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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This note was uploaded on 12/03/2011 for the course MEDICINE 350 taught by Professor Dr.aslam during the Winter '07 term at Medical College.

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

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