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1 Korean J Fam Pract. 2012;2: 쉽게처방하는감기약물다시보기 : Antitussives, Expectorants, and Mucolytics 분류와기전을중심으로 Symposium 남가은, 김도훈 * 고려대학교의과대학교실 The Use of Antitussives, Expectorants, and Mucolytics in Clinical Practice Ga Eun Nam, Do Hoon Kim* Department of Family Medicine, Korea University College of Medicine, Seoul, Korea Acute upper airway infection includes acute nasopharyngitis (common cold), acute sinusitis, acute pharyngitis, and acute epiglottitis. It can also be referred to as acute nasopharyngitis in the narrower sense. Cough and sputum are the common symptoms of these diseases. Specific treatments are needed for these symptoms according to their underlying causes. However, empirical therapies using drugs such as antitussives, expectorants, and mucolytics are applied to symptomatic relief in certain situations. The effects of these drugs are not clearly demonstrated and do not last long. The aim of this review is to examine the list, mechanism, clinical characteristics, and directions for the use of these drugs currently available for the common cold. Keywords: Common Cold; Antitussive Agents; Expectorants; Mucolytics 서론 급성상기도감염은급성비인후염 ( 감기 ), 급성부비동염, 급성편도염, 급성후두개염을모두포함하는용어로좁은의미로는급성비인후염을말한다. 전세계적으로급성상기도감염은병원을찾는가장흔한원인으로사회경제적부담이매우큰질환이며, 공통된주된증상으로기침과객담을들수있다. 기침은기도로이물질이들어가는것을예방하는정상적인방어기전이나지나치게되면환자나의사에게모두매우 불편한증세이다. 객담역시호흡기에서정상적으로분비되 Received: November 10, 2012, Accepted: December 5, 2012 *Corresponding Author: Do Hoon Kim Tel: , Fax: kmcfm@hanmail.net Korean Journal of Family Practice Copyright 2012 by The Korean Academy of Family Medicine 면기도점막을보호하는기능이있으나과도할경우환자에게괴로움을준다. 이러한증세는원인질환에따른특이치료가필요하나, 여의치않을경우비특이적인진해거담제를사용하게된다. 진해거담제는크게진해제 (antitussives), 거담제 (expectorants), 점액용해제 (mucolytics) 로분류된다. 진해제는기침의원인에관계없이기침을가라앉히는약을말한다. 거담제란환자에게고통을주는끈끈한점액을녹여서묽게만들어기도밖으로배출시키는약을말하는반면, 점액용해제는폐에있는점액을분해하여호흡기분비물을묽게만드는데까지만역할을하는데, 이러한거담제와점액용해제의차이를인지하는것이중요하다. 본강좌에서는감기에흔히처방되는진해거담제의종류와작용기전및임상적특징, 사용시주의사항을중심으로살펴보고자한다. 기침반사 기침반사 (cough reflex) 수용체는인후두등의상기도와기 Vol. 2, No. 4 Dec

2 Ga Eun Nam, et al: The Use of Antitussives, Expectorants, and Mucolytics 관의후벽, 기관분기부 (carina), 주기관지등의하기도에주로분포되어있다. 작은기도로가면서희박하게분포하며주로분지부에많으나폐실질내에는거의없다. 1) 기침반사수용체는기도외에도흉막, 고막, 부비동, 횡격막, 심낭, 위, 식도등에분포한다. 기계적기침수용체는접촉이나변형에반응하고, 화학적기침수용체는자극성기체나연기에예민하다. 기침반사수용체가자극을인식하면미주신경을통해뇌간으로자극을전달하고, 호흡근육에분포하는척수신경세포들을흥분시켜기침을유발한다. 1) 진해제 진해제 (Antitussives) 는작용기전에따라중추작용약물과말초작용약물로나뉜다 (Table 1). 중추에작용하는약물은마약류 (narcotic opioids), 마약유도체 (non-narcotic opioids), 비마약류 (nonopioid) 로나눌수있다. 대표적인마약류약제는 codein, hydrocodone, morphine 등으로결과가일정하지않으나제한적인기침억제효과가증명이되었고, 2-4) 적정용량에서도졸음, 변비, 소화장애, 남용이나의존의위험이있다. 마약유도체진해제인 dextromethorphan은기침약및일반감기약에흔히포함되는약제이나이약제의진해효과역시일정하지않다. 2-4) 기침반사의과감작 (hypersensitivity) 에있어중요한기전의하나는시냅스후세포에위치한 N-methyl-Daspartate (NMDA) 수용체의상향조절 (up regulation) 이다. 5) Dextromethorphan은약한 NMDA 수용체길항제로작용해진 해효과를나타내는것으로생각된다. 마약류약제는남용의우려가있어주의해야하며, 가급적이면마약유도체나비마약류약제를사용하는것이좋겠다. 흔히사용되고있는진해제에는단일성분약제와항히스타민제를포함한여러약제의복합제제가있다. 시럽형태로된약제중코푸시럽에스 (cough syrup S ) 와코푸시럽 (cough syrup ) 및코데날시럽 (codenal syrup ) 은약국에서판매되는종합감기약과함께대표적인복합제제이다 (Table 2). 코푸시럽에스에는 dextromethorphan, 에페드린성분과항히스타민제인페니라민이포함되어있어졸음이올수있다. 1,4) 코푸시럽에는 dextromethorphan 대신에소량의코데인이포함되어있어역시졸음을유발할수있다. 코데날시럽은항히스타민제와소량의코데인, guaifenesin을주성분으로한다. 1) 일반적으로객담을동반하는기침에 guaifenesin를포함한약물을사용하고, 객담을동반하지않는기침에는 dextromethorphan, codeine을사용한다. 1) 레보투스 (levotuss ) 는 levodropropizine 성분의진해제로기침의경로중 C-fiber를억제하여기침을억제한다. 또한건조아이비잎추출물 (ivy-leaf dried extract) 로 hederocoside C가주성분인푸로스판 (prospan ) 은진해및거담작용이있으며, 1) 항염증효과및기도평활근이완효과가보고되었다. 여러연구에서오래된 1세대항히스타민제가진해효과를갖고있음이증명되었다. 6) 새로운항히스타민제의경우진해효과가없으므로, 7) 1세대약제의중추신경계침투효과및항콜린성작용이그기전일것으로추측된다. 8) 항콜린제 Table 1. Currently available drugs with proven or potential antitussive effect. Antirussives Drugs Proven antitussives Centrally acting Narcotic opioids: morphine, codein, hydrocodone Non-narcotic opioids: dextromethophan Non-opioid: benproperine, zipeprol, older generation antihistamines Peripherally acting Benzonatate, levodropropizine, guaifenesin, moguisteine Potential antitussives (drugs approved for other indications; not approved as antitussives) Centrally acting: amitriptyline, baclofen, gabapentin, pregabalin Peripherally acting: tiotropium, leukotriene receptor antagonist Non-pharmaceutical agents: theobromine From Kim SH. Korean J Med 2010;78: ) 290 Vol. 2, No. 4 Dec 2012 Korean J Fam Pract

3 남가은외 : 쉽게처방하는감기약물다시보기 인 ipratropium bromide 흡입제도감기및만성기관지염에의한기침환자에서효과가있는것으로보고되었는데유사한기전으로효과를나타낼것으로추정된다. 4) 또한일시적으로 ephedrine이나 phenylnephrine이들어있는분무형비충혈제거제가사용될수도있지만이러한제제는장기간사용시약제 에의한비염이생길수있어주의가필요하다. 9) Benproperine( 코프렐 ) 이나 zipeprol( 레스피렌 ) 도중추에작용하는진해제로흔히사용되고있으나인간을대상으로하는이중맹검연구가존재하지않는다. Benproperine을복용할경우졸음, 어지러움, 피로, 식욕부진, 복통등이흔히나 Table 2. Commonly used syrup form antitussives in South Korea. Brand name Component Usual dose (adult) Effects Cough syrup s Cough syrup Codenal syrup In 100 ml: dextromethorphan 75 mg, methylephedrine HCl mg, chlorpheniramine maleate 15 mg, ammonium Cl 1 mg In 100 ml: dihydrocodein 50 mg, methylephedrine HCl mg, chlorpheniramine maleate 15 mg, ammonium Cl 1 mg In 100 ml: dihydrocodeine 50 mg, guaifenesin 375 mg, methylephedrine HCl mg, chlorpheniramine maleate 15 mg 20 ml tid or qid Antitussive, expectorant, antihistaminic effect 20 ml tid or qid Antitussive, expectorant, antihistaminic effect 20 ml tid or qid Antitussive, expectorant, analgesic, antihistaminic effect Levotuss Levodropropizine 6 mg/ml 10 ml tid Antitussive Prospan Dried ivy leaf extract: hederocoside C 0.35 mg/ml ml tid Inhibitory effects on bronchospasm, expectorant, anti-inflammatory effect From Kim SK and Chang J. Tuberc Respir Dis 2006;60: ) Table 3. Summary of studies on peripherally acting and potential antitussives. Drug Author/reference no./year No. Subjects Study results Peripherally acting antitussives Levodropropizine vs. placebo Allegra and Bossi 12) (1988) 194 Acute and chronic bronchitis Cough severity/frequency 72% (P<0.05) Moguisteine vs. placebo Aversa et al. 14) (1993) 97 COPD, pulmonary neoplasm, pulmonary fibrosis, unknown, other Cough frequency 42% (P<0.03) Moguisteine vs. placebo Adams et al. 15) (1993) 108 URI Significant difference in nighttime cough severity (P<0.05) Guaifenesin, benzotate vs. placebo Dicpinigaitis et al. 16) (2009) 30 URI Cough reflex sensitivity (P<0.05) Guaifenesin vs. placebo Dicpinigaitis and Gayle 17) (2003) 14 URI Cough reflex sensitivity (P<0.05) Potential antitussives Amitriptyline vs. codeine/guaifenesin Jeyakumar et al. 20) (1988) 28 Postviral vagal neuropathy Improved cough-specific qualityof-life (P<0.05) Tiotropium vs. placebo Dicpinigaitis et al. 18) (2008) 21 URI Inhibition of cough reflex sensitivity (P<0.05) Baclofen vs. placebo Dicpinigaitis and Dobkin 23) (1997) 20 Healthy adults Elevation of capsaicin cough threshold (P<0.05) COPD: chronic obstructive pulmonary disease, URI: upper respiratory tract infection. Vol. 2, No. 4 Dec

4 Ga Eun Nam, et al: The Use of Antitussives, Expectorants, and Mucolytics 타나고 zipeprol은과량복용시환각작용이있어서특히젊은층에서오남용의우려가있다. 국내에서 년사이총 61명이 ziperol 남용으로사망했다는보고도있었다. 10) Dextromethorphan 역시 ziperol 과유사한환각효과로청소년사이에서남용이문제된바있으며, 11) 현재단일성분제제인러미라정은생산허가가취소되었다. 말초에작용하는진해제중흔히사용되는약제인 levodropropizine( 레보투스정 or 시럽 ) 은급성및만성기관지염환자에서위약보다효과가우월하였고, 12) 폐암으로인한기침에도코데인과비슷한효과를보였다 (Table 3). 13) Moguisteine 14,15) 역시말초신경계에작용하는것으로생각되며, 급성상기도감염및만성폐쇄성폐질환, 폐암등의환자에서기침을줄여주는것으로보고되었으나국내에서는시판되지않고있다. Benzonatate 는 procaine과구조적으로유사하고 stretch 수용체를억제하여진해효과를보이는데, 국내에서지콜캅셀이라는상품으로시판되고있다. 미국에서도사용이승인되었으나최근급성상기도감염환자를대상으로한연구에서위약에비해의미있는기침감소를보여주지는못했고, guaifenesin과병용투여시효과를증가시키는것으로밝혀졌다. 5,16) 최근미국에서 benzonatate 의남용으로인한심각한부정맥및경련발생의위험이보고되어사용시주의가필요하다. Guaifenesin는객담양을증가시키고점성을줄여객담배출을용이하게하는작용이있어거담제로잘알려져있으나위약대조연구를통해급성상기도감염에서의진해효과도입증되었다. 16,17) Guaifenesin의진해효과는말초와중추에함께작용할것으로생각된다. 복합제제인종합감기약형태로약국에서판매되고있으며, 페나투신캅셀이라는상품명의단일성분제제로도시판되고있다. 진해제로허가받지는않았지만기침억제효과가있음이보고된약제들도있다. 삼환계항우울제인 amitriptyline이나 γ-aminobutyric acid 수용체작용물질인 baclofen, 항콜린제인 tiotropium 등의약제는기침억제효과가있음이보고되었다 (Table 3). 2,18-23) Gabapentin과 pregabalin은시냅스전세포의전위작동칼슘통로 (voltage gated calcium channel) α2δ 아단위를차단함으로써시냅스안으로 glutamate의방출을방해하는항경련제로여러연구에서기침을억제하는효과를보였다. 특발성만성기침 (idiopathic chronic cough) 24) 이나미주신경감각병증 (vagal sensory neuropathy) 25) 환자에서 gabapentin 치료로기침의호전을보였다는연구도있고, 만성기침을호소하는인후감각신경병증 (laryngeal sensory neuropathy) 26) 환자에서 pregabalin 이도움이되었다는보고도있다. Theobromine (Anycough ) 는코코아에서유래된메틸잔틴유사성분으로, 말초에작용하 는천연약물이면서비마약성진해제라는장점이있다. 동물을이용한기침유발검사에서효과를증명하였으나 27) 임상시험에서아직까지효과가충분히검증되지않았다. 펠라고니움시도이데스 (Pelargonium sidoides) 추출물 (Umckamin syrup ) 역시급성상기도감염환자에서진해효과가있음이보고되었다. 28) 거담제및점액용해제 (Expectorants and Mucolytics) 객담의주성분은점액으로수분이 95% 이고, 나머지 5% 는당단백질, 지질및무기질등으로구성된다. 당단백질의구조가선형중합체이중구조로겔형태이기때문에끈적이는양상을보인다. 1) 널리사용되고있는거담제와점액용해제가 Table 4에제시되었다. 흔히거담제라고부르는약제들은대부분이점액용해제 (mucolytics) 로급만성호흡기질환에서증상완화를위해사용되지만위약대조시험에서효과가일정치않아가능한짧은기간사용이권유된다. 4) 만성기관지염환자에서도기침을억제하기위하여이들약제를지속적으로투여하는것은좋지않으며항콜린제를투여하는것보다이득이있을것으로생각되지않는다. Guaifenesin, bromhexine (Mucosol, Bisolvon 등 ) 등의약제는위장관자극으로위와기도분비물을증가시킨다. Guaifenesin은거담제로분류되는대표적인약제로만성기관지염에서객담의양과질을호전시켰다고보고되었으나객관적인자료는부족하다. 하지만오랜기간부작용이별로없었고저렴한가격등으로인해많은감기약에포함되어판매되고있다. Bromhexine은만성기관지염, 기관지확장증환자에서객담양을줄일수있었지만기침을호전시키지는못했다. 4,29) Table 4. Currently available mucolytics and expectorants. Mucolytics Expectorants N-acetylcysteine Ambroxol Bromhexine Guaifenesin Ivy-leaf dried extract Erdosteine Myrtol 292 Vol. 2, No. 4 Dec 2012 Korean J Fam Pract

5 남가은외 : 쉽게처방하는감기약물다시보기 항콜린제인 ipratropium bromide 역시거담효과를보인다. Acetylcysteine (Muteran, Mucosten 등 ) 은점액을용해시켜객담배출을쉽게한다. 만성기관지염에서사용되는 acetylcysteine 분무흡입제는분비물을묽게하지만객담생성을줄이지는못하며기관지수축효과가있다. 항산화작용이있다고알려진 erdosteine (Erdos 등 ) 은경구투여하면간에서대사되어 cysteine 제제와유사한효과를보이며, 만성폐쇄성폐질환자에서악화및입원뿐아니라질병관리비용도줄인다고보고된바있다. 30) 또한 erdosteine은 amoxicillin과병용시 amoxicillin의조직내농도를높여효과를증진시키는작용도있다. 31) 국내에서는건조아이비잎추출물 (Prospan ) 도흔히사용되고있는데 1) hederocoside C가주성분으로진해및거담효과가있다고알려져있으나, 독일등유럽국가에서의몇몇연구를제외하고아직까지무작위위약대조군연구결과가부족하다. 그외에점액조절제로는항콜린제, 스테로이드, 인도메타신, 마크로라이드항생제등이있으며점액활성제로기관지확장제, 표면활성제등이있다. 31) 그리고수분섭취가적절하지못해탈수되면객담배출에방해가되므로목이마르지않을정도의수분섭취가필요하며과다하게물을많이마시는것이도움이되지는않는다. 1) 그밖의대증적치료를위한약물 감기에대한대증적치료로열이나경한오한, 근육통, 두통등의증상을경감시키기위해 acetaminophen을처방할수있다. 32) 상기도감염의증상이면역반응때문에생기고비스테로이드계항염증제 (NSAID) 의투여로염증반응을줄일수있음이알려지면서감기에 NSAID를투여하는것이효과적이라는견해가있다. 실험적으로유발시킨상기도감염이나자연적으로생긴감기에 NSAID를투여한연구들에서감기로인한증상의의미있는호전을보였다고보고되었다. 또한감기증상의완화에 pseudoephedrine 단독투여에비해 ibuprofen을동시에투여하였을때더효과적이었다는연구결과도있다. 33) 그러나 NSAID는두통이나근육통등의통증에비해다른증상에는이득이적고유병기간을줄이지는못하며, 34) 위장관출혈이나고령등의상황에서는사용에주의가필요하다. 한편, 흔히처방되고있는약제중 lysozyme, streptodornase 등의효소형소염제는도움이된다는근거를찾기는어렵다. 35) 1세대항히스타민제는단독으로사용하거나비충혈완화제와함께사용했을때일부감기증상의완화효과를보인다. 졸리는부작용이있어운전이나위험한근무를하는사람에게는주의를요하며, 감기로수면장애를겪는경우도움이될수도있 다. 비강내분무형제제는졸음을피할수있다. 2세대항히스타민제는항콜린작용이없어감기증상에는효과가없다. 비충혈이동반된경우 pseudoephedrine이많이처방되는데혈압을상승시킬수있다. 기관지확장제중 beta2-agonists는기도평활근에직접작용하거나간접적으로는기관지수축화학매체의분비와기관지수축신경전달물질의분비를억제시켜기도확장을일으키며, 기관지점막부종의발생을억제하고점액분비를증가시킴으로써기도상피의 mucociliary clearance를증가시키고기침을감소시키는효과를나타낸다. 1) 감기약물사용시주의사항 일반적인주의사항은다음과같다. 시럽형태의진해제는당분이포함되어당뇨병환자에게투여시에주의가필요하다. 약제를씹어서복용하게되면구강마취효과를유발할수있어씹지않고삼키는것이좋다. 임신이나수유중투여에있어안전성이확립되지는않아사용시주의가필요하며고령자에게는감량투여를고려해야한다. Levodropropizine은 24개월이하유소아나, 중증신부전이있는경우의식장애시에사용해서는안된다. Erdosteine은간경변환자나시스타치오닌합성효소 (cystathionine synthase) 결핍환자에서금기이다. 31) 과당불내성인경우건조아이비잎추출물을사용해서는안되며, N-acetylcysteine과 acetylcysteine 은소화성궤양이있는환자에서금기이다. 31) Ambroxol은중증신장애가있는경우, myrtol은신결석이나담석증환자에게는사용을피하는것이좋다. 결론 급성상기도감염의증상을완화시키기위해비특이적인치료를하게되는데흔히진해제와거담제, 점액용해제를사용하게된다. 일반적으로이들약제는환자의증세호전에도움을줄수있으나효과가분명하지않고장기간사용시효과가입증되지않아임상적으로적응이되는경우에한하여최소한사용하는것이좋겠다. 요약 급성상기도감염은급성비인후염 ( 감기 ), 급성부비동염, 급성편도염, 급성후두개염을포함하며좁은의미로는급성비인후염을말한다. 증상으로는기침과가래가흔한데원인에 Vol. 2, No. 4 Dec

6 Ga Eun Nam, et al: The Use of Antitussives, Expectorants, and Mucolytics 따른특이적인치료가필요하지만증상완화를위해경험적으로진해거담제를사용하는경우가있다. 진해거담제의효과는분명하지않고장기간사용시효과가입증되지는않았다. 본종설에서는감기에흔히처방되는진해거담제의종류와작용기전및임상적특징, 사용시주의사항에대해살펴보고자한다. 중심단어 : 감기 ; 진해제 ; 거담제 ; 점액용해제 REFERENCES 1. Kim SK, Chang J. Respiratory symptoms relievers: antitussives, mucolytics, antihistamines. Tuberc Respir Dis 2006;60: Dicpinigaitis PV. Currently available antitussives. Pulm Pharmacol Ther 2009;22: Bolser DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):238S-249S. 4. Kim SH. Antitussives, mucolytic agents and expectorants in clinical practice. Korean J Med 2010;78: Young EC, Smith JA. Pharmacologic therapy for cough. Curr Opin Pharmacol 2011;11: Pratter MR. Cough and the common cold: ACCP evidencebased clinical practice guidelines. Chest 2006;129(1 Suppl): 72S-74S. 7. Dicpinigaitis PV, Gayle YE. Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function. Br J Clin Pharmacol 2003;56: Bolser DC. Older-generation antihistamines and cough due to upper airway cough syndrome (UACS): efficacy and mechanism. Lung 2008;186 Suppl 1:S Mossad SB. Treatment of the common cold. BMJ 1998;317: Chung HS, Choi HK, Kim EM, Park MJ, Chung KH, Yoo YC. Demographic characteristics of zipeprol-associated deaths in Korea. Arch Pharm Res 1998;21: Schwartz RH. Adolescent abuse of dextromethorphan. Clin Pediatr (Phila) 2005;44: Allegra L, Bossi R. Clinical trials with the new antitussive levodropropizine in adult bronchitic patients. Arzneimittelforschung 1988;38: Luporini G, Barni S, Marchi E, Daffonchio L. Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer. Eur Respir J 1998; 12: Aversa C, Cazzola M, Clini V, Dal Negro R, Maiorano V, Tana F, et al. Clinical trial of the efficacy and safety of moguisteine in patients with cough associated with chronic respiratory diseases. Drugs Exp Clin Res 1993;19: Adams R, Hosie J, James I, Khong T, Kohn H, Smith I, et al. Antitussive activity and tolerability of moguisteine in patients with acute cough: a randomized double-blind placebo-controlled study. Adv Ther 1993;10: Dicpinigaitis PV, Gayle YE, Solomon G, Gilbert RD. Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough. Respir Med 2009;103: Dicpinigaitis PV, Gayle YE. Effect of guaifenesin on cough reflex sensitivity. Chest 2003;124: Dicpinigaitis PV, Spinner L, Santhyadka G, Negassa A. Effect of tiotropium on cough reflex sensitivity in acute viral cough. Lung 2008;186: Chung KF. Clinical cough VI: the need for new therapies for cough: disease-specific and symptom-related antitussives. Handb Exp Pharmacol 2009;(187): Jeyakumar A, Brickman TM, Haben M. Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. Laryngoscope 2006;116: Dicpinigaitis PV, Rauf K. Treatment of chronic, refractory cough with baclofen. Respiration 1998;65: Dicpinigaitis PV, Dobkin JB, Rauf K, Aldrich TK. Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist baclofen. J Clin Pharmacol 1998;38: Dicpinigaitis PV, Dobkin JB. Antitussive effect of the GABAagonist baclofen. Chest 1997;111: Mintz S, Lee JK. Gabapentin in the treatment of intractable idiopathic chronic cough: case reports. Am J Med 2006;119:e Lee B, Woo P. Chronic cough as a sign of laryngeal sensory neuropathy: diagnosis and treatment. Ann Otol Rhinol Laryngol 2005;114: Halum SL, Sycamore DL, McRae BR. A new treatment option for laryngeal sensory neuropathy. Laryngoscope 2009;119: Vol. 2, No. 4 Dec 2012 Korean J Fam Pract

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<303420C6AFC1FD20B1E8BBF3C8C62E687770> 대한내과학회지 : 제 78 권제 6 호 2010 특집 (Special Review) - 만성기침의진단과치료 진해거담제사용의실제 을지대학교을지병원내과 김상훈 Antitussives, mucolytic agents and expectorants in clinical practice Sang-Hoon Kim, M.D. Department of Internal Medicine,