Penyakit Paru Obstruktip Kronis(PPOK)3 penyakit utama tergolong PPOK:Asma bronkhialeBronkhitis kronisEmfisema pulmonum

Asma bronkialGambaran klinik asma bronkial: dikeluarkannya senyawa autacoids yang mempengaruhi saluran paru mulai dari bronkus sampai alveolus dgn akibat a.l.: sesak nafas, dgn gambaran paru sbb: Bronkokonstriksi Inflamasi &edema mukosa bronkus dan jaringan sekitarnya Hipersekresi kelenjar mukosa bronkus

BRONKO-KONSTRIKSIOtot polos :Kontraksi sebabkan bronchospasmushypertrophy

Beta agonists Endogenous norepinephrine can stimulate alpha-1, alpha-2, beta-1 and beta-2 receptors. Most drugs are created to be either agonists or antagonists that are more selective for one or two receptors. However, no substance so far has shown 100% selectivity. Beta agonist agents are more selective for the beta receptors. Beta-1 receptors are abundant in the circulation and skeletal muscle, beta-2 in smooth muscle (particularly in the respiratory tree).Commonly used drugs of this group are ephedrine, salbutamol, salmeterol, and terbutaline.

Anticholinergic effects in the lungVagal stimulation of the respiratory tract's muscarinic-2 receptors causes airway constriction. By blocking this parasympathetic stimulation, the anticholinergic agents reduce smooth muscle tone and lead to dilatation of the constricted airway. There are three principle muscarinic (M) receptors: M1=postganglionic and CNS, M2=postsynaptic in heart nodes and myocardia, and M3=postsynaptic in smooth muscle, vascular endothelium and secretory glands. The M4 stimulates molecular mechanisms like the M2 receptors but its function is unclear. The M5 receptor is like the M1 receptor and is also found in the CNS, but its role is elusive.

Anticholinergics Despite their commonly used name, the anticholinergic drugs antagonize only the muscarinic receptors.Ipratropium and tiotropium are the two anticholinergics (or parasympatholytics) currently used. Both are only available for administration via the inhalational route. Ipratropium (the older drug) has no selectivity for M1, M2, or M3 receptors and lasts for about 6 hours. However, tiotropium is a long-acting anticholinergic which can be used once daily. Anticholinergic drugs also effect mucus secretion. Since systemic anticholinergic drugs can block all muscarinic receptors, tachycardia, increased contractility, blurred vision, dry mouth, decreased sweating, constipation, and confusion are effects that can be expected in a dose dependent manner.

Inflammasi pada asma : - increase in number of inflammatory cells - edema - dilated blood vessels - excessive mucus

Antigen trigger on mast cell The membrane of mast cells has Fc receptors for specific IgE molecules. The IgE molecules get attached to the mast cell when it is bound with an antigen. The IgE-Fc receptor binding triggers: the degranulation process (releasing histamine, proteases, TNF and interleukins) the increased synthesis of interleukins the release of leukotrienes as well as prostaglandins.

Mast cell stabilizers Antihistamines block the effects of histamine already released into the system. Another means of blocking the effects of histamine is by preventing it's release from inflammatory cells. Nedocromil and cromoglycate are substances that are thought to work by preventing degranulation of mast cells. These agents are only available by inhalation and are indicated for the prophylaxis of mild asthma. Unfortunately, poor clinical results with these agents limit their utility.

Inhaled steroids (beclometason and fluticason) are commonly used as first line treatment for the prophylaxis to reduce the chronic inflammation in asthmatic patients. Short pulse of systemic steroids are sometimes used to treat an acute exacerbation in an asthmatic patient. These short pulses should never exceed two weeks in order to avoid serious toxicities. If the respiratory patient requires chronic systemic steroids in order to reduce symptoms, the clinician should repeatidily try a slow taper to the lowest tolerated dose.

Mucolytic agentsMucus is largely composed of glycoproteins. These are large molecules containing several disulfide bridges. Mucolytic agents are sulfur compounds (acetylcysteine) such as N-acetylcysteine that break up the disulfide bridges making the molecules smaller and the mucus more viscous. They act mainly when applied directly by inhalation or during bronchoscopy.Their effectiveness when used orally is doubtful.Completely different from sulfur compounds is DNAse (not shown), which cleaves long DNA molecules. In cystic fibrosis (CF), inflammatory cells are abundant in the airway lumen and their DNA is released after degradation. The long molecules make the mucus very sticky. DNAse is often very effective in CF making the sputum watery within a short time. DNAse is not beneficial to all CF patients however.

Submucosal glands are activated by vagal stimulation. There is no sympathetic innervation

Anticholinergics for mucusAnticholinergic agents in theory will reduce mucus production. This could inadvertently lead to a more sticky secretion in chronic bronchitis and CF patients. However in vivo studies point out that this anticholinergic activity is clinically rather unimportant. Nevertheless some patients do experience some dryness of mouth or throat after inhalation of ipratropium

Late inflammatory mediators Many different cells respond to an antigen trigger in an allergic asthma response. Prostaglandins, interleukins, LTB4 and LTC4 have several actions in inflammation, and many of these substances are chemo-attractants. The increased proliferation of these cells leads to the long-term tissue changes seen in chronic asthma

Leukotriene modifiersThere are two types of agents that modify leukotriene response, inhibitors of LT synthesis that block lipo-oxygenase, and LT receptor antagonists. The drugs zafirlukast and montelukast belong to the latter group and are used more clinically.Zileuton is an inhibitor of leukotriene synthesis In theory, these LT modifying agents could have a major role in the treatment of asthma. However theory and practice are not identical; many asthmatics appear not to have any benefit from LT modifiers, which now are prescribed mainly for mild asthma or asthma with profound exercise-induced symptoms.

Terapi thd asma bronkialBronkodilatatorObat thd inflamasi dan edema mukosa Mengurangi sekret (yang berlebihan)Mengatasi hipoxiaTindakan supportip lainnya:cairan ,dsb

Macam-macam obat asma :SimpatomimetikaDerivat xanthine: theofilin,aminofilinKortikosteroid.Biskromones: kromolyn, ketotifen.Antikolinergik:ipratropium bromide. Semua obat tersebut diatas utk terapi initial ataupun pencegahan.

Terapi penunjangAntibiotikaOksigen, cairan I.V.Mukolitika-mukokinetika: fisioterapi, ambroxol, asetilsistein( Efektivitas kedua obat ini dicabang bronkus diragukan).

BronkodilatatorSimpatomimetika:adrenalin, beta-2 agonist, efedrin.Derivat xanthine: teofilin,aminofilin

Adrenaline Diberikan s.c. dosis kecil 0,2 ml larutan 1:1000 untuk mengatasi serangan akut.Efek samping takikardi, hipertensi dan yg berbahaya bila terjadi aritmia ventrikuler (fatal).

Beta-2 agonistTermasuk golongan ini ialah: salbutamol(albuterol), metaproterenol, ritodrine,terbutaline, fenoterol dll.Golongan ini dapat digunakan per oral, parenteral,dan per inhalasional.Efek samping berupa takikardi, hipertensi dan aritmia

Derivat xanthineTheophylline,aminophylline merupakan antagonist thd reseptor adenosine dan mencegah pemecahan cAMP dan cGMP.Diberikan i.v. atau per-oral.Efek samping:per oral,mual; i.v. terlalu cepat dpt depressi jantung.Dosis besar konvulsi.Index terapi kecil.

Theophylline Theophylline is a phosphodiesterase inhibitor, which gives rise to higher intracellular levels of PKA and PKG. The increase in PKA and PKG activity is associated with smooth muscle relaxation and decreased inflammatory responses. Theophylline is also considered a last-line agent due to its pharmacokinetic parameters which give it a narrow therapeutic window between effectiness and toxicity.

KortikosteroidsGlukokorticoids: prednisone, dexamethasone, prednisoloneAnti-inflamatorik.Prednisolone long-acting, banyak efek samping dibanding short -acting: prednisone ,dexamethasone.Diberikan sistemik oral atau parenteral. Inhalasi lebih efektip (efek samping candidiasis)Preparat a.l. Beclomethasone dipropionate.

Sodium cromoglycate,ketotifenMekanisme kerja tidak diketahui dengan pasti, diduga menghambat pelepasan spasmogens dari sel-sel radang.Hanya untuk pencegahan.Bisa per-inhalational (cromoglycate), sering memicu batuk.Tidak mengganggu pertumbuhan,baik untuk anak-anak.

AntikolinergikIpratropium bromide, merupakan derivat atropin dengan gugus amine-quarterner.Diberikan per-inhalasional berupa aerosol;bermanfaat lebih-lebih untuk menekan produksi sekret bronkus. Absorpsi oleh mukosa minimal. Diindikasikan terutama pada bronkitis- kronis dengan gejala asmatis.

MANAGEMENT OF ACUTE ASTHMAThe treatment of acute attacks of asthma in patients reporting to the hospital requires more continuous assessment and repeated objective measurement of lung function. For patients with mild attacks, inhalation of beta-receptor agonist is as effective as subcutaneous injection of epinephrine. Both of these treatments are more effective than intravenous administration of aminophylline. Severe attacks require treatment with oxygen, frequent or continuous administration of aerosolized albuterol, and systemic treatment with prednisone or methylprednisolone (0.5 mg/kg every 6 hours). Even this aggressive treatment is not invariably effective, and patients must be watched closely for signs of deterioration. Intubation and mechanical ventilation of asthmatic patients cannot be undertaken lightly but may be lifesaving if respiratory failure supervenes.

