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06/08/22 1 O O BAT BAT SISTEM SISTEM RESPIRASI RESPIRASI Yudi Purnomo, M.Kes, Apt Lab. Farmakologi Kedokteran PPD UNISMA

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Page 1: OBAT RESPI-1

04/21/23 1

OOBATBAT SISTEM SISTEM RESPIRASIRESPIRASI

Yudi Purnomo, M.Kes, AptLab. Farmakologi KedokteranPPD UNISMA

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MateriMateri

• Bronkodilator

• Nasal Decongesant

• Obat Batuk– Antitusif– Ekspektoran– Mukolitik

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Obat BronkodilatorObat Bronkodilator

• Digunakan Tx Asma ditandai episode Bronkospasme akut yg menyebabkan :

- Pernapasan singkat

- Sesak napas

- Batuk

- Mengi (wheezing)

- Pernapasan cepat

• Tujuan Tx : (-) gejala & cegah serangan 04/21/23 3

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Etiologi BronkospasmeEtiologi Bronkospasme

• Alergen

• Stress

• Suhu extrem

• Imbalance Kolinergik & Adrenergik

• Obstruksi saluran napas pd Asma selain bronkospasme e.c Inflamasi dinding bronkus & peningkatan sekresi mukus

04/21/23 4

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Mediator BronkospasmeMediator Bronkospasme

1. Spasmogen

- Histamin

- Leukotrien (LTC4, LTD4)

- Prostaglandin (PGD2)

- Platelet Activating Factor (PAF)

2. Kemotaksin

- LTB4

- PAF04/21/23 5

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BronkodilatorBronkodilator

1. Stimulan Beta-2 Adrenergik

2. Antagonis Muskarinik

3. Xanthin derivat

4. Antagonis LTD4

04/21/23 6

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BronkodilatorBronkodilator

1. Agonis Adrenergik Beta

- Epedrin

- Adrenalin (epinefrin)

- Salbutamol

- Terbutalin

-

2. Antagonis kolinergik

- Ipratropium bromida04/21/23 7

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BronkodilatorBronkodilator

3. Xanthin Derivat

- Teophilin

- Aminophilin

- Penthoxiphilin

4. Antagonis LTD4

- Montelukas

04/21/23 8

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EphedrinEphedrin

• Gol Amin simpatomimetik bekerja tak langsung, struktur ~ Norepinefrin (NE)

• Menggeser NE vesikular sitoplasma

• Efek ~ Epinefrin DOA> & Stimulasi SSP<

• Bekerja pada reseptor ß-1 & ß-2

• Efek ß-1 : ↑ TD, ↑ Frek & Kontr Jantung.

• Efek ß-2 : Relaksasi otot polos

• Efek alfa-1 : Vasokontriksi04/21/23 9

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EphedrinEphedrin

• Indikasi : Asma bronchiale, Bronchitis, Emphysema.

• Dosis : 3 dd 10-30 mg (p.o),

Child 3 dd 8-12,5 mg (p.o), 25-50 mg (s.c)

• Kontraindikasi : Hipertensi, Cardiac disorder, Glaukoma, Hipertiroid

• Efek samping : Takikardi, Aritmia, Retensi urine, Pembesaran Prostat

04/21/23 10

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Adrenalin (Epinefrin)Adrenalin (Epinefrin)

• Gol simpatomimetik bekerja langsung

• Agonis alfa-1 & 2 serta ß-1 & ß-2

• Tx. Status asmatikus

• Dirusak asam lambung Rute parenteral

• DOA pendek

• Dosis :

04/21/23 11

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SalbutamolSalbutamol

• Selektif ß-2 adrenergik merelaksasi otot polos bronkus melalui peningkatan cAMP yg mengaktifasi kinase.

