rheumatoid arthritis

7/21/2019 Rheumatoid Arthritis

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Rheumatoid

arthritisIka Norcahyanti

Bagian Farmasi Klinik & KomunitasFakultas Farmasi UNEJ



Rheumatoid arthritis (RA)

a chronic and usually rogressi!e in"ammatory

disorder o# unkno$n etiology characteri%ed

y olyarticular symmetric 'oint in!ol!ement

and systemic mani#estations

enition**



-istem imun tddr humoral dan cell-mediated

functionKomonen humoral erhu dg ement antiodi

Antiodi ditk di sel lasma

Keanyakan . dg RA memtk A yg diseut dgRHEUMATOID FACTORS (Ig/0 Ig10 IgA)

Ig dt mengakti#kan sist komlemen

-ist komlemen akan memerkuat reson imun& mendorong kemotaksis0 #agositosis0 rilislim#okin o2 sel mononuklear

3athohysiology**



3athohysiology**



4NF (Tumor necrosing factor )0 interleukin56

(I756) & I758 mr sustansi kunci dlm a$aldan kelan'utan RA

9at: !asoakti# (histamin0 kinin0 3/);;++dirilis d tm t'dnya in"amasi;;menyeakan e< aliran darah ke daerahin"amasi0 me< ermea kailer=A-I7 > (KR45F7) edema0 warm0 eritema0nyeri

3athohysiology**



4'd in"amasi kronik d cairan sino!ial

In"amasi ditandai dg roli#erasi memransino!ial ? 3ANNU-

3annus mengin!asi kartilago dan erm tul

erosi tul @ kartilago

destruksi 'oint

3athohysiology**

http://pathophysiology_of_ra.avi/

http://pathophysiology_of_ra.avi/



linical 3resentation**

nonsecic rodromal symtoms that

de!elo insidiously o!er $eeks to months

#atigue0 $eakness0 lo$5grade #e!er0

loss o# aetite0 and 'oint ain

stiness and myalgias may recede

de!eloment o# syno!itis



∗ Joint in!ol!ement tends to e symmetric and aect

the small 'oints o# the hands0 $rists0 and #eetC theelo$s0 shoulders0 his0 knees0 and ankles may alsoe aected

∗ Joint stiness tyically is $orse in the morning0usually e.ceeds D minutes0 and may ersist all day

∗ n e.amination0 'oint s$elling may e !isile or maye aarent only y alation the tissue #eels so#tand songy and may aear erythematous and$arm0 esecially early in the course o# the disease




∗ hronic 'oint de#ormities commonly in!ol!e

sulu.ations o# the $rists0 metacarohalangeal 'oints0 and ro.imal interhalangeal 'oints (s$an5neck de#ormity0 outonniere de#ormity0 ulnarde!iation)

∗ E.tra5articular in!ol!ement rheumatoid

nodules0 !asculitis0 leural eusions0 ulmonaryrosis0 ocular mani#estations0 ericarditis0 cardiacconduction anormalities0 one marro$suression0 and lymhadenoathy




7ocation**



Rheumatoid Factor (RF)

Anti53 (anticyclic cytrullinated etideantiody)

E-R dan R3 <

7eukocytosis

Radiograhs analysis

thers > B

7aoratorium ata**



iagnosis**



lassication**



the ultimate goal o# RA treatment

to induce a comlete remission0 although

this may e diGcult to achie!e

reduce 'oint s$elling0 stiness0 and ainCreser!e range o# motion and 'oint #unctionC

imro!e Huality o# li#eC re!ent systemiccomlicationsC and slo$ destructi!e 'oint changes

utcome**



adeHuate rest0 $eight reduction i# oese0

occuational theray0 hysical theraysurgical rocedures tenosyno!ectomy0tendon reair0 and 'oint relacements

atient education

Non 3harmacology

4heray**



3harmacology

4heray**



∗ 14 inhiits cytokine roduction and urine

iosynthesis0 $hich may eresonsile #or itsantiin"ammatory roerties its onset is

relati!ely raid (as early as : to D $eeks)

∗ 4o.icities are /I (stomatitis0 diarrhea0 nausea0!omiting)0 hematologic (thromocytoenia0

leukoenia)0 ulmonary (rosis0 neumonitis)0and heatic (ele!ated en%ymes0 rare cirrhosis)

concomitant #olic acid may reduce some ad!erseeects $ithout loss o# eGcacy

14 (1AR)+++



∗ Asortion o# 14 is !ariale and a!erages

o# an oral dose∗ 14 is DL5L ound to aluminC it may

dislaced y highly rotein5ound drugs such asN-AIs

∗ 7i!er in'ury tests (asartate aminotrans#erase or

alanine aminotrans#erase) should e monitorederiodically a li!er iosy is recommendedduring theray only in atients $ith ersistentlyele!ated heatic en%ymes

