9/22- Pharmacology of Obstructive Lung Diseases Flashcards Preview

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Flashcards in 9/22- Pharmacology of Obstructive Lung Diseases Deck (46)
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What are the main pathologic features in obstructive lung diseases?

- Bronchoconstriction

- Increased airway inflammation

- Increased mucus production

- Airway Remodeling

- Parenchymal lung destruction (emphysema)


Describe PS bronchial autonomic innervation

- NT

- Mechanism

- End result


- NT: ACh

- Binds muscarinic M3 receptors (cholinergic) on sm cells within bronchial walls

- End result: constricts the airways


Describe sympathetic bronchial autonomic innervation

- NT

- Mechanism

- End result

- NT: catecholamines

- Binds adrenergic receptors

- Airway sm cells express B2 adrenergic receps mainly (expressed elsewhere too, but mostly on smooth muscles)

- End result: bronchodilation


Overview of Medications for Asthma - Ant-inflammatories - Bronchodilators - Others


- Inhaled Corticosteroids

- Antileukotrienes

- Cromones

- Theophylline (?)


- Short and Long-acting ß-agonists

- Short-acting Anticholinergic ICS/LABA


Anti IgE

(Thus, you can see that bronchodilation may be achieved by promoting sympathetic stimulation or blocking PS)


Overview of Medications for COPD:

- Ant-inflammatories

- Bronchodilators

- Others


- Inhaled Corticosteroids

- Roflumilast Bronchodilators

- Short and Long-acting ß-agonists

- Short and Long-acting


- Theophylline


What method of administration is preferred for bronchodilators?


- Can be given systemically if really severe/can't inhale


What is the benefit of combining bronchodilators in COPD?

- May improve efficacy

- May decrease the risk of side effects compared with increasing the dose of a single bronchodilator


Provide examples of classes of bronchodilators?

- Beta 2 agonists

- Anticholinergics

- Methylxanthines


How do the following effect bronchodilation?

- Beta agonists

- Muscarinic antagonists

- Theophylline

- Beta agonists: activation of AC -> more cAMP -> bronchodilation

- Muscarinic antagonists: block ACh activation of bronchoconstriction

- Theophylline: blocks PDE, increasing cAMP levels (by preventing cAMP -> AMP degradation) and blocks adenosine (?)


In addition to relaxing airway sm, what other functions to B2 agonists have?

- Inhibition of plasma exudation and airway edema

- No effect on chronic inflammation

- Don't want too use to frequently (bad outcomes), so used to supplement long-acting treatment


Provide example drugs for short and long-acting B2 agonists?

(Don't need to remember drug names at this point)


- Albuterol

- Pirbuterol


- Salmeterol

- Formoterol

- Indacaterol


Describe short-acting beta agonists

- Onset

- Duration

- Frequency

(Albuterol is the most commonly used rescue inhaler)

- Onset: rapid, within 10-15 min

- Duration: max 4-6 hrs

- Most effective when used on "as-needed" basis, or "rescue"


Describe long-acting beta agonists

- Duration

- Frequency

- Effects

(Salmeterol and formoterol)

- Similar to short-acting, but longer duration: 12 hrs

- Dosed 2x/day

- Variable effects on exercise, exacerbation, QOL

- Should only be used as add-on to ICS (immunocorticosteroids?) in asthma


Recommendations on use of LABAs in Asthma?

Not recommended as monotherapy for long-term control

- Consider as adjunctive therapy in patients aged >5 years who require more than a low-dose ICS

- Consider adding an LTRA in patients aged >5 years

Not recommended for treatment of acute symptoms

May be used before exercise to prevent EIB


How to anticholinergics function to alleviate asthma and COPD (mechanism/targeted pathology)?

- Block vagal pathways-decreases vagal tone

- Blocks reflex bronchoconstriction caused by inhaled irritants

- Role in asthma is less clear (than in COPD) may have added benefit in combination with beta2-agonists in acute asthma

- Delivered locally, but may be associated with systemic effects (since cholinergic): most common = dry mouth


Provide examples of short and long acting anticholinergics (don't memorize names)?