• M’hambat pelepasan mast cell pulmonary

• M’rangsang pembersihan mukosiliar

• Efek thd ß-1 minimal (Ratio ß-2/ ß-1 >>)

• Indikasi : Bronkospasme

• K.I : Tirotoksikosis, Hipersensitif Salbutamol04/21/23 12

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SalbutamolSalbutamol

• Dimetabolisme di hati berkonjugasi dg sulfat, diekskresi dalam bentuk utuh

• T1/2 = 2,7-5 jam

• Dosis : 3 dd 1-4 mg (p.o)

• Rute : p.o, inhalasi, parenteral

• ESO : tremor, ketegangan saraf, takikardi bisa diatasi dg rute inhalasi

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Terbutalin Terbutalin

• Stimulan reseptor B-2 adrenergik selektif pada otot polos bronkus

• Meningkatkan klirens mukosilia PPOK

• Memperbaiki pengeluaran mukus kental

• DOA panjang

• Indikasi : Bronkospasme e.c asma bronkial, bronkitis kronik, emfisema

• K.I : hipersensitif simpatomimetik & tirotoksikosis04/21/23 14

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TerbutalinTerbutalin

• Rute pemberian : oral & parenteral

• Dosis : 3 dd 2,5 mg, max 15 mg/hari (p.o)

• ESO :

- Palpitasi & CV disorder <<

- Tremor pd lansia

- Headache

- Fatique

- Tinnitus04/21/23 15

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Ipratropium BromidaIpratropium Bromida

• Antagonis muskarinik Bloker asetilkolin

• Relaksasi otot polos bronkus yg efektif

• Bronkospasme ↓ akibat stimulasi histamin di respirasi tract

• Rute : Inhalasi

• Efek samping : ~ Atropin like drug seperti dilatasi pupil, penglihatan kabur, mulut kering, kesulitan berkemih, konstipasi

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TeophilinTeophilin

• Memiliki efek bronkodilatasi dg menghambat fosfodiesterase dan meningkatkan kadar cAMP selular mengurangi pelepasan histamin.

• Indikasi : Tx Bronkospasme

• C.I : Ulkus peptikum, renal & hepar disorder

• Rute : p.o dan parenteral

• Dosis : 3 dd 100-200mg04/21/23 17

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TeophilinTeophilin

• ESO :

- Mual,

- Sakit kepala,

- Insomnia

- Urinary freq

- Palpitasi

- Nervous

- Takikardi04/21/23 18

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TeophilinTeophilin

• Interaksi Obat :

- ↑ Stimulasi CNS dg Simpatomimetik

- ↑ kadar Teofilin dg Cimetidine,Alupurinol,

Eritromisin

- Antagonis efek Teofilin dg Beta blocker

- ↓ kadar Teofilin dg Rifampicin

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AminophilinAminophilin

• Bentuk ester/ garam Teophilin• Memiliki efek bronkodilator dg relakasasi

otot polos bronkus• Indikasi : Tx & Profilaksis spasme bronkus

yg berhubungan dg asma, emfisema• Dosis : 3 dd 100-300 mg• Kontra Indikasi : DM, tukak lambung,

Anak < 12 tahun• ESO : palpitasi, GIT disorder, Takikardi

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MontelukastMontelukast

• Antagonis Leukotrien bekerja ↓ bronkospasme & efek inflamasi LTD4

• Rute peroral

• Tx bronkospasme o.k pemberian Aspirin yg menginduksi asma akibat sintesa Leukotrien

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Nasal dekongestanNasal dekongestanSimpatomimetik Like DrugSimpatomimetik Like Drug

• Obat golongan Simpatomimetik :

- Efedrin

- Pseudoefedrin

- Fenilefrin

- Fenilpropanolamin

- Naphazolin

- Antazolin

- Oximetazolin (0,5 mg/ml ~ Illiadin)

- Xylometazolin (0,1 % ~ Otrivin)04/21/23 22

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MechanismeMechanismeSimpatomimetic DrugSimpatomimetic Drug

• Terkait NE release

• Pada Reseptor Beta Adrenergik :

- Bronkodilatasi

- ↑ Kontraksi & Frekuensi Jantung

- Relaksasi otot polos

- Glikogenolisis

• Pada Reseptor Alfa Adrenergik- Vasokontriksi, Midiasis, ↑ Sekresi

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ESO ESO Simpatomimetik Like Simpatomimetik Like

• chest pain or irregular heartbeats;

• increased blood pressure;

• agitation, hostility, or personality changes;