Sympathomimetics Used in AsthmaAlbuterol (generic, Proventil, Ventolin, others)Inhalant: 90 g/puff aerosol; 0.083, 0.5% solution for nebulizationOral: 2, 4 mg tablets; 2 mg/5 mL syrupOral sustained-release: 4, 8 mg tabletsAlbuterol/Ipratropium (Combivent, DuoNeb)Inhalant: 103 g albuterol + 18 g ipratropium/ puff; 3 mg albuterol + 0.5 mg ipratropium/3 mL solution for nebulizationBitolterol (Tornalate)Inhalant: 0.2% solution for nebulizationEphedrine (generic)Oral: 25 mg capsulesParenteral: 50 mg/mL for injectionEpinephrine (generic, Adrenalin, others)Inhalant: 1, 10 mg/mL for nebulization; 0.22 mg epinephrine base aerosolParenteral: 1:10,000 (0.1 mg/mL), 1:1000 (1 mg/mL)

Formoterol (Foradil)Inhalant: 12 g/puff aerosol; 12 g/unit inhalant powderIsoetharine (generic)Inhalant: 1% solution for nebulizationIsoproterenol (generic, Isuprel, others)Inhalant: 0.5, 1% for nebulization; 80, 131 g/puff aerosolsParenteral: 0.02, 0.2 mg/mL for injectionLevalbuterol (Xenopex)Inhalant: 0.31, 0.63, 1.25 mg/3 mL solutionMetaproterenol (Alupent, generic)Inhalant: 0.65 mg/puff aerosol in 7, 14 g containers; 0.4, 0.6, 5% for nebulizationPirbuterol (Maxair)Inhalant: 0.2 mg/puff aerosol in 80 and 300 dose containersSalmeterol (Serevent)Inhalant aerosol: 25 g salmeterol base/puff in 60 and 120 dose containersInhalant powder: 50 g/unitSalmeterol/Fluticasone (Advair Diskus)Inhalant: 100, 250, 500 g fluticasone + 50 g salmeterol/unitTerbutaline (Brethine, Bricanyl)Inhalant: 0.2 mg/puff aerosolOral: 2.5, 5 mg tabletsParenteral: 1 mg/mL for injection

Aerosol Corticosteroids Beclomethasone (QVAR, Vanceril)Aerosol: 40, 80 g/puff in 200 dose containersBudesonide (Pulmicort)Aerosol powder: 160 g/activationFlunisolide (AeroBid)Aerosol: 250 g/puff in 100 dose containerFluticasone (Flovent)Aerosol: 44, 110, and 220 g/puff in 120 dose container; powder, 50, 100, 250 g/activationFluticasone/Salmeterol (Advair Diskus)Inhalant: 100, 250, 500 g fluticasone + 50 g salmeterol/unitTriamcinolone (Azmacort)Aerosol: 100 g/puff in 240 dose container

Leukotriene InhibitorsMontelukast (Singulair)Oral: 10 mg tablets; 4, 5 mg chewable tablets; 4 mg/packet granulesZafirlukast (Accolate)Oral: 10, 20 mg tabletsZileuton (Zyflo)Oral: 600 mg tablets

Cromolyn Sodium & Nedocromil SodiumCromolyn sodiumPulmonary aerosol (generic, Intal): 800 g/puff in 200 dose container; 20 mg/2 mL for nebulization (for asthma)Nasal aerosol (Nasalcrom):* 5.2 mg/puff (for hay fever)Oral (Gastrocrom): 100 mg/5 mL concentrate (for gastrointestinal allergy)Nedocromil sodium (Tilade)Pulmonary aerosol: 1.75 mg/puff in 112 metered-dose container*OTC preparation.

Methylxanthines: Theophylline & DerivativesAminophylline (theophylline ethylenediamine, 79% theophylline) (generic, others)Oral: 105 mg/5 mL liquid; 100, 200 mg tabletsOral sustained-release: 225 mg tabletsRectal: 250, 500 mg suppositoriesParenteral: 250 mg/10 mL for injectionTheophylline (generic, Elixophyllin, Slo-Phyllin, Uniphyl, Theo-Dur, Theo-24, others)Oral: 100, 125, 200, 250, 300 mg tablets; 100, 200 mg capsules; 26.7, 50 mg/5 mL elixirs, syrups, and solutionsOral sustained-release, 812 hours: 50, 60, 75, 100, 125, 130, 200, 250, 260, 300 mg capsulesOral sustained-release, 824 hours: 100, 200, 300, 450 mg tabletsOral sustained-release, 12 hours: 100, 125, 130, 200, 250, 260, 300 mg capsulesOral sustained-release, 1224 hours: 100, 200, 300 tabletsOral sustained-release, 24 hours: 100, 200, 300 mg tablets and capsules; 400, 600 mg tabletsParenteral: 200, 400, 800 mg/container, theophylline and 5% dextrose for injection

Other MethylxanthinesDyphylline (generic, other)Oral: 200, 400 mg tablets; 33.3, 53.3 mg/5 mL elixirParenteral: 250 mg/mL for injectionOxtriphylline (generic, Choledyl)Oral: equivalent to 64, 127, 254, 382 mg theophylline tablets; 32, 64 mg/5 mL syrupPentoxifylline (generic, Trental)Oral: 400 mg tablets and controlled-release tabletsNote: Pentoxifylline is labeled for use in intermittent claudication only.

Antimuscarinic Drugs Used in AsthmaIpratropium (generic, Atrovent)Aerosol: 18 g/puff in 200 metered-dose inhaler; 0.02% (500 g/vial) for nebulizationNasal spray: 21, 42 g/spray