14 (1AR)+++



∗ 14 is teratogenic

∗ 14 is contraindicated in regnant and nursing$omen0 chronic li!er disease0 immunodeciency0leural or eritoneal eusions0 leukoenia0thromocytoenia0 ree.isting lood disorders0and creatinine clearance M m72min

14 (1AR)+++



7e"unomide (Ara!a) inhiits yrimidine synthesis0

$hich reduces lymhocyte roli#eration andmodulation o# in"ammation

Its efcacy #or RA is similar to that o# MTX

A loading dose o# 6 mg2day #or the rst D daysmay result in a theraeutic resonse $ithin the

rst month+ 4he usual maintenance dose o# :mg2day may e lo$ered to 6 mg2day in cases o#/I intolerance0 comlaints o# hair loss0 or otherdose5related to.icity

7e"unomide

(1AR)+++



∗ 4he drug may cause li!er to.icity and is

contraindicated in atients $ith ree.istingli!er disease

∗ 7e"unomide may cause one marro$ to.icityC acomlete lood cell count $ith latelets isrecommended monthly #or 8 months and thene!ery 8 to O $eeks therea#ter

∗ It is teratogenic and should e a!oided duringregnancy

7e"unomide

(1AR)+++



=ydro.ychloroHuine lacks the myelosuressi!e0 heatic0

and renal to.icities seen $ith some other 1ARs0 $hichsimlies monitoring

Its onset may e delayed #or u to 8 $eeks0 ut the drugshould not e considered a theraeutic #ailure until a#ter 8months o# theray $ith no resonse

-hort5term to.icities include /I (nausea0 !omiting0

diarrhea)0 ocular (accommodation de#ects0 enign cornealdeosits0 lurred !ision0 scotomas0 night lindness0reretinoathy)0 dermatologic (rash0 aloecia0 skinigmentation)0 and neurologic (headache0 !ertigo0insomnia) eects

=ydro.ychloroHuine

(1AR)+++



A rodrug0 is clea!ed y acteria in the colon into

sul#ayridine and L5aminosalicylic acid 4he e.act mechanism #or RA is unkno$n

-ul#asala%ine use is o#ten limited y ad!erse eects+Antirheumatic eects should e seen in : months

Ad!erse eects include /I (anore.ia0 nausea0

!omiting0 diarrhea)0 dermatologic (rash0 urticaria)0hematologic (leukoenia0 rare agranulocytosis)0 andheatic (ele!ated en%ymes) eects

/I symtoms may e minimi%ed y starting $ith lo$doses0 di!iding the dose more e!enly throughout the

day0 and taking the drug $ith #ood

-ul#asala%ine

(1AR)+++



4he drugs in this section can e eecti!e and maye o# !alue in certain clinical settings+ =o$e!er0

they are used less #reHuently today ecause o#to.icity0 lack o# long5term enets0 or oth

Aurothioglucose (-olganol) (susension in oil) andgold sodium thiomalate (1yochrysine0 Aurolate)(aHueous solution) are intramuscular (I1) gold

Auranon (Ridaura) is an oral gold rearationthat is more con!enient ut less eecti!e than I1gold+ A%athiorine is a urine analog that iscon!erted to 85mercatourine and is thought to

inter#ere $ith NA and RNA synthesis

ther 1AR+++



3enicillamine is usually reser!ed #or atients

$ho are resistant to other theraies ecauseo# the rare ut otentially serious inductiono# autoimmune diseases (e+g+0 /oodasturePssyndrome0 myasthenia gra!is)

yclosorine reduces roduction o# cytokinesin!ol!ed in 45cell acti!ation and has directeects on B cells0 macrohages0 one0 andcartilage cells

ther 1AR+++



Etanercet (Enrel) is a #usion rotein consisting

o# t$o L5solule 4NF recetors linked to an Fc#ragment o# human Ig/6+ It inds to andinacti!ates 4NF0 re!enting it #rom interacting$ith the cell5sur#ace 4NF recetors and thereyacti!ating cells

1ost clinical trials used etanercet in atients$ho #ailed 1ARs0 and resonses $ere seen in8 to L o# atients

Biology Agent+++



It has een sho$n to slo$ erosi!e disease

rogression to a greater degree than oral14 in atients $ith inadeHuate resonse to14 monotheray

