clinical pharmacy

1. Rheumatoid Arthritis

2. • Epidemiology
• Pathophysiology and clinical presentation
• Treatment
• Evaluation of treatment
• Clinical case

3. Epidemiology

4.  The prevalence estimated to be between 1% and 2% ,
with women affected 3 times more often than men
 Rheumatoid arthritis can occur at any age and often
occurs in younger people.
 Rheumatoid arthritis is an autoimmune disease with a
strong genetic predisposition.

5. Pathophysiology and clinical
presentation

6. Chronic inflammation of the synovial tissue lining the
joint capsule results in the proliferation of this tissue.
The inflamed proliferating synovium characteristic of
rheumatoid arthritis Is called pannus.
This panes invades the cartilage and eventually the
bone surface, producing erosions of bone and cartilage and
leading to destruction of the joint.
The factors that initiate the inflammatory process are unknown

10. The immune system is a
complex network of checks
and balances
designed to discriminate
self from non-self (foreign)
tissues.
It helps rid the body of
infectious agents, tumor
cells, and products
associated with the
breakdown of cells.
In rheumatoid arthritis, this
system no longer can
differentiate self from non-
self tissues and attacks the
synovial tissue and other
connective tissues

12. The immune system has both
humeral and cell-mediated
functions.
The humeral component is
necessary for the
formation of antibodies. These
antibodies are produced by
plasma
cells, which are derived from B
lymphocytes.
Most patientswith rheumatoid
arthritis form antibodies called
rheumatoid factors

13. Symptoms
■Joint pain and stiffness of more than 6 weeks’ duration
May also experience fatigue, weakness, low-grade fever,
Loss of appetite. Muscle pain and afternoon fatigue may also be
present.
Joint deformity is generally seen late in the disease.
Signs
■Tenderness with warmth and swelling over affected joints
usually involving hands and feet. Distribution of joint involvement
is frequently symmetrical. Rheumatoid nodules may also be
present

14. Laboratory Tests
■Rheumatoid factor (RF) detectable in 60% to 70%.
■Ant cyclic citrullinated peptide (anti-CCP) antibodieshave
similar sensitivity to RF (50% to 85%) but are morespecific
(90% to 95%) and are present earlier in the disease.
■Elevated erythrocyte sedimentation rate and C-reactive
protein are markers for inflammation.
■Normocytic normochromic anemia is common as is
thrombocytosis.

15. Other Diagnostic Tests
■Joint fluid aspiration may show
increased white blood cell
counts without infection, crystals.
■Joint radiographs may show
periarticular osteoporosis, joint
space narrowing, or erosions

16. EXTRAARTICULAR INVOLVEMENT
Rheumatoid Nodules
Vasculitis
Pulmonary Complications
Ocular Manifestations
Felty’s Syndrome
cardiac Involvement
Other Complications

17. LABORATORY FINDINGS
Normocytic normochromic anemia
Thrombocytosis
Leucopenia
ESR is elevated
C-reactive protein elevated
RF present in 60-70 % of patient
Anti- CCP antibody in 50-85%
Antinuclear antibodies in 25%

18. Diseases Associated with a
Positive
Rheumatoid Factor
Rheumatic diseases
Rheumatoid arthritis
Sjögren’s syndrome (with or without
arthritis)
Systemic lupus erythematosus
Progressive systemic sclerosis
Polymyositis/dermatomyositis
Infectious diseases
Bacterial endocarditis
Tuberculosis
Syphilis
Infectious mononucleosis
Infectious hepatitis
Leprosy
Other causes
Aging
Interstitial pulmonary fibrosis
Cirrhosis of the liver
Chronic active hepatitis
Sarcoidosis

19. TREATMENT

20. DESIRED OUTCOME
Control of inflammation is the key to slowing
or preventing disease progression as well
as managing symptoms

