FARMAKOTERAPI SISTEM ORGAN III

RHEUMATOID ARTHRITIS
EFTA TRIASTUTI
PROGRAM STUDI FARMASI FAKULTAS KEDOKTERAN
UNIVERSITAS BRAWIJAYA
2013
COMPETENCES TARGET

Sign & symptom of rheumatoid arthritis identification

Rheumatoid arthritis management
Patients counseling & education associated with rheumatoid
arthritis and the treatments
CONTENTS
Definition
Epidemiology
Etiology
Causes of autoimmune
Pathophysiology
Signs & symptoms
Normal & RA joint
Diagnosis
DMARDs-Therapy
Inflammation management
Pain management
Therapy algorithm
DEFINITION OF RA
Pain

Limited
Stiffness
function
Chronic
disease
of joint

Limited
Swelling
motion
EPIDEMIOLOGY

More often on women

1-3% women affected

Most often begin at fourth , fifth & sixth decades of life

ETIOLOGY OF RA

Certain cells
Release Attack
RA is an of the
inflammation- healthy
autoimmune immune
causing tissues
disease system do not
chemicals (joints)
work properly
CAUSES OF AUTOIMMUNE
DISEASE
PATOPHYSIOLOGY
PATHOPHYSIOLOGY
ILUSTRATION
SIGNS & SYMPTOMS OF RA
Pain
Lab
Stiffness
finding

Firm
Swelling
lumps

Dry eyes
RA Limited
& mouth function

Loss of Limited
appetite motion

Low Loss of
fever energy
NORMAL & RA JOINT
RA DIAGNOSIS
Physical
Blood test Tools
exam
X-ray late
Warmth joint Anemia (RBC) arthritis show
abnormality joint

Rheumatoid factor
Swelling joint antibody or MRI
blood protein

Antibody to cyclic
citrullinated
Joint pain USG
peptides or anti
CCP

erythrocyte
sedimentation
rate

There is no single test that confirms an RA

diagnosis
RA DIAGNOSIS
Morning stiffness for at least 1 hour and present for at least 6 weeks

Simultaneous swelling of three or more joints for at least 6 weeks

Swelling of wrist, metacarpophalangeal, or proximal interphalangeal joints

for 6 or more weeks

Symmetric joint swelling for 6 or more weeks

Rheumatoid nodules

Serum rheumatoid factor identified by a method that

is positive in less than 5% of normal subjects
Radiographic changes typical of rheumatoid arthritis
on hand or wrist radiographs.
OA & RA DIFFERENCES
HOW IS RA TREATED?
Treatment is to lessen
symptom & poor
function achieve
remission

There is no cure for RA

DMARDs-THERAPY

Px diagnosed Often Relieve

with RA combine with symptoms &
begin with NSAIDs and/or slow
DMARDs corticosteroids progression
 Methotrexate

Biologic agents Leflunomide

COMMON DMARDs

Hydroxychloroq
Cyclosporin
uine

DMARDs
Azathioprine Sulfasalazine

Minocycline Myochrysine

Auranofin
BIOLOGIC AGENTS

FDA approved & have been used since 1998

Lessen inflammation by interfering with biologic

substances that cause or worsen inflammation

Approved by the FDA to treat moderate to severe rheumatoid

arthritis that has not responded to an adequate trial of one or
more of the traditional DMARDs
BIOLOGIC AGENTS MECHANISM
OF ACTION
Monoclonal antibody binds
Infliximab, Rituximab, TNF-a and is used to
Tocilizumab, Etanercept,
Adalimumab
neutralize the action of TNF-
a in inflammatory conditions

IL-1 receptor antagonist

Anakinra
BIOLOGIC AGENTS COMPARISON
BIOLOGIC AGENTS COMPARISON
BIOLOGIC AGENTS COMPARISON
 ANTIFOLATE DRUG
Methotrexate Sulphasalazine

