Lower Respiratory Pharmacology Dr. Roane Flashcards
(48 cards)
What are the two most common conditions associated with the Lower Respiratory diseases?
Obstructive:
Asthma and COPD
What are Obstructive and Restrictive conditions referred to?
Obstructive means reduced FEV1 (forced expiratory volume of 1 second)
Restrictive means reduced Vital Capacity (all the volume that can be breathed in
FVC (forced vital capacity): maximum that can be breathed in -> maximum that can breathed out (residual volume will stay)
How much air should be exhaled in a normal FEV1?
70-80%
slightly less with >65 of age
What is the function of the smooth muscles wrapped around the bronchiole?
they regulate how much air can be moved (Bronchodilation, Bronchoconstriction)
with increased force, there is lower surface pressure
What is Asthma?
-disease of diffuse airway inflammation, extra excreted mucus, bronchoconstriction
-caused by a variety of triggering stimuli
-resulting in partially or completely reversible bronchoconstriction
Symptoms of Asthma
-Dyspnea (difficulty breathing)
-chest tightness
-cough
-wheezing
-possible anxiety
Treatment of Asthma
-inhaled beta-2 agonists (short-term)
-muscarinic blockers
-inhaled corticosteroids (long-term treatment)
Epidemiology
-Asthma is more common in African American and Puerto Ricans
-some genetics suspected to be involved
ORMDL3 and many genes coding for cytokines
How do allergens involved in asthma attacks affect the airways?
Allergens -> cause Inflammatory mediator secretion
-bronchoconstriction (muscarinic effect)
-vasodilation
-mucus hypersecretion
-plasma exudation, edema
-activation of sensory nerves
Consequences of chronic inflammation of the airways due to asthma?
-structural changes
-subepithelial fibrosis (the membrane will be less elastic)
-smooth muscle hypotrophy (bigger) and hyperplasia (more cells)
What happens in an asthma attack?
-Bronchoconstriction: smooth muscle contraction + Tissue inflammation
-Mucus secretion/edema
-Mismatch between ventilation and pulmonary blood flow
What happens when the ventilation and perfusion don’t match?
-Normally, pulmonary blood flow goes to highly ventilated regions
-in asthma, constricted airflow cause a mismatch in ventilation and perfusion (passage of blood) -> dysfunction in gas exchange
If the airways are blocked what happens to pO2 and pCO2?
pO2 goes down
pCO2 goes up
What is the status asthmaticus?
-Non-reversible asthma attack
-can be fatal
COPD
-persistent airflow limitation from the consequences of chronic inflammation from smoking (can also affect people with air pollution)
Subtypes of COPD
-chronic bronchitis
-Emphesyma (damage of lung tissue - air sacs)
-small airway disease: small bronchioles are narrowed and reduced in number
Drugs that are used in COPD and asthma
-Bronchodilators
>Beta-2 adrenergic receptor agonists
>Anticholinergics (Muscarinic antagonists)
>Methylxanthines
-Corticosteroids
-Leukotriene modifiers
-Mast cell stabilizers
-Immunomodulators
What are the ß-agonists used for Asthma/COPD?
-SABA (short-acting): Albuterol, Terbutaline, levalbuterol (Xopenex), metaproterenol (Alupent),
and pirbuterol (Maxair)
-LABA (long-acting): Salmeterol, Formoterol, Vilanterol and Olodaterol
Adverse effects ß2 Agonists
due to partial ß1 activity
-cardiac arrhythmia (faster heart rate)
-decrease in plasma K+
-reduce insulin secretion -> increase in blood glucose
Which drug class is associated with increased mortality in patients having asthma?
LABA (Long-acting ß agonists)
-Salmeterol, Formoterol, Vilanterol and Olodaterol
-indicated for COPD - not asthma
Which enzymes regulate the contraction and relaxation of smooth muscles in the airway?
-Myosin light chain kinase: phosphorylates the myosin light chain -> interact with actin-fiber-> CONTRACTION
-Myosin light-chain phosphatase removes Phosphate from the myosin light chain -> RELAXATION
(Relaxation can also occur when Ca entry is stopped)
MOA for ß2-Agonists
-binds to ß2-receptor
-activates adenylate cyclase -> producing cAMP
-cAMP turns on protein kinase A (PKA)
-PKA inhibits MLCK -> RELAXATION of smooth muscles -> BRONCHODILATION
Why are some ß-agonists short-acting?
Because cyclic AMP (activating PKA -> PKA inhibiting MLCK -> RELAXATION) has a short halflife
-cAMP gets metabolized by Phosphodiesterase (PDE)
What is the final effect of Phosphodiester inhibitors (PDE-inhibitor)?
PDE4 metabolizes cAMP to AMP
-cAMP is needed to activate PKA -> PKA deactivates MLCK causing BRONCHODILATION
-PDE inhibitor inhibits PDE4 so there is more cAMP to activate PKA
-relaxes smooth muscles
-inhibit inflammatory cells