21. a. Reduction in the number of affected joints
and in joint tenderness and swelling
b. Improvement in pain
c. Decreased amount of morning stiffness
d. reduction in serological markers such as RF
e. Improvement in quality-of-life scales

22. NONPHARMACOLOGIC THERAPY
a. Rest during periods of disease exacerbation
b. Occupational and physical therapy to support
mobility and maintain function
c. Maintenance of normal weight to reduce
biomechanical stress on joints
d. Surgery (Tenosynovectomy, tendon repair,
And joint replacements).
e. Smoking Cessation

23. PHARMACOLOGIC THERAPY
Drug therapy should be only part of a
comprehensive program for patient management
which would also Include physical therapy,
exercise, and rest.
surgery may beAssistive devices and orthopedic
necessary in some patients

24. There are four types of medications used to treat RA:
Non-steroidal anti-inflammatory drugs (NSAIDs)
Corticosteroids
Disease-modifying anti-rheumatic drugs(DMARDS).
Biologic Response Modifiers (“Bioligics”)

25.  Disease-modifying antirheumatic drugs (DMARDs) or
biologic agents should be started within 3 months of the
diagnosis of rheumatoid arthritis.
Methotrexate ,hydroxycloroquine ,leflunomide ,and
sulphasalsine are commonly used as first line gents
 Nonsteroidal antiinflammatory drugs and/or corticosteroids
should be considered adjunctive therapy early in the course
of treatment and as needed if symptoms are not adequately
controlled with DMARDs.

26. When DMARDs used singly are ineffective or not
adequately effective, combination therapy with
two or more DMARDs or a
DMARD plus biologic agents may be used to
induce a response.
Patients require careful monitoring for toxicity and
therapeutic benefit for the duration of treatment

27. NSAIDs and/or corticosteroids may be used for
symptomatic relief if needed.
They provide relatively rapid improvement in
symptoms compared with DMARDs, which
may take weeks to months before benefit is
seen; however, NSAIDs have no impact on
disease progression and the long-term
complication risk of corticosteroids make
them less desirable

28. Non-steroidal anti-inflammatory drugs
(NSAIDs)

29. Examples General Use Side Effects Monitoring
Considerations
Aspirin, ibuprofen,
naproxen, COX-2
inhibitors, propionic acid,
phenylacetic acid
• anti-
inflammatory:
Used in the
management
inflammatory
conditions
•Antipyretic: used
to control fever
•Analgesic:
Control mild to
moderate pain
•Nausea
•Vomiting
•Diarrhea
•Constipation
•Dizziness
•Drowsiness
•Edema
•Kidney failure
•Liver failure
•Prolonged bleeding
•Ulcers
•Use cautiously in
patients with hx of
bleeding disorders
•Encourage pt to avoid
concurrent use of
alcohol
•NSAIDs may decrease
response to diuretics
or antihypertensive
therapy
(The Arthritis Society, 2011; Day et al., 2010)

30. Corticosteroids

31.  Used in bridging therapy
 Corticosteroids also may be delivered by
injection
 Patients on long-term therapy should be given
calcium and vitamin D or Alendronate to minimize
bone loss.

32. Examples General Use Side Effects monitoring
Considerations
Cortisone, hydrocortisone,
prednisone,
betamethasone,
dexa-methasone
• Used in the
management
inflammatory
conditions
•When NSAIDS
may be
contraindicated
•Promptly
improve
symptoms of RA
•Increased appetite
•Weight gain
•Water/salt retention
•Increased blood
pressure
•Thinning of skin
•Depression
•Mood swings
•Muscle weakness
•Osteoporosis
•Delayed wound
healing
•Onset/worsening of
diabetes
•Take medications as
directed (adrenal
suppression)
•Used with caution in
diabetic patients
•Encourage diet high
in protein, calcium,
potassium and low in
sodium and
carbohydrates
•Discuss body image
•Discuss risk for
infection
(The Arthritis Society, 2011; Day et al., 2010)