Ad!erse eects include local in'ection5site

reactions0 and there ha!e een case reortso# ancytoenia and neurologicdemyelinating syndromes

Biology Agent+++



Iniximab (Remicade) is a chimeric anti54NF antiody

#used to a human constant5region immunogloulin /6(Ig/6)+ It inds to 4NF and re!ents its interaction $ith 4NF recetors on in"ammatory cells

4o re!ent #ormation o# antiodies to this #oreign rotein014 should e gi!en orally in doses used to treat RA #oras long as the atient continues on in"i.ima

In clinical trials0 the comination o# in"i.ima and 14halted rogression o# 'oint damage and $as suerior to14 monotheray

Autoantiodies and luus5like syndrome ha!e also eenreorted

Biology Agent+++



Adalimuma (=umira) is a human Ig/6

antiody to 4NF that is less antigenic thanin"i.ima

It has resonse rates similar to other 4NFinhiitors

7ocal in'ection site reactions $ere the mostcommon ad!erse e!ent reorted in clinicaltrials

Biology Agent+++



Anakinra (Kineret) is an I756 recetor antagonist (I75

6ra) that inds to I756 recetors on target cells0re!enting the interaction et$een I756 and the cells+I756 normally stimulates release o# chemotactic #actorsand adhesion molecules that romote migration o#in"ammatory leukocytes to tissues

4he drug is aro!ed #or moderately to se!erely acti!eRA in adults $ho ha!e #ailed one or more 1ARs

It can e used alone or in comination $ith any o# theother 1ARs e.cet #or 4NF5locking agents

Biology Agent+++



Aatacet (rencia) is a costimulation modulator

aro!ed #or atients $ith moderate to se!eredisease $ho #ail to achie!e an adeHuateresonse #rom one or more 1ARs

By inding to O2O8 recetors on antigen5resenting cells0 aatacet inhiits interactions

et$een the antigen5resenting cells and 4 cells0re!enting 4 cells #rom acti!ating to romote thein"ammatory rocess

Biology Agent+++



Ritu.ima (1athera) is a monoclonal chimeric antiodyconsisting o# mostly human rotein $ith the antigen5

inding region deri!ed #rom a mouse antiody to :

rotein #ound on the cell sur#ace o# mature B lymhocytes+Binding o# ritu.ima to B cells results in nearly comletedeletion o# eriheral B cells0 $ith a gradual reco!eryo!er se!eral months

Ritu.ima is use#ul in atients #ailing 14 or 4NF inhiitors

1ethylrednisolone 6 mg should e gi!en D minutesrior to ritu.ima to reduce the incidence and se!erity o#in#usion reactions

Acetaminohen and antihistamines may also enetatients $ho ha!e a history o# reactions

Biology Agent+++



N-AIs act rimarily y inhiiting

rostaglandin synthesis0 $hich is only a smallortion o# the in"ammatory cascade

4hey ossess oth analgesic andantiin"ammatory roerties and reduce

stiness ut do not slo$ disease rogressionor re!ent ony erosions or 'oint de#ormity

4hey should seldom e used as monotheray#or RA

N-AI+++



orticosteroids ha!e antiin"ammatory and

immunosuressi!e roerties 4hey inter#ere $ith antigen resentation to 4lymhocytes0 inhiit rostaglandin and leukotrienesynthesis0 and inhiit neutrohil and monocytesuero.ide radical generation

ral corticosteroids (e+g+0 rednisone0methylrednisolone) to control ain and

syno!itis $hile 1ARs are taking eect(Qridging theray)

orticosteroid+++



=igh5dose oral or intra!enous ursts may e

used #or se!eral days to suress disease "ares a#ter symtoms are controlled0 the drugshould e taered to the lo$est eecti!e dose

Ad!erse eects o# systemic glucocorticoids limittheir long5term use

osage taering and e!entual discontinuationshould e considered at some oint in atientsrecei!ing chronic theray

orticosteroid+++



linical signs o# imro!ement include reduction in 'oints$elling0 decreased $armth o!er acti!ely in!ol!ed 'oints0

and decreased tenderness to 'oint alation-ymtom imro!ement includes reduction in 'oint ainand morning stiness0 longer time to onset o# a#ternoon

#atigue0 and imro!ement in aility to er#orm dailyacti!ities

3eriodic 'oint radiograhs may e use#ul in assessingdisease rogression

7aoratory monitoring is o# little !alue in monitoringresonse to theray ut is essential #or detecting andre!enting ad!erse drug eects

E!aluation+++



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rheumatoid arthritis

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