• thoughts of suicide

• pain or difficulty passing urine;

• rapid or troubled breathing;

• Alergic Rx

04/21/23 24

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IntroIntro Obat Batuk Obat Batuk

BATUKBATUK : Reflek fisiologis dalam keadaan sehat/ sakit yang ditimbulkan oleh berbagai sebab

PenyebabPenyebab : Rangsangan selaput lendir pernafasan

Fungsi batukFungsi batuk : mengeluarkan & membersihkan saluran nafas dari zat rangsangan asing & zat infeksi ( mekanisme perlindungan )

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EtiologiEtiologi Batuk Batuk

PenyebabPenyebab batuk batuk :1. Radang : infeksi (virus, tifus, radang paru,

cacing, TBC)2. Mekanis (asap rokok, debu, tumor)3. Perubahan suhu udara4. Rangsang kimia (bau, gas)5. Penyakit jantung6. Psikis

Prinsip terapiPrinsip terapi :• Cari penyebabnya (etiologi) • Simptomatik

DahakDahak senyawa kompleks

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PenggolonganPenggolongan Batuk Batuk

Dibedakan :I. BATUK PRODUKTIF• Mekanisme perlindungan untuk mengeluarkan

zat asing (kuman, debu) dan dahak• Prinsip : tak boleh ditahan

PENGOBATAN1. Uap air (mendidih) yang dihirup memperbanyak jumlah sekret- terutama untuk batuk dalam- minum air banyak

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PenggolonganPenggolongan Batuk Batuk

2. Emolliensia : memperlunak rangsangan batuk,memperlicin

tenggorok3. Ekspektoransia : mencairkan dahak,

mempermudah pengeluaran4. Mukolitik : mencairkan dahak

II. BATUK NON PRODUKTIF Kering (tanpa dahak) Pengeluaran tak mungkin : tumor Batuk tak bermanfaat Obat menekan rangsangan batuk

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TerapiTerapi Batuk BatukPENGOBATAN1. Zat pereda (Cough Suppresan = Antitusif)

- Kerja sentral : kodein, noskapin,dekstrometorfan - Tanpa kerja sentral : benzonatat & dibunat

2.Antihistamin - Efek sedatif kombinasi dengan obat batuk lain- misal : prometazin, difenhidramin, d-klorfeniramin

3.Anestesi lokal Menghambat penerusan rangsangan batuk ke pusat batuk, misal : benzonatat, pentoksiverin

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TerapiTerapi Batuk Batuk

Menurut titik kerjanya :A. ZAT – ZAT SENTRAL (Cough Supresant) Menekan rangsang batuk di pusat batuk

(medulla, otak) Zat adiktif : candu (opii, doveri), kodein Non adiktif : noskapin, dekstrometorfan, pentoksiverin

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TerapiTerapi Batuk Batuk

B. ZAT PERIFER : kerja diluar SSP

o Ekspektoransia : kerja reflek di lambung yang merangsang batuk, sekresi dahak bersifat cair diperbanyak

o Mukolitika : menurunkan viskositas dahak, efektif pada dahak kental

o Antitusif: menghambat reseptor sensibel di

saluran nafas shg rangsangan batuk berkurang

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TerapiTerapi Batuk Batuk

ExpectorantsExpectorants• Potassium iodide• Guaifenesin • Ipecacuanha • Creosote• Guaiacolsulfonate

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TerapiTerapi Batuk Batuk

MucolyticsMucolytics• Acetylcysteine• Bromhexine • Carbocisteine • Ambroxol • Erdosteine

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TerapiTerapi Batuk Batuk

Antitusif (Antitusif (Cough suppressantsCough suppressants) ) ::

Opium alkaloids and derivativesOpium alkaloids and derivativeso Ethylmorphine o Dextromethorphano Hydrocodone o Codeine o Noscapine

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COUGH SUPPRESANTS COUGH SUPPRESANTS examplesexamples

KodeinDextromethorphanNoskapinPentoksiverinBenzonatatOksolaminDibunatTipepidinHydrocodone