- Ipratropium: slow onset (30 min)

- Tiotropium: bronchodilation, long acting (24 hrs)

Overall, slower than B2 agonists, which is why the latter are preferred in rescue situations


What drug is included in the class of methylxanthines?



Describe Theophylline

- Functions

- Mechanism

- Duration

- Dosing

- Metabolism

- Toxicity

- Bronchodilator (mild-moderate) with questionable anti-inflammatory properties

- Mechanism uncertain (probably PDE inhibition)

- Long acting dosage form

- Very narrow therapeutic window (get ASEs easily!)

- Recommended serum concentration = 5-8 ug/mL; dose varies person to preson

- Metabolism: liver


- GI (most common): irritation, burning, nausea

- CNS stimulation: tremors

- Tachyardia


T/F: Theophylline has numerous drug-drug/disease-drug interactions?



What drugs/diseases may increase metabolism of Theophylline (decrease levels)?

- Cigarette smoking

- Young age

- Hyperthyroidism

- Barbiturates

- Phenytoin (ex: if someone stops smoking, may have super high theophylline levels)


What drugs/diseases may decrease metabolism of Theophylline (increase levels)?

- Liver disease


- Older age

- Viral infections

- Febrile illness

- Macrolide antibiotic

- Cimetidine

- Quinolone antibiotics

- Propranolol

- Allopurinol


What are classes of anti-inflammatory agents used in asthma/COPD treatment?

- Inhaled Corticosteroids

- Leukotriene Modifiers

- Mast-cell stabilizers (Cromones)

- Anti Ig-E therapy (severe allergic asthma)


Describe inhaled corticosteroids

- Systemic effect

- Effects of chronic use

- Frequency

- Not used in what situations

- When to use in asthma

- When to use in COPD

- Potent local anti-inflammatory with minimal systemic toxicity

- Chronic use decreases airway hyper-responsiveness

- A "preventer", not a "reliever"

- Daily regularly scheduled - Generally not used in acute exacerbations

- Asthma: 1st line in daily asthma management!

- COPD: Reserved for more moderate-severe disease with frequent exacerbation


What are the cellular effects of corticosteroids?

Inflammatory cell effect

- Decrease numbers of eosinphils (apoptosis), mast cells, and dendritic cells

- Decrease cytokine release by T lymphocytes and macrophages

Structural cell effect

- Decrease cytokines/mediators of ep cells

- Decrease endo cell leak

- Decrease B2 receps and cytokines in airway SM

- Decrease mucus secretion


What are the beneficial effects of inhaled corticosteroids that make them the first-line therapy for persistent asthma?

(1st line therapy even in mild persistent disease)

- Reduce asthma symptom severity

- Improve quality of life

- Improve pulmonary function

- Reduce rescue inhaler use

- Reduce exacerbations/ hospitalizations/ ?mortality

- Reduce bronchial hyperreactivity

- Slow deterioration of lung function

- ? May prevent airway remodeling

Basically: improve lung function and symptoms and health status, decrease exacerbations; decrease mortality

- Significant anti-inflammatory effects


What are some safety/risk considerations of inhaled corticosteroids?

- Small risk for topical adverse events at recommended dosage

- New formulations have lower systemic bioavailability and higher topical potency

Reduce potential for adverse events by:

- Using spacer and rinsing mouth

- Using lowest dose possible

- Using in combination with long-acting beta2-agonists


What are the beneficial effects of inhaled corticosteroids that make them somewhat effective in COPD? Negatives?

- Modest effect on long-term deterioration in lung function (limited because COPD involves neutrophilic inflammation)

- Significant decrease in exacerbations

- Improvement in quality of life

- Modest effect on mortality

- Recommended by guidelines for severe disease and in patients with recurrent exacerbations

BUT: Increase risk of pneumonia


When should oral corticosteroids be used?

Acute exacerbation of asthma and COPD

- Role in chronic, daily management is limited

- Minimize use!


What are some side effects of oral corticosteroids?

(Not uncommon)

- Osteoporosis

- Glaucