Tiotropium pada COPD

Tiotropium pada COPD

Definisihambatan aliran udara yang tidak sepenuhnya reversibelbersifat progresifrespon inflamasi paru terhadap gas atau partikel yang berbahaya (noxious)GOLD 2011Buka hambatan aliran udara yang reversibel sebagian (partially reversible) tapi MENETAP (persistent)

Global Strategy for Diagnosis, Management and Prevention of COPDRisk Factors for COPDGenesInfectionsSocio-economic statusAging Populations 2014 Global Initiative for Chronic Obstructive Lung Disease4PatogenesisOxidative stressImbalance of proteinases and anti-proteinasesInflamasi kronis

Inflammatory cells :Macrophages leukotriene B4T-lymphocytes (CD8) interleukin 8Neutrophils TNF- Mechanisms Underlying Airflow Limitation in COPD

Small Airways DiseaseAirway inflammationAirway fibrosis, luminal plugsIncreased airway resistanceParenchymal DestructionLoss of alveolar attachmentsDecrease of elastic recoilAIRFLOW LIMITATION 2014 Global Initiative for Chronic Obstructive Lung Disease7SYMPTOMS chronic coughshortness of breathEXPOSURE TO RISKFACTORS tobaccooccupationindoor/outdoor pollutionSPIROMETRY: Required to establish diagnosisGlobal Strategy for Diagnosis, Management and Prevention of COPDDiagnosis of COPD sputum 2014 Global Initiative for Chronic Obstructive Lung Disease8Global Strategy for Diagnosis, Management and Prevention of COPDClassification of Severity of Airflow Limitation in COPD*In patients with FEV1/FVC < 0.70:

GOLD 1: Mild FEV1 > 80% predicted GOLD 2: Moderate 50% < FEV1 < 80% predicted

GOLD 3: Severe 30% < FEV1 < 50% predicted

GOLD 4: Very Severe FEV1 < 30% predicted

*Based on Post-Bronchodilator FEV1 2014 Global Initiative for Chronic Obstructive Lung Disease9Global Strategy for Diagnosis, Management and Prevention of COPDManage Stable COPD: Pharmacologic Therapy(Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.)PatientRecommendedFirst choiceAlternative choiceOther PossibleTreatmentsASAMA prnor SABA prnLAMA orLABA orSABA and SAMATheophyllineBLAMA or LABALAMA and LABASABA and/or SAMATheophyllineCICS + LABAor LAMA

LAMA and LABA orLAMA and PDE4-inh. orLABA and PDE4-inh.

SABA and/or SAMATheophyllineDICS + LABAand/or LAMA

ICS + LABA and LAMA or ICS+LABA and PDE4-inh. orLAMA and LABA orLAMA and PDE4-inh.CarbocysteineSABA and/or SAMATheophylline10PatientFirst choiceAlternative choiceOther Possible Treatment **ASAMA prnor SABA prnLAMA orLABA orSABA and SAMATheophyllineBLAMA or LABALAMA and LABASABA and/or SAMATheophyllineCLAMAorICS + LABA

LAMA and LABA or LAMA and PDE4-inh or LABA and PDE4-inh SABA and/or SAMATheophyllineDLAMAand/or ICS + LABA

ICS + LABA and LAMA or ICS+LABA and PDE4-inh. orLAMA and LABA or LAMA and PDE4-inh. CarbocysteineSABA and/or SAMATheophyllineGOLD Updated 2014Global Strategy for Diagnosis, Management and Prevention of COPDManage Stable COPD: Pharmacologic Therapy

LAMA in Every Patients GroupMost of GOLD Recommendations on the use of LAMA comes from Trials with Tiotropium** Medications in this column can be used alone or in combination with other options in the Recommended First Choice and Alternative Choice columns11Tiotropium BromidaAntagonist Receptor Muscarinic Long ActingBersifat sintetis, sedikit larut dalam air dan larut dalam metanolRumus molekul :C19 H22 No4 S2 Br H2ODaya serap rendah efek samping lebih sedikitWaktu paruh 24 jam

Mekanisme kerja3 reseptor muskarinik M1 Gangglion parasimpatisM2 Ujung postgangglion kolinergikM3 Otot dan kelenjar submukosa