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KodeinKodein

KODEIN

Chemical data

Formula C18H21NO3 

Mol. mass299.364 g/mol

Systematic (IUPAC) name

7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-

6-ol

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KodeinKodein

• Sifat menyerupai morfin (efek analgetik, anti diare & pereda batuk lebih lemah)

• Dijumpai dalam bentuk Codein fosfat & Codein Sulfat• Biasa dikombinasi dengan asetosal, membebaskan

histamin• Absorbsi lebih baik dari morfin, IV tak dianjurkan • Anak kecil dapat terjadi konvulsi,depresi pernafasan• Harus dengan resep dokter Apotek• Dapat menyebabkan adiksi lebih lemah dari Morfin• Dosis : po 3-5 dd 10-40 mg, max 200 mg

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KodeinKodein

Adverse effectsAdverse effectsCommon adverse drug reactions associated withthe use of codeine include :

- euphoria - nausea- Itching- vomiting

- dry mouth - constipation - orthostatic hypotension- urinary retention

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DextromethorpanDextromethorpan

Systematic (IUPAC) name

((+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan)

Chemical data

Formula C18H25NO 

Mol. mass 271.4 g/mol

Pharmacokinetic data

Bioavailability 11%[1]

Metabolism

Hepatic (liver) enzymes

Half life 1.4–3.9 hours

Excretion Renal

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DextromethorpanDextromethorpan

DEKSTROMETORFAN• Struktur mirip kodein• Daya menekan batuk = kodein, tak ada efek

analgetik, adiktif (-) , obstipasi (-)• Mudah diabsorpsi & dimetabolisme 15-60 menit• DOA DMP HBr ~ 3-8 jam • ES : ringan,rasa kantuk ringan, mual• Dosis : po 3-4 dd 10-20 mg pc; anak 2-6 th :3-4

dd 8mg; 6-12 th 3-4 dd 15 mg

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DextromethorpanDextromethorpan

Side-effectsSide-effectsSide-effects of dextromethorphan use can include rash/itching, disassociation,

nausea as well as other gastrointestinal disturbances,

drowsiness, dizziness, excitation, vomiting, blurred vision, dilated pupils, sweating, fever, hypertension, shallow respiration, diarrhea, urinary retention, and increases in heart rate, blood pressure, and body temperature

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NoskapinNoskapin

Noscapine

Systematic (IUPAC) name

(3S)- 6,7-Dimethoxy-3-((5R)-5,6,7,8 - tetrahydro-4-methoxy-6-methyl-1,3-

dioxolo(4,5-g) isoquinolin -5-yl)- 1(3H)-isobenzofuranone

Chemical data

Formula C22H23NO7 

Mol. mass 413.421

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NoskapinNoskapin

• Efek pereda batuk tak sekuat kodein, tak mengakibatkan depresi pernafasan & obstipasi

• Efek adiksi ringan : banyak dipakai• Tak bersifat analgetik,membebaskan histamin• Efek samping jarang• Dosis : po 3-4 dd 15-50 mg, max 250 mg

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PentoksiverinPentoksiverin

Systematic (IUPAC) name

2-(2-diethylaminoethoxy)ethyl 1-phenylcyclopentane-1-carboxylate

Chemical data

Formula C20H31NO3 

Mol. mass 333.465 g/mol

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PentoksiverinPentoksiverin

PENTOKSIVERIN• Pereda batuk sentral, anestetik lokal &

spasmolitik• 1½ kali lebih kuat dari kodein• ES ringan• Laktasi tidak boleh bayi sesak napas • Dosis tinggi : resiko adiksi• Dosis : lihat buku

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PentoksiverinPentoksiverin

• Pentoxyverine (rINN) or carbetapentane is a cough suppressant

• It is sold over-the-counter in the United States, usually in combination with other medications, especially decongestants

