Penyakit Paru Obstruktip Kronis (PPOK)

3 penyakit utama tergolong PPOK: Asma bronkhiale Bronkhitis kronis Emfisema pulmonum

Asma bronkial
Gambaran klinik asma bronkial: dikeluarkannya senyawa auta oids yang mempengaruhi saluran paru mulai dari bronkus sampai al!eolus dgn akibat a"l": sesak nafas# dgn gambaran paru sbb: Bronkokonstriksi $nflamasi %edema mukosa bronkus dan &aringan sekitarnya 'ipersekresi kelen&ar mukosa bronkus

B(O)KO*KO)+,($K+$
Otot polos : 1) Kontraksi sebabkan bronchospasmus 2) hypertrophy

Beta agonists Endogenous norepinephrine can stimulate alpha1, alpha-2, beta-1 and beta-2 receptors. ost drugs are created to be either agonists or antagonists that are more selecti!e "or one or t#o receptors. $o#e!er, no substance so "ar has sho#n 1%%& selecti!ity. Beta agonist agents are more selecti!e "or the beta receptors. Beta-1 receptors are abundant in the circulation and skeletal muscle, beta-2 in smooth muscle 'particularly in the respiratory tree). (ommonly used drugs o" this group are ephedrine , salbutamol, salmeterol, and terbutaline.

)nticholinergic e""ects in the lung -agal stimulation of the respiratory tra t.s mus arini * / re eptors auses airway onstri tion" By blo king this parasympatheti stimulation# the anti holinergi agents redu e smooth mus le tone and lead to dilatation of the onstri ted airway" ,here are three prin iple mus arini 012 re eptors: 134postganglioni and 5)+# 1/4postsynapti in heart nodes and myo ardia# and 134postsynapti in smooth mus le# !as ular endothelium and se retory glands" ,he 16 stimulates mole ular me hanisms like the 1/ re eptors but it7s fun tion is un lear" ,he 18 re eptor is like the 13 re eptor and is also found in the 5)+# but it7s role is elusi!e"

)nticholinergics *espite their commonly used name, the +anticholinergic, drugs antagoni-e only the muscarinic receptors. Ipratropium and tiotropium are the t#o anticholinergics 'or parasympatholytics) currently used. Both are only a!ailable "or administration !ia the inhalational route. .pratropium 'the older drug) has no selecti!ity "or 1, 2, or / receptors and lasts "or about 0 hours. $o#e!er, tiotropium is a long-acting anticholinergic #hich can be used once daily. )nticholinergic drugs also e""ect mucus secretion. 1ince systemic anticholinergic drugs can block all muscarinic receptors, tachycardia, increased contractility, blurred !ision, dry mouth, decreased s#eating, constipation, and con"usion are e""ects that can be e2pected in a dose dependent manner.

.n"lammasi pada asma : - increase in number o" in"lammatory cells - edema - dilated blood !essels - e2cessi!e mucus

)ntigen trigger on mast cell 3he membrane o" mast cells has 4c receptors "or speci"ic .gE molecules. 3he .gE molecules get attached to the mast cell #hen it is bound #ith an antigen. 3he .gE-4c receptor binding triggers:

1. the degranulation process 'releasing histamine, proteases, 354 and interleukins) 2. the increased synthesis o" interleukins /. the release o" leukotrienes as #ell as

ast cell stabili-ers )ntihistamines block the e""ects o" histamine already released into the system. )nother means o" blocking the e""ects o" histamine is by pre!enting it6s release "rom in"lammatory cells. Nedocromil and cromoglycate are substances that are thought to #ork by pre!enting degranulation o" mast cells. 3hese agents are only a!ailable by inhalation and are indicated "or the prophyla2is o" mild asthma. 7n"ortunately, poor clinical results #ith these agents limit their utility.

