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Overvie$ of Allergic R%initis &%armacot%era'( of Allergic R%initis Nee) for t%e com*ination of MON#E+LE+O !linical Efficac( of MON#E+LE+O &lace in t%era'(
DEFINITION OF AR
Allergic r%initis is clinicall( )efine) as a s(m'tomatic )isor)er of t%e nose in)uce) *( an gE,me)iate) inflammation after allergen e-'osure.
PROBLEM STATEMENT
Allergic r%initis is one of t%e most common allergic )iseases Affects 15,/0 0 of t%e $orl)1s 'o'ulation n t%e last five )eca)es2 t%e 'revalence of allergic r%initis %as tri'le) from 30 to 140 $orl)$i)e AR is t%e commonest allerg( encountere) in clinical 'ractice in n)ia #%e 'revalence rate is estimate) to *e 50,/00 in n)ia
Priniples & practise of Tropical Allergy & Asthma 2006 Wiqar Shaikh
CAUSES OF AR
CLINICAL FEATURES
Nasal o*struction Nasal )isc%arge &ost,nasal )ri' Sneezing E'ista-is 6ater( e(es Re) e(es tc%ing aroun) e(es
"ea)ac%e or facial 'ain S$elling or )eformit( 7istur*ances of smell Snoring !%ange in voice 8%('er or %('onasalit(9
NASAL ANATOMY
&icture of nose $it%
gE anti*o)(
C$#"o!ac!ic Fac!o%s
His!a"in#
Sneezing tc%ing R%inorr%oea
ROLE OF HISTAMINE IN AR
&la(s a ke( role in t%e 'at%ogenesis or AR Secrete) *( mast cells an) *aso'%ils nfluences t%e activation of several ot%er me)iators of inflammation 8inclu)ing neutro'%ils2 eosino'%ils2 macro'%ages9
Levels increase) in nasal secretions of 'atients of AR !ontri*utes to nasal o*struction 2 sneezing an) r%inorr%oea in AR #%us e-erts a )irect as $ell as in)irect effect
Ref: clinical therapeutics 200 !2":#"#$##2
C$#"o!ac!ic *ac!o%s
L#u)o!%i#n#s
INFLAMMATORY CASCADE
P$os+$o,i+ids P$os+$o,i+as# AA%ac$idonic acid Cyc,oo.y/#nas# P%os!a/,andins 12Li+oo.y/#nas# LTA4 LTB4 C$#"o!a.is o* n#u!%o+$i,s LTC40 LTD40 LTE4
Cysteinyl Leukotrienes
Effects t%e nasal vasculature +ascular 'ermea*ilit( +aso)ilation Mucosal s$elling Con/#s!ion3s!u**in#ss
Ann Pharmacother 2001;35:1274-7
ROLE OF LEU4OTRIENES IN AR
7ilatation of nasal *loo) vessels2 increase vascular 'ermea*ilit( $it% e)ema formation congestion ncrease mucus 'ro)uction Recruitment of inflammator( cells into t%e tissue &romote inflammation *( en%ancing t%e activit( of inflammator( cells 5000 times more 'otent t%an %istamine
CLASSIFICATION OF AR
S#asona, A,,#%/ic R$ini!is &SAR' S(m'toms increase )uring certain times of t%e (ear an) cause) *( out)oor allergens 8e.g; trees2 grasses < $ee)s9 P#%#nnia, A,,#%/ic R$ini!is &PAR' S(m'tom t%at occur (ear,roun)2 causes= )ust, mites an) animal )an)er 8'ets9
ARIA CLASSIFICATION
In!#%"i!!#n! > ? )a(s 'er $eek or > ? $eeks P#%sis!#n! @ ? )a(s 'er $eek an) @ ? $eeks
Mi,d Normal slee' an) No im'airment of )ail( activities2 s'ort2 leisure an) Normal $ork an) sc%ool an) No trou*lesome s(m'toms
Mod#%a!#2S#8#%# One or more terms; A*normal slee' m'airment of )ail( activities2 s'ort2 leisure A*normal $ork an) sc%ool #rou*lesome s(m'toms
APPROACH TO TREATMENT OF AR
Avoi)ance of allergens
Environmental control
&%armacot%era'( mmunot%era'(
gE anti*o)(
C$#"o!ac!ic Fac!o%s
L#u)o!%#in#s
His!a"in#
L#8oc#!i%i7in#
Mon!#,u)as!