• It is commonly used for cough associated with illnesses like common cold

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BenzonatatBenzonatat

Systematic (IUPAC) name

2-[2-[2-[2-[2-[2-[2-[2- (2-methoxyethoxy) ethoxy] ethoxy] ethoxy] ethoxy] ethoxy] ethoxy]

ethoxy] ethyl4-butylaminobenzoate

Chemical data

Formula C30H53NO11 

Mol. mass603.742 g/mol

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BenzonatatBenzonatat

BENZONATATBENZONATAT• Sebagai pereda batuk : berdasar efek

anestetik lokal & penghambatan reseptor di saluran nafas

• Dibanding kodein lebih lemah• ES : ringan sekali

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BenzonatatBenzonatat

• Benzonatate is a medication taken orally to suppress coughs

• Benzonatate is a non-narcotic oral antitussive (cough suppressant) drug which works by anesthetizing the tissues of the lungs and pleura responsible for the cough reflex

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TipepidinTipepidin

Tipepidine

Systematic (IUPAC) name

3-(dithiophen-2-ylmethylidene)-1-methyl-piperidine

Chemical data

Formula C15H17NS2 

Mol. mass275.434 g/mol

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EKSPEKTORANS EKSPEKTORANS examplesexamples

Ammonium klorida

Kalium iodida

Kreosot

Guaifenesin/ gliseryl guaciolat

Ipecacuanhae radix

Althea root

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Amonium kloridaAmonium klorida

AMONIUM KLORIDA• Garam berdaya diuretik lemah (ACIDOSIS/

kelebihan asam dalam darah) merangsang pusat nafas

frekuensi nafas meningkat

pergerakan cilia meningkat• OBH• ES : dosis tinggi asidosis, gangguan lambung

(mual, muntah)

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Kalium iodidaKalium iodida

Potassium iodide

IUPAC name Potassium iodide

Othernames

Kalium iodide,knollide, potide

Properties

Molecular formula KI

Molar mass 166.00 g/mol

Appearancewhite crystalline

solid

Density 3.13 g/cm3, solid

Melting point 681 °C (954 K)

Boiling point 1330 °C (1603 K)

Solubility in water128 g/100 ml (6

°C)

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Kalium iodidaKalium iodida

• KI (Kalium iodida)• Iodida : menstimulasi sekresi cabang

tenggorok & mencairkan dahak, sebagai obat batuk kurang efektif

• Antiseptik pada Px Shore throat• Ekspektorant pada Px Lung Congestion• Profilaksis dan terapi struma, hipertirosis,

tetes mata pada katarak• Dosis : lihat buku

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KreosotKreosot

KREOSOT• Menyuling kayu (eropa), mengandung 70%

guaiacol & 30% kreosot • Sebagai ekspektoran kurang efektif• Bau tak enak, merangsang mukosa lambung

dipilih guaiacolkarbonat • Guaifenesin (gliserilguaiakolat) : banyak

dipakai campuran obat batuk merelaksasi otot

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KreosotKreosot

• Creosote is the name used for a variety of products: wood creosote, coal tar creosote

• Wood creosote has been used as a disinfectant, a laxative, and a cough treatment, but these have mostly been replaced by newer medicines

• Coal tar products are used in medicines to treat skin diseases such as psoriasis, and also as animal and bird repellents, insecticides, animal dips, and fungicides

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Guaifenesin (GG)Guaifenesin (GG)

Systematic (IUPAC) name

3-(2-methoxyphenoxy)propane-1,2-diol

Chemical data

Formula C10H14O4 

Mol. mass198.216 g/mol

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GuaifenesinGuaifenesin

• Guaifenesin guaiphenesin is an expectorant drug usually taken orally to assist the expectoration ("bringing up") of phlegm from the airways in acute respiratory tract infections

• It is also called gliseryl guaicolatgliseryl guaicolat

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GuaifenesinGuaifenesin

UsesUses

Treatment of coughing• Guaifenesin is frequently combined with

dextromethorphan, an antitussive

• Under normal circumstances this combination

leads to fewer, but more productive coughs

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GuaifenesinGuaifenesin

Treatment of asthma

• Guaifenesin is effective in the treatment of the thickened bronchial mucosa characteristic of asthma

• It works by drawing water into the bronchi. The water both thins mucus and lubricates the airway, facilitating the removal of mucus by coughing

• One may notice a sense of dry mouth when taking this medication. Water consumption is important, not only to help with dry mouth, but also to improve the effectiveness of the drug

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Ipecacuanhae RadixIpecacuanhae Radix

Ipecacuanha

Scientific classification

Binomial name

Psychotria ipecacuanha

Kingdom: Plantae

Division: Magnoliophyta

Class: Magnoliopsida

Order: Rubiales

Family: Rubiaceae

Genus: Psychotria

Species: P. ipecacuanha

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Ipecacuanhae RadixIpecacuanhae Radix

• Ipecacuanha (Psychotria ipecacuanha) of family Rubiaceae is a flowering plant, the root of which is most commonly used to make syrup of ipecac, a powerful emetic

• Ipecacuanha is useful as an emetic when it is necessary to unload the stomach in cases where there is great debility or in childhood.

• As a nauseant, expectorant, and diaphoretic, it is prescribed in bronchitis, etc., and in disorders in which it is desired to increase the actions of the skin

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Althea rootAlthea root

Marshmallow (Althaea officinalis)

Scientific classification

Kingdom:

Plantae

Division:

Magnoliophyta

Class: Magnoliopsida

Order: Malvales

Family: Malvaceae

Genus: AlthaeaL.

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Althea rootAlthea root

• The root contains starch (37%), mucilage (11%), pectin (11%), flavonoids, phenolic acids, sucrose, and asparagine

• In herbalism mallow is used as a gargle to treat mouth and throat ulcers

• It is also useful for gastric ulcers• The flowers and young leaves can be eaten.

They are often added to salads or boiled and fried

• Also used in cosmetics for the skin

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MUCOLYTICS MUCOLYTICS examplesexamples

• Asetil sistein

• Bromheksin

• Carbosisteine

• Ambroksol

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Asetil sisteinAsetil sistein

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Asetil sisteinAsetil sistein

ASETIL SISTEIN Memperpendek rantai panjang mukoprotein dari

dahak shg lebih cair mudah dikeluarkan Antioksidan (karbosistein,mesna -) Memperbaiki gerakan cilia Khasiat antibiotik diperkuat (doksisiklin,

minosiklin) Antidotum intoksikasi parasetamol ES : mual, muntah Tak merugikan janin & boleh dimakan ibu hamil

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BromheksinBromheksin

Systematic (IUPAC) name

2,4-dibromo-6-{[cyclohexyl(methyl)amino]meth

yl}aniline

Chemical data

Formula C14H20Br2N2 

Mol. mass 376.13

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BromheksinBromheksin

BROMHEKSIN• Berdaya mukolitik pd dosis yg cukup tinggi,

depolimerasi serat mukopolisakarida• Tx ggn respirasi akibat produksi mukus yang

kental & berlebihan• Onset of action ± 5 jam (oral), inhalasi 15’ • Menstimulasi gerakan cilia di bronki• Meningkatkan kadar AB dalam dahak• Ambroksol, metabolit

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KarbosisteinKarbosistein

Systematic (IUPAC) name

2-amino-3-(carboxymethylsulfanyl)propano

ic acid

Chemical data

Formula C5H9NO4S 

Mol. mass179.195 g/mol

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KarbosisteinKarbosistein

Carbocisteine is a mucolytic that can be used to help relieve the symptoms of Chronic Obstructive Pulmonary Disorder COPD and bronchiectasis by allowing the sufferer to bring up sputum more easily

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AmbroxolAmbroxol

o Dijumpai dalam bentuk garam Ambroxol HCl• Mukolitik agent yang memudahkan pengeluaran

mukus yang kental dari sistem respirasi• Tx : Akut & kronik respirasi diseases, chronic

bronchitis exacerbation, bronchitic asthmatic• Efek Samping : Ggn GIT ringan, Rx Alergi, Skin

rash, fever• Pemberian bersamaan dg Antibiotik dapat

meningkatkan kadar Antibiotik di jaringan paru• Dosis : 3 dd 30 mg (dws) , 3 dd 15 mg (6-12 th)

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ErdosteineErdosteine

• Mukolitik agent

• Struktur memiliki gugus sulfur yang berperan sebagai Antibakterial

• CI : Sirosis hepatik, gagal ginjal

• Dosis 2-3 dd 300 mg (dws)

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HerbaHerba

Obat batuk dari herba

• Jeruk keprok

• Grindelia

• Lemon dll