33. Disease-modifying anti-rheumatic drugs(DMARDS)

34. Examples General Use Side Effects Monitoring
Considerations
Methotrexate
Hydroxychloroquine
lefulinamide
(the gold standard)
, gold salts,
cyclosporine,
cyclophosphamide
sulfasalazine,
azathioprine
•immunosuppressive
activity
•Reduce inflammation of
rheumatoid arthritis
•Slows down joint
destruction
•Preserves joint function
•Dizziness, drowsiness,
headache
•Pulmonary fibrosis
•Pneumonitis
•Anorexia
•Nausea
•Hepatotoxicity
•Stomatitis
•Infertility
•Alopecia
•Skin ulceration
•Aplastic anemia
•Thrombocytopenia
•Leukopenia
•Nephropathy
•fever
•photosensitivity
•May take several
weeks to months
before they
become effective
•Discuss
teratogenicity,
should be taken off
drug several
months prior to
conception
•Discuss body
image
(The Arthritis Society, 2011; Day et al., 2010)

35. Methtrexate
 DMARD of choice
 CI in chronic liver disease,
immunodeficiency,thrpmpocytopenia,leucopenia,
 preexisting blood disorders , cr <40
 Inhibit cytokine production
 Git side effect , liver toxicity
 Folic acid antagonist
Dose and Administration
Dose ranges from 7.5 to 25 mg
ONLY GIVEN ONCE A WEEK
2.5 mg Tablets or Subcutaneous Injection 25
mg/mL

37. Tetrahydrofolate is an important cofactor in the production of purines
transferring a carbon atom

38. Biologic Response Modifiers (“Bioligics”)

41.  TNF Inhibitors
Adalimumab
Etanercept
Infliximab
 IL-1 Inhibitors
Anakinra
 T-Cell Co-Stimulatory Blockade
Abatacept
 B-Cell Depletion
Rituximab

42. Examples General Use Side Effects Nursing
Considerations
Etanercept,
anakinra,
abatacipt,
adalimumab,
Infliximab (Remicade)
• Used in the
management
inflammatory
conditions
•When NSAIDS
may be
contraindicated
•Promptly
improve
symptoms of RA
•Increased appetite
•Weight gain
•Water/salt retention
•Increased blood
pressure
•Thinning of skin
•Depression
•Mood swings
•Muscle weakness
•Osteoporosis
•Delayed wound
healing
•Onset/worsening of
diabetes
•Take medications as
directed (adrenal
suppression)
•Encourage diet high
in protein, calcium,
potassium and low in
sodium and
carbohydrates
•Discuss body image
•Discuss risk for
infection

43. Therapeutic guideline

45. Triple Therapy
Methotrexate, Sulfasalazine, Hydroxychloroquine
Double Therapy
Methotrexate & Leflunomide
Methotrexate & Sulfasalazine
Methotrexate & Hydroxychloroquine
Methotrexate & infliximab
Sulfasalazine & cyclosporin

46. Dosing

48. EVALUATION OF THERAPEUTIC OUTCOMES
The evaluation of therapeutic outcomes is based primarily on
improvements of clinical signs and symptoms of rheumatoid
arthritis.
Clinical signs of improvement include a reduction in joint swelling,
decreased warmth over actively involvedjoints, and decreased
tenderness to joint palpation. Improvement in rheumatoid arthritis
symptoms includes reduction in perceived joint pain and morning
stiffness, longer time to onset of afternoon fatigue, and
improvement in ability to perform activities of daily living.
Improvement of activities of daily living may be assessed
objectively using a Health Assessment Questionnaire score.
.

49. Joint radiographs may be of some benefit in assessing the
progression of the disease and should show little or no
evidence of disease progression if treatment is effective.
Laboratory monitoring is of little value in monitoring individual
patient response to therapy. Routine monitoring of patients is
essential to the safe use of these drugs.
In addition, patients should be questioned about
symptoms of the adverse effects outlined previously