.nhaled steroids 'beclometason and fluticason) are commonly used as "irst line treatment "or the prophyla2is to reduce the chronic in"lammation in asthmatic patients. 1hort pulse o" systemic steroids are sometimes used to treat an acute e2acerbation in an asthmatic patient. 3hese short pulses should ne!er e2ceed t#o #eeks in order to a!oid serious to2icities. ." the respiratory patient re8uires chronic systemic steroids in order to reduce symptoms, the clinician should repeatidily try a slo# taper to the lo#est tolerated

ucolytic agents ucus is largely composed o" glycoproteins. 3hese are large molecules containing se!eral disul"ide bridges. Mucolytic agents are sul"ur compounds 'acetylcysteine) such as 5acetylcysteine that break up the disul"ide bridges making the molecules smaller and the mucus more !iscous. 3hey act mainly #hen applied directly by inhalation or during bronchoscopy. 3heir e""ecti!eness #hen used orally is doubt"ul. (ompletely di""erent "rom sul"ur compounds is *5)se 'not sho#n), #hich clea!es long *5) molecules. .n cystic "ibrosis '(4), in"lammatory cells are abundant in the air#ay lumen and their *5) is released a"ter degradation. 3he long molecules make the mucus !ery sticky. *5)se is o"ten !ery e""ecti!e in (4 making the sputum #atery #ithin a short time. *5)se is not bene"icial to all (4 patients ho#e!er.

1ubmucosal glands are acti!ated by !agal stimulation. 3here is no sympathetic inner!ation

)nticholinergics "or mucus )nticholinergic agents in theory #ill reduce mucus production. 3his could inad!ertently lead to a more sticky secretion in chronic bronchitis and (4 patients. $o#e!er in !i!o studies point out that this anticholinergic acti!ity is clinically rather unimportant. 5e!ertheless some patients do e2perience some dryness o" mouth or throat a"ter inhalation o" ipratropium

9ate in"lammatory mediators any di""erent cells respond to an antigen trigger in an allergic asthma response. :rostaglandins, interleukins, 93B; and 93(; ha!e se!eral actions in in"lammation, and many o" these substances are chemoattractants. 3he increased proli"eration o" these cells leads to the long-term tissue changes seen in chronic asthma

9eukotriene modi"iers 3here are t#o types o" agents that modi"y leukotriene response, inhibitors o" 93 synthesis that block lipo-o2ygenase, and LT receptor antagonists. 3he drugs zafirlukast and montelukast belong to the latter group and are used more clinically. Zileuton is an inhibitor o" leukotriene synthesis .n theory, these 93 modi"ying agents could ha!e a ma<or role in the treatment o" asthma. $o#e!er theory and practice are not identical= many asthmatics appear not to ha!e any bene"it "rom 93 modi"iers, #hich no# are prescribed mainly "or mild asthma or asthma #ith pro"ound e2erciseinduced symptoms.

,erapi thd asma bronkial

Bronkodilatator Obat thd inflamasi dan edema mukosa 1engurangi sekret 0yang berlebihan2 1engatasi hipo9ia ,indakan supportip lainnya: airan #dsb

1a am*ma am obat asma :

+impatomimetika :eri!at 9anthine: theofilin#aminofilin Kortikosteroid" Biskromones: kromolyn# ketotifen" Antikolinergik:ipratropium bromide" +emua obat tersebut diatas utk terapi initial ataupun pen egahan"

,erapi penun&ang
Antibiotika Oksigen# airan $"-" 1ukolitika*mukokinetika: fisioterapi# ambro9ol# asetilsistein0 Efekti!itas kedua obat ini di abang bronkus diragukan2"

Bronkodilatator
+impatomimetika:adrenalin# beta*/ agonist# efedrin" :eri!at 9anthine: teofilin#aminofilin

Adrenaline
:iberikan s" " dosis ke il ;#/ ml larutan 3:3;;; untuk mengatasi serangan akut" Efek samping takikardi# hipertensi dan yg berbahaya bila ter&adi aritmia !entrikuler 0fatal2"

Beta*/ agonist
,ermasuk golongan ini ialah: salbutamol0albuterol2# metaproterenol# ritodrine#terbutaline# fenoterol dll" Golongan ini dapat digunakan per oral# parenteral#dan per inhalasional" Efek samping berupa takikardi# hipertensi dan aritmia

:eri!at 9anthine
,heophylline#aminophylline merupakan antagonist thd reseptor adenosine dan men egah peme ahan A1P dan G1P" :iberikan i"!" atau per*oral" Efek samping:per oral#mual< i"!" terlalu epat dpt depressi &antung":osis besar kon!ulsi"$nde9 terapi ke il"

3heophylline Theophylline is a phosphodiesterase inhibitor, #hich gi!es rise to higher intracellular le!els o" :K) and :K>. 3he increase in :K) and :K> acti!ity is associated #ith smooth muscle rela2ation and decreased in"lammatory responses. 3heophylline is also considered a last-line agent due to it?s pharmacokinetic parameters #hich gi!e it a narro# therapeutic #indo# bet#een e""ectiness and to2icity.

Kortikosteroids
Glukokorti oids: prednisone# de9amethasone# prednisolone Anti*inflamatorik"Prednisolone long*a ting# banyak efek samping dibanding short *a ting: prednisone #de9amethasone" :iberikan sistemik oral atau parenteral" $nhalasi lebih efektip 0efek samping andidiasis2Preparat a"l" Be lomethasone dipropionate"

+odium romogly ate#ketotifen

1ekanisme ker&a tidak diketahui dengan pasti# diduga menghambat pelepasan spasmogens dari sel*sel radang" 'anya untuk pen egahan" Bisa per*inhalational 0 romogly ate2# sering memi u batuk" ,idak mengganggu pertumbuhan#baik untuk anak*anak"

Antikolinergik
$pratropium bromide# merupakan deri!at atropin dengan gugus amine*=uarterner" :iberikan per*inhalasional berupa aerosol<bermanfaat lebih*lebih untuk menekan produksi sekret bronkus" Absorpsi oleh mukosa minimal" :iindikasikan terutama pada bronkitis* kronis dengan ge&ala asmatis"

)5)>E E53 O4 )(73E )13$ )

3he treatment o" acute attacks o" asthma in patients reporting to the hospital re8uires more continuous assessment and repeated ob<ecti!e measurement o" lung "unction. 4or patients #ith mild attacks, inhalation o" beta-receptor agonist is as e""ecti!e as subcutaneous in<ection o" epinephrine. Both o" these treatments are more e""ecti!e than intra!enous administration o" aminophylline. 1e!ere attacks re8uire treatment #ith o2ygen, "re8uent or continuous administration o" aerosoli-ed albuterol, and systemic treatment #ith prednisone or methylprednisolone '%.@ mgAkg e!ery 0 hours). E!en this aggressi!e treatment is not in!ariably e""ecti!e, and patients must be #atched closely "or signs o" deterioration. .ntubation and mechanical !entilation o" asthmatic patients cannot be undertaken lightly but may be li"esa!ing i" respiratory "ailure super!enes.

1ympathomimetics 7sed in )sthma

)lbuterol 'generic, :ro!entil, Bentolin, others) .nhalant: C% gApu"" aerosol= %.%D/, %.@& solution "or nebuli-ation Oral: 2, ; mg tablets= 2 mgA@ m9 syrup Oral sustained-release: ;, D mg tablets )lbuterolA.pratropium '(ombi!ent, *uo5eb) .nhalant: 1%/ g albuterol E 1D g ipratropiumA pu""= / mg albuterol E %.@ mg ipratropiumA/ m9 solution "or nebuli-ation Bitolterol '3ornalate) .nhalant: %.2& solution "or nebuli-ation Ephedrine 'generic) Oral: 2@ mg capsules :arenteral: @% mgAm9 "or in<ection Epinephrine 'generic, )drenalin, others) .nhalant: 1, 1% mgAm9 "or nebuli-ation= %.22 mg epinephrine base aerosol :arenteral: 1:1%,%%% '%.1 mgAm9), 1:1%%% '1 mgAm9)

4ormoterol '4oradil) .nhalant: 12 gApu"" aerosol= 12 gAunit inhalant po#der .soetharine 'generic) .nhalant: 1& solution "or nebuli-ation .soproterenol 'generic, .suprel, others) .nhalant: %.@, 1& "or nebuli-ation= D%, 1/1 gApu"" aerosols :arenteral: %.%2, %.2 mgAm9 "or in<ection 9e!albuterol 'Fenope2) .nhalant: %./1, %.0/, 1.2@ mgA/ m9 solution etaproterenol ')lupent, generic) .nhalant: %.0@ mgApu"" aerosol in G, 1; g containers= %.;, %.0, @& "or nebuli-ation :irbuterol ' a2air) .nhalant: %.2 mgApu"" aerosol in D% and /%% dose containers 1almeterol '1ere!ent) .nhalant aerosol: 2@ g salmeterol baseApu"" in 0% and 12% dose containers .nhalant po#der: @% gAunit 1almeterolA4luticasone ')d!air *iskus) .nhalant: 1%%, 2@%, @%% g "luticasone E @% g salmeterolAunit 3erbutaline 'Brethine, Bricanyl) .nhalant: %.2 mgApu"" aerosol Oral: 2.@, @ mg tablets :arenteral: 1 mgAm9 "or in<ection

