson's., Anatomy & physiology • 2. Harsh Mohan’s., Textbook of pathology • 3. Rang and Dale’s., Pharmacology • 4. K.D. Tripathi., Essentials of medical pharmacology

×