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Emerging Therapies - COPD

Emerging Therapies - COPD - Emerging Therapies for COPD DM...

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Unformatted text preview: Emerging Therapies for COPD DM Seminar 17 Feb 06 AS Paul Introduction • No present treatment reverses COPD • Rational treatment • Underlying cellular and molecular mechanisms • Chronic inflammation • Neutrophils, macrophages, CD 8 lymphocytes • F i b r o s i s • Destruction (neutrophil elastase, MMP) • Asthma is different. Newer interventions • Smoking cessation • New drugs – Bronchodilators – Mediator antagonists – Anti-inflammatory agents – Protease inhibitors – Remodelling agents – Drug delivery systems • Bronchoscopic LVRS Difficulties • Molecular & cell biology still not understood • Animal models lacking for early drug testing • Long term studies (> 3 yrs), large no of pts. • Surrogate markers- short term monitoring Smoking Cessation • Major cause for COPD • Nicotine addiction • Q u i t r a t e s – Placebo 6% – NRT and behavioural therapy 9% – Bupropion (6-9 wks) 18% at 1 yr – ?? Nortryptilline • Well tolerated, sleeplessness, epilepsy • Better drugs may emerge. New Bronchodilators • Mainstay; need improvement • LABA once daily ?? • Tiotropium recently introduced • Slow diss from M1,M3 receptors • Better than ipratropium QID • Symptom control, QOL • Decrease in exacerbations • Additive effects with LABA • Bronchodilator of choice in COPD MEDIATOR ANTAGONISTS • On going inflammation; even in ex- smokers • Neutrophillic inflammation • Reactive oxygen species • Inhib of Leukotriene B4,chemokines, TNF,iNOS, anti-oxidants. Leukotriene B4 • Potent chemoattractant of neutrophils • Increased in sputum of COPD pts • Synergy with IL-8 • BLT1(granulocyte monocyte) • BLT2 (T lymphocytes) • Antagonists eg LY29311 etc • 5’ lipoxygenase inhibitors eg zileuton(synthesis) Chemokine inhibitors • IL-8 marked increase, disease severity • Monoclonal Ab to IL-8 in clinical trials • Block common receptor for CXC family • CXCR1, CXCR2 • Monocyte chemotactic protein 1:CCR2 TNF alpha inhibitors...
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Emerging Therapies - COPD - Emerging Therapies for COPD DM...

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