Artritis Rheumatoid. Pharmacology. Pharmacotherapy. Pharmacy

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Autoimmune systemic diseases


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A relatively large group of diseases

Eg.: Rheumatoid arthritis

Systemic lupus erythematosus

Systemic sclerosis

Vasculitis

Mixed connective tissue disease

Antiphospholipid syndrome

Juvenile idiopathic arthritis

and other….


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Rheumatic Arthritis


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chronic, systemic, inflammatory disease

yet unknown etiology

affects approximately 1% of the population

women 3 times more frequently affected than men

Clinically, joint inflammation that manifests as:

joint pain,

stiffness

impaired function

swelling of soft tissues around joints – symetr.

Prolonged inflammation leads to joint deformities

and their destruction or ankylosis.

Rheumatic arthritis


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Immunologic findings

rheumatoid factors (RF) are about 80% of

cases of RA.

Positive antinuclear antibodies (ANA) are in 30 to

50% of cases.

Elevated circulating immune complexes are, the

higher are the immunoglobulins, especially IgG.

Acute phase reactants - higher sedimentation rate

and CRP.

Blood count - normally occurs anemia which

correlates with disease activity.

Typical laboratory findings observed in RA


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Analysis of synovial fluid is an important examination.

Synovial fluid is usually inflammatory - it has a yellow

and turbid, whitish or green tint. It has greatly reduced

viscosity.

Imaging methods - even though some are beginning

to promote new techniques (NMR, arthrosonografie), in

routine practice is still the gold standard of classical X-

ray.


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Systemic lupus erythematosus


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Treatment


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Treatment

NSAIDs

Steroids

DMARDs

Gold

Antimalarics

Imunosupressants

Biological m.

Treatment goals:

o Relieve symptoms

o Preserve joints‘ function

o Prevent further disease progression

o Improve QoL

o Deal with extraarticular manifestation

o MAINTAIN MOBILITY!!!


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Usually first-line drugs

but also are often used in combination with other

(DMARDs or corticosteroids).

Reduces pain and stiffness and improve patients

quality of life.

do not suppress the acute phase reactants and braking

X-ray progression.

Relatively high toxicity: NSAID-induced gastropathy

and its complications (ulcers, bleeding, perforation).

NSAIDs


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Gastrotoxicity of NSAIDs:

o increased with concomitant use of corticosteroids.

o preferential COX-2 + particularly specific inhibitors of

COX-2 – decreased risk.

o Consider: concomitant administration of misoprostol.

The basic division of the NSA

Non-selective COX inhibitors - aspirin, ibuprofen,

naproxen, ketoprofen, diclofenac, indomethacin,

piroxicam, etc.

Preferential COX-2 inhibitor - nimesulide, meloxicam,

nabumetone

Selective COX-2 inhibitors - coxibs (rofecoxib,

celecoxib)

COX inhibitors


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GIT

o Nausea, indigestion, ulcer

Renal

oReversible acute renal failure

Respiratory

oExacerbation of AB

CNS

oHeadache, drowsiness, confusion

Skin

o rashes

Side effects of NSAIDs


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Rather heterogeneous group

Different levels of selectivity COX2/COX1 (celecoxib <

etoricoxib )

endoscopic studies after 6 months showed greater

gastrointestinal toxicity than with placebo (rofecoxib,

celecoxib)

Renal toxicity is not significantly different from

traditional NSAIDs

Cardiotoxicity was demonstrated in a study of rofecoxib

in patients receiving more than 18 months; similarly

celecoxib

EMEA - 'Efect class "families coxibs

Coxibs


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+ Modification of the inflammatory process, slowing

radiological progression of joint damage.

- Takes a long time before its effects (weeks to months),

quite a lot of side effects.

Antimalarials: chloroquine, hydroxychloroquine

sulfasalazine

penicillamine

Gold salts: aurothiomalate, auranofin

Cytotoxic agents: methotrexate,

azathioprine,

cyclophosphamide

Immunosuppressant:cyclosporin

Disease-modifying drugs (DMARDs)


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Strategy for to use of DMARDs has significantly changed.

For long time was valid the pyramid model, ie. sequential

use of DMARDs from those little for the most effective.

DMARDs were used only after the failure of the NSA.

Nowadays DMARDs are used early and continuously.

Overall, procedures are more aggressive, especially in early

disease. Even higher doses of DMARDs are used.

Refractory forms: combination therapy of more DMARDs.

Decreased use of penicillamine and Au salts (due to

toxicity).

Strategy for the use of DMARDs


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Antimalarials (for low active disease)

Sulfasalazine (for medium and less active)

Methotrexate (for medium and highly active form)

the most widely used DMARD at all

Cyclophosphamide, azathioprine and cyclosporine A:

is used primarily in situations exartricular disability

(eg, vasculitis, pulmonary fibrosis)

Or then the disease is unmanageable.

Toxicity and their oncogenic potential during long-

term use.

Strategy for the use of DMARDs


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4-6 weeks before the effect

1x weekly – s.c., i.m.

no alcohol, teratogenic

Monitor – kidney, liver, blood count

+ Folid acid

1x weekly

A day after MTX

x nausea and stomatitis

To report:

Dyspnoea, cough (pulm. Tox.)

Bruising, bleeding (trombocytopaenia)

Sore throat, fever (neutropaenia)

Methotrexate (MTX)


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Leflunomide (Arava ®)

an inhibitor of pyrimidine synthesis.

as effective as MTX and SAS and has a slowing effect

on the X-ray progression.

Used as a second drug options for patients who are

intolerant to or have the effect of MTX and SAS.

Used as monotherapy or in combination with MTX.

Biological treatment

It works against TNF, a key cytokine participating in

chronic inflammation

Infliximab (Remicade ®)

Etanercept (Enbrel ®)

Other DMARDs


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Are currently used in clinical practice, 4 groups of drugs

with different target destination

TNF

Infliximab (Remicade ®)

Etanercept (Enbrel ®)

Adalimumab (Humira ®)

IL-1 - anakinra (Kineret ®)

molecule CD20 - rituximab (Mabthera ®)

molecule CD80/86 - abatacept (Orencia ®)

In the phase of clinical testing there are molecules that

specifically inhibit other targets in parts pathologic immune

system, such as IL-6 (tocilizumab)

Biological drugs


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Application of CS can be divided into systemic and local

(intra-articular).

Systematically used the most so-called "small doses" CS,

which is called dose to 10 mg of prednisone or equivalent

daily.

Symptomatic effect these doses is not great but they

suppress the X-ray progression of damage.

During the high activity or extraarticular complications:

Temporar use of higher doses ranging from 20 to 80

mg of prednisone daily

An alternative is to use pulse therapy (eg 3 times

every day of 1000 g prednisolone iv)

Corticosteroids


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Local intra-articular treatment of CS is recommended

especially when high or persistent oligoarticular activity.

Synoviorthesis – „bloodless synovectomies“

- performed to rapidly suppress the synovitis when ia

corticosteroids were not effective

Other options

The other possible methods practically use only

Yttrium 90 application (pure β emitter)

Corticosteroids


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symptomatic slow acting drugs of osteoarthrosis

anti-inflammatory and analgesic activity comparable with

NSAIDs.

Effects take place gradually within 4-6 weeks and persists

for several weeks after withdrawal.

They dont have the typical side effects of NSAIDs and can

reduce their consumption.

Glucosamine sulphate (Dona ®)

Chondroitin sulfate (Condrosulf ®)

Diacerein (Artrodar ®)

Hyaluronic acid (I.A.) (Hyalgan ®)

SYSADOA


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anti-inflammatory effect is NOT by inhibiting

cyclooxygenase - no side effects typical for NSAIDs

suppress the formation of free radicals

decrease the activity of enzymes degrading intercellular

matrix of cartilage

stimulate chondrocytes to produce proteoglycans

collagen, hyaluronate and other extracellular matrix

components

hamper or slow down the further destruction and loss of

articular cartilage.

SYSADOA


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Eating habits

depending on the drug therapy

(corticosteroids, NSAIDs)

weight reduction

reduction of irritating foods

Physical activity

Psychotherapeutic approaches

Other recommendation


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Devices


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Thank you for your attention

Artritis Rheumatoid. Pharmacology. Pharmacotherapy. Pharmacy

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