Nasal congestion Inflammation
LATE ALLER IC RESPONSE &LAR'
PHARMACOTHERAPY FOR AR
Nasa, P%#+a%a!ion An!i$is!a"in#s Sn##7in/ I!c$in/ R$ino%%$o#a Con/#s!ion Ey# sy"+!o" s ++ 0 ++ 0 ++
+++++
++++ 0 +++++ 0 ++
An!i,#u)o!%i#n#s ++
't is thus reasona(le to consi)er that com(ine) me)iator (locka)e may re)uce the symptoms of allergic rhinitis
ARIA report 2001
ROLE OF MONTELU4AST IN AR
t *elongs to t%at class of )rug $%ic% s'ecificall( *locks leukotrienes2 an un)erl(ing cause of allerg( s(m'toms
:locks L#!? $%ic% is a''ro-imatel( 10 times as 'otent as %istamine :locks L#7? $%ic% $as s%o$n to *e 5000 times as 'otent as %istamine Offers relief from congestion an) stuffiness Gives )a(,time as $ell as nig%t,time s(m'tom relief
ROLE OF LEVOCETRI=INE IN AR
Levocetrizine acts *( *in)ing to t%e "1 rece'tors t%ere*( antagonising t%e effects of %istamine in AR Levocetirizine significantl( attenuate) t%e %istamine in)uce) increases in t%e nasal air$a( resistance $it% almost 500 re)uction over 'lace*o Levocetirizine also significantl( 8&>0.019 re)uce) %istamine in)uce) sneezes Levocetirizine in%i*its eota-in,in)uce) eosino'%il migration t%roug% *ot% )ermal an) lung microvascular en)ot%elial cells suggesting 'otential anti, inflammator( effects
Nig%ttime S(m
8:aseline G 1.59
!om'osite S(m
7a(time E(e
Co":ina!ion $as :##n s$o<n !o :# si/ni*ican!,y su+#%io% !o &lace*o "ono!$#%a+y in %#,i#* o* a,, !$# sy"+!o"s o* SAR Montelukast 10 mg
+ + + + Lorata)ine 10 mg
* *
Montelukast + Lorata)ine
N"#$0 % wee!s
,0.3 DE ,0.F
* P < 0.05 compared with placebo; + P <0.001 compared with placebo; # p < 0.001 compared with montel !ast or loratadine alone
S(m'tom score
DDE J
DDD
E DD
E DDD
mgHcetirizine 10 mg
P<0.01 &s p P%#!%#a!"#n! a,so d#,ays a++#a%anc# o* ** sy"+!o"s? ***P<0.001 &s p + P<0.05 &s 'on # P<0.05 &s (et
LUN
Co":ina!ion $as :##n s$o<n !o :# as #**#c!i8# as :ud#sonid# in !$# %#,i#* o* sy"+!o"s o* AR <i!$ as!$"a ?30
?55 &lace*o :A7 MON+!K
30 ?0 ?0 50
50 /0 50 10
PLACE IN THERAPY
In "od#%a!#2!o2s#8#%# sy"+!o"s o* in!#%"i!!#n! %$ini!is As "ono!$#%a+y in "i,d +#%sis!#n! AR As "ono!$#%a+y in "i,d in!#%"i!!#n! AR P%o+$y,ac!ic !$#%a+y in SAR In as!$"a co2#.is!in/ <i!$ AR
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