Development Of Therapeutic Approaches- COPD- Bronchodilation Flashcards
What conditions are considered COPD?
*chronic bronchitis (inflammation)
*chronic obstruction bronchiolitis (obstruction)
*emphysema (alveolar destruction)
What are common symptoms of COPD?
*productive cough
*shortness of breath on exertion
What is chronic bronchitis?
*inflammed bronchi to goblet cells (mucus producing)
*chronic mucus hypersecretion, impaired mucociliary secretion- narrowed airways
*narrowing due to- enlarged glands and inflammatory oedema
What is chronic obstructive bronchiolitis?
*obstruction of smaller airways (bronchioles)
*due to- inflammatory exudate and mucus, inflammatory mediators cause constriction too
*excess mucus due to- increased goblet cells as inflammatory response
*exudate also displaces surfactant layer of bronchioles- affects surface tension- airways close easier but open harder
What is emphysema?
*lung tissue destroyed- reduced elastic recoil force to drive air out of lungs- decreased expiratory flow
*destruction of airways = enlargement of alveoli
*loss of alveolar walls rich in capillaries means dead spaces crested
What are the COPD GOLD guidelines?
Global initiative for chronic Obstructive Lung Disease
Gold 1- mild- FEV1 >80%
Gold 2- moderate - FEV1 between 50-80% predicted
Gold 3- severe- FEV1 between 30-50% predicted
Gold 4- very severe- FEV1 <30% predicted
What is the general management of COPD?
*bronchodilator therapy
*non pharmacological- smoking cessation
*support - diet, exercise, vaccines
*pulmonary rehab- long term oxygen, lung surgery?
What is the key to impeding disease progression?
*early diagnosis
*therapeutic intervention
*indemnification of therapeutic targets
Give an example of how molecular biology has been used to identify subtypes of receptors and improve drug design.
Development of improved bronchodilators for COPD has allowed three subtypes of receptors to be cloned and expressed- M1, M2, M3
*M1 block- reduced bronchoconstriction
*M2 block- increase ACh DONT WANT
*M3 block- reduced bronchoconstriction
Need M1 and M3 selectivity
What miscarinic antagonist is m1 and m3 selective?
Tiotropium bromide (spiriva) long acting bronchodilator
Dissociates rapidly from M2 receptors but slowly from m1&m3
What was the thought process behind the discovery of aclidinium bromide?
Discover potent novel M3 antagonist with less reduced ACh systemic side effects eg dry mouth with spiriva
Aclidinium had longer duration than tiotropium bromide
Rapid plasma hydrolysis- low potential for systemic side effects
What is the aclidinium bromide inhaler called?
Eklira genuair
Second generation muscarinic antagonist
What is triple therapy in COPD?
ICS + LABA + LAMA
Limitation- ICS increased risk of pneumonia
What block buster drugs were invented?
Combination therapy- seretide (LABA + ICS)
Revlar