)erosol (orticosteroids Beclomethasone 0>-A(# -an eril2 Aerosol: 6;# ?; g@puff in /;; dose ontainers Budesonide 0Pulmi ort2 Aerosol powder: 3A; g@a ti!ation 4lunisolide 0AeroBid2 Aerosol: /8; g@puff in 3;; dose ontainer 4luticasone 0Blo!ent2 Aerosol: 66# 33;# and //; g@puff in 3/; dose ontainer< powder# 8;# 3;;# /8; g@a ti!ation 4luticasoneA1almeterol 0Ad!air :iskus2 $nhalant: 3;;# /8;# 8;; g fluti asone C 8; g salmeterol@unit 3riamcinolone 0ADma ort2 Aerosol: 3;; g@puff in /6; dose ontainer

9eukotriene .nhibitors ontelukast 0+ingulair2 Oral: 3; mg tablets< 6# 8 mg hewable tablets< 6 mg@pa ket granules Ha"irlukast 0A olate2 Oral: 3;# /; mg tablets Hileuton 0Eyflo2 Oral: A;; mg tablets

(romolyn 1odium I 5edocromil 1odium (romolyn sodium Pulmonary aerosol 0generi # $ntal2: ?;; g@puff in /;; dose ontainer< /; mg@/ mF for nebuliDation 0for asthma2 )asal aerosol 0)asal rom2:G 8"/ mg@puff 0for hay fe!er2 Oral 0Gastro rom2: 3;; mg@8 mF on entrate 0for gastrointestinal allergy2 5edocromil sodium 0,ilade2 Pulmonary aerosol: 3"H8 mg@puff in 33/ metered*dose ontainer GO,5 preparation"

ethyl2anthines: 3heophylline I *eri!ati!es )minophylline 0theophylline ethylenediamine# HIJ theophylline2 0generi # others2 Oral: 3;8 mg@8 mF li=uid< 3;;# /;; mg tablets Oral sustained*release: //8 mg tablets (e tal: /8;# 8;; mg suppositories Parenteral: /8; mg@3; mF for in&e tion 3heophylline 0generi # Eli9ophyllin# +lo*Phyllin# Kniphyl# ,heo*:ur# ,heo*/6# others2 Oral: 3;;# 3/8# /;;# /8;# 3;; mg tablets< 3;;# /;; mg apsules< /A"H# 8; mg@8 mF eli9irs# syrups# and solutions Oral sustained*release# ?L3/ hours: 8;# A;# H8# 3;;# 3/8# 33;# /;;# /8;# /A;# 3;; mg apsules Oral sustained*release# ?L/6 hours: 3;;# /;;# 3;;# 68; mg tablets Oral sustained*release# 3/ hours: 3;;# 3/8# 33;# /;;# /8;# /A;# 3;; mg apsules Oral sustained*release# 3/L/6 hours: 3;;# /;;# 3;; tablets Oral sustained*release# /6 hours: 3;;# /;;# 3;; mg tablets and apsules< 6;;# A;; mg tablets Parenteral: /;;# 6;;# ?;; mg@ ontainer# theophylline and 8J de9trose for in&e tion

Other ethyl2anthines *yphylline 0generi # other2 Oral: /;;# 6;; mg tablets< 33"3# 83"3 mg@8 mF eli9ir Parenteral: /8; mg@mF for in&e tion O2triphylline 0generi # 5holedyl2 Oral: e=ui!alent to A6# 3/H# /86# 3?/ mg theophylline tablets< 3/# A6 mg@8 mF syrup :ento2i"ylline 0generi # ,rental2 Oral: 6;; mg tablets and ontrolled*release tablets Note: Pento9ifylline is labeled for use in intermittent laudi ation only"

)ntimuscarinic *rugs 7sed in )sthma .pratropium 0generi # Atro!ent2 Aerosol: 3? g@puff in /;; metered*dose inhaler< ;";/J 08;; g@!ial2 for nebuliDation )asal spray: /3# 6/ g@spray