Dihydrofolate reductase prodrug of sulfapiridine

competitive inhibition (sulphonamide) has
Given in a dose of 7.5 antifolate action
mg p.o. per week
initially (max 20 mg)
Adverse reaction
nausea & mouth ulcers
(reduced/ eliminated by
the addition of folic
acid), transient
elevation of hepatic
transaminases
(managed by temporary
discontinuation)
PURINE SYNTHESIS
INHIBITOR

Adverse effects: Precaution:

nausea, diarrhea, Allopurinol, xanthine
Azathioprine is
rash, hypersensitivity oxidase inhibitor,
metabolised to 6-
reactions, marrow potentiates the
mercaptopurine
suppression & action of
hepatotoxicity mercaptopurine
ANTAGONIST T-CELL
FUNCTION

Inhibit production Adverse reactions:

of lymphokines by acute or chronic
T-lymphocytes renal impairment if
Cyclosporine (that mediate plasma
specific concentration
recognition of consistently
antigen molecules) exceeds 250 mg/1
HYDROXYCHLOROQUINE

Less effective than other

Inhibits phagocyte function
DMARDs but it is also less toxic

Adverse effects: retinal

damage, skin discolouration,
Dose: 6.5 mg/kg/d
bleaching of the hair, alopecia,
and gastrointestinal upset
 LEFLUNOMIDE

Selectively inhibits Providing clinical benefit

pyrimidine synthesis & in 4-6 weeks (OOA is Retained in the body for 2
prevents T-cell faster than other years
proliferation DMARDs)

Elimination therapy with Adverse reactions: GI upset,

either cholestyramine or
activated charcoal may be
necessary if a
change to another DMARD
is planned
mouth ulcers, deranged
liver function tests,
hypertension, headache,
leucopenia, weight loss,
erythema, & SJS
GOLD SALTS
Sodium aurothiomalate (im) or auranofin (oral)

Modify cellular and humoral immune responses

T = 22 days; SS concentration after 3 months

Adverse effects: pruritus, dermatitis, glossitis, stomatitis, leukopenia,

thrombocytopenia, marrow failure, hepatic and renal damage, peripheral
neuritis & encephalopathy

Contraindicated in pregnancy
IMMUNOSUPRESSION
MECHANISM
INFLAMMATION MANAGEMENT
INFLAMMATORY MEDIATORS
Interleukins

TNF
Cytokines
Interferons
G-CSF
CSF
Inflammatory
GM-CSF
mediators
Prostaglandins

Thromboxanes
Eicosanoids
Leukotrienes

Lipoxins
 CORTICOSTEROIDS
Relief inflammatory symptoms during the weeks that
it takes DMARDs to act

Methylprednisolone (as sodium succinate) 1 g IV on

3 consecutive day

In extreme severity, high-dose prednisolone (20-40

mg/d)

If DMARDs have failed or have produced intolerable

adverse effects prednisolone 7.5 mg or its
equivalent of other steroid given once daily
CORTICOSTEROIDS
NSAIDs
PAIN MANAGEMENT
NOCICEPTIVE CIRCUIT
Peripheral transduction

Peripheral sensitization
 CENTRAL
SENSITIZATION
SCHEMATIZATION OF NEUROPATHIC PAIN
SITES OF ACTION OF
PAIN MANAGEMENT
 -OPIOID RECEPTOR
AGONISTS MECHANISM
DOSAGE & LABORATORY MONITORING
DOSAGE REGIMENTS FOR NSAIDs
CLINICAL MONITORING OF RA THERAPY
RA ALGORITHM
ESTABLISHED DISEASE

DIAGNOSIS MADE Maintain on a DMARD as

long as joint inflammation
persists
PRE-DIAGNOSIS Introduce DMARD Use sequential DMARDs if
Corticosteroid bridging adverse effects
therapy if necessary Use combination therapy
Analgesics
Continue NSAIDs and of DMARDs if a single
NSAIDs analgesics as needed until agent gives only partial
Intra-articular disease control achieved control
corticosteroids Withdraw NSAIDs or
change to p.r.n. use if
possible
Use Corticosteroid intra-
articular therapy or pulse
therapy for disease flares
GOALS OF THERAPY

Decrease inflammation

Reduce pain

Maintain or restore
joint function

Prevent bone & cartilage

destruction