Tiotropium saraf parasimpatis (M1) relaksasi otot polos saluran napas melalui antagonis dari asetilkolin reseptor muskarinik M3 pada otot polos saluran napas bronkodilatasi

Metabolisme dan ekskresi : ginjal urineIndication Based on severity Moderate COPDSevere COPD

KontraindikasiEksaserbasi Hipersensitivitas Tiotropium, atropin atau turunannyaPenyakit jantungHamil dan menyusui

Maintenance therapy with long-acting bronchodilators is key to managing COPD

Bronchodilators have been shown to have beneficial effects on:18BronchodilatorsSymptomsQuality of lifeExacerbations (sudden worsening)

COPD, chronic obstructive pulmonary diseaseFerro TJ. Clin Pulm Med 2005;12(4 Suppl):S13-S15; Decramer M. Eur Respir Rev 2006;15(99):51-57.Exercise (daily activity)Lung function18Tiotropium is available in two devices : HandiHaler and Respimat Respimat SMI HandiHaler1. SPIRIVA Local Product Information 2011; 2. SPIRIVA Respimat Local Product Information 2011The Respimat is a new-generation, propellant-free inhaler, an innovative approach to inhalation therapyPatients can choose between single- and multidose devicePatients can choose between HandiHaler or Respimat Both devices well established in most countries with HandiHaler being the most prescribed COPD maintenance drug device worldwide

19Key pointsA major advantage of tiotropium therapy for chronic obstructive pulmonary disease (COPD), is that patients have the choice of two alternative devices: the single-dose HandiHaler (dry powder inhaler)1 or the multi-dose Respimat (Soft Mist inhaler [SMI]).2 Both devices are well established in most countries, and HandiHaler is the most prescribed COPD maintenance drug device worldwide (with more than 25 million patient-years of use).3 It is a dry powder inhalation capsule, approved for use in over 100 countries worldwide, with market introduction in Europe in 2002 and, subsequently, in other countries including the United States (approval in 2004). Tiotropium Respimat SMI 5 g once daily is an inhalation solution delivered by a device that generates a soft mist for inhalation; it was developed as an alternative to the HandiHaler formulation and is currently approved in more than 75 countries, with initial approval in 2007.

BackgroundTiotropium HandiHaler (tiotropium bromide inhalation powder) is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema. Tiotropium HandiHaler is indicated to reduce exacerbations in patients with COPD 4 (US label only; labels in other countries include clinical data on the effects of tiotropium in reducing exacerbations in the relevant clinical sections 1,2). HandiHaler and Respimat are indicated as a maintenance bronchodilator treatment to relieve symptoms of patients with COPD.1,2General research on COPD medication use has shown that once-daily dosing is correlated with higher adherence compared with twice-daily dosing.5 The Respimat dose of 5 g (two puffs of 2.5 g once daily) was determined to provide comparable pharmacokinetic and pharmacodynamic properties (such as dose to the lung, plasma levels and lung function) to the HandiHaler formulation at 18 g once daily.2While the HandiHaler device comes with a hard capsule containing 22.5 g of tiotropium bromide monohydrate, equivalent to tiotropium 18 g (and a delivered dose of tiotropium 10 g) delivered as an inhalation powder, the Respimat SMI has a unique delivery mechanism that is unlike any other active device currently used in respiratory medicine. It relies on a spring, rather than propellants, to generate a slow-moving cloud from a solution of medication contained in a cartridge, delivering 2.5 g of tiotropium per inhalation (each dose consisting of two inhalations) (equivalent to 3.124 g tiotropium bromide monohydrate) in a volume of 22.1 L per dose. Respimat SMI is a more efficient delivery device, allowing for a reduction of the nominal dose to achieve the best efficacy to safety profile, with a similar dose to the lung.

References SPIRIVA SmPC. Boehringer Ingelheim 2013SPIRIVA Respimat SmPC. Boehringer Ingelheim 2013IMS Health Data, Q2 2012.SPIRIVA Prescribing Information: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021395s008s015lbl.pdfToy EL, et al. Respir Med. 2011;105:435-441.