Drugs for asthma Flashcards
What happens to the airway of an asthmatic patient? (3)
Tightened muscles constrict airway
Mucus filles channel
Inflamed/thickened airway wall
What causes the mucosal inflammation seen in asthma patients?
activated eosinophils, mast cells and T lymphocytes within the context of a remodelled airway with mucous metaplasia
An increase in smooth muscle
fibrosis and angiogenesis
What is the hallmark of COPD?
Airflow limitation
How does COPD differ from asthma? (4)
Different in terms of etiology, cellular mediators, treatment, and prognosis
Describe Forced Vital capacity
Determination of vital capacity from a maximally forced effort
Define expiratory volume (FEV1)
Volume that has been exhaled at the end of the end of the first second of forced expiration
What do asthma and COPD patients have in common regarding their respiration?
Decreased FEV relative to their FVC
What does Omalizumab block?
IgE
What does Mepolizumab and Reslizumab inhibit?
Interleuken 5
How are inflammatory mediators released by mast cells?
Immunological stimuli activate IgE receptors
What are the three therapeutic benefits of asthma/COPD and what are two* examples of each?
Decreased inflammation
- Glucocorticoids
- Antileukotrienes
Bronchodilation
- beta2 adrenergic receptor agonists
- Muscarinic receptor antagonists
Decreased inflammation and bronchodilation
- methylxanthines
How do glucocorticoids decrease inflammation?
Suppression of gene expression
How to antileukotrienes decrease inflammation?
Decrease of leukotriene synthesis
OR
antagonization of CysLTR
How do beta adrenergic receptor agonists dilate brochi?
Increasing cAMP
How do muscarinic receptor antagonists dilate broncholes?
By blocking activation of muscarinic receptors by endogenous acetylcholine
How do methylxanthines decrease inflammation and dilate broncholes?
By inhibiting adenosine receptor and increasing cAMP
Name a clucocorticoid
Budesonide
What are all the effects of glucocorticoids?
local and systemic inhibition of inflammatory mediator synthesis, and phagocytosis
What are the antiinflammatory actions of glucocorticoids?
Decreased production of prostaglandins, cytokines and interleukins
Decreased proliferation and migration of lymphocytes/macrophages
What cells are decreased after the actions of glucocorticoids?
Airway immune mediators: eosinophils, Th2 lymphocytes, mast cells, macrophages, and dendritic cells
Also redutions in epithelial cell inflammation, endothelial cell permeability, and hyperreactivity of bronchiolar smooth muscle
True/False? Corticosteroid therapy is of significant benefit to both asthma and COPD patients
True/False? Corticosteroid therapy is of significant benefit to both asthma and COPD patients
minimal benefit for COPD patients
What is the mechanism of action of glucocorticoids?
They bind to the glucocorticoid receptors, activate histone deacetylase 2 (HDAC2) and inhibit histone acetyltransferases (HAT)
How are (most) leukotrienes named?
Montelukast
zafirlukast
——lukast
How to leukotrienes work?
Competitive antagonists of CysLTR1
Are antileukotrienes work better to treat acute episdes of bronchoconstriction, or rather as a prophylactic?
Prophylactic
Which autonomic nervous system causes bronchodilation?
Sympathetic
How do beta adrenergic receptor agonists work?
Beta adrenergic receptors are found all over bronchial smooth muscle
Activation of Beta2 receptors leads to smooth muscle relaxation and therefore bronchodilation
Agonists sensetize these receptors
How does Ma Huang (ephedrine) work to treat asthma?
Nonselectie adrenergic agonist
What is the medication of choice for all types of asthma?
Salbutamol (albuterol)
How does Salbutamol work?
Short acting beta2 receptor agonist
Rapid onset of action (15 mins)
Is salbutamol better prophylactically or acutely?
acute
True/False? Albuterol is a racemix mixture, but R-albuterol is more effective
True/False? Albuterol is a racemix mixture, but R-albuterol is more effective
Name a methylxanthine
Theophylline
Caffeine
How do methylxanthines work?
Phosphodiesterase inhibitor, leading to increased intracellular cAMP
What are negative effects of Theyphylline?
Decreased number/activity of immune mediators,
What is the principal autonomic influence in the normal regulation of bronchomotor tone?
Parasympathetic NS tone
What is cholinergic control of airway smooth muscle dominated by?
Muscarinic receptor M3 subtype (but all are present)
What is the bronchodilator of choice for the treatment of COPD?
Inhaled muscarinic receptor antagonists
What drugs are used to prevent acute episodes of Asthma and COPD?
Inhaled glucocorticoids (in more serious cases, LABAs)
What drug is used to treat an acute episode?
SABAs
What are advantages of routine first-line therapies for asthma and COPD delivered by inhalation?
Convey drug directly to the site of patholoty
Much lower doses
Reduces side effects
What is the typical treatment for asthma?
Multiple drugs with continuous evaluation and adjustment depending on patient responses
What should adults with mild/intermittent asthma take?
Infrequent use of fast acting “rescue” bronchodilator (SABAs)
What are signs of increasing asthma severity
Nocturnal symptoms, daytime symptoms more than twice a week, limited normal activity
What is a risk of LABA monotherapy? How is this countered?
Death (yikes) take in combination with inhaled corticosteroids
What happens if the medication doesn’t help?
Larger dose
What should you take for severe asthma?
Oral corticosteroids
Stopping inhaled corticosteroid therapy altogether (is/is not) recommended for adults
Stopping inhaled corticosteroid therapy altogether (is/is not) recommended for adults due to increased risk of exacerbated
What drugs treat COPD?
Salmeterol or Formoterol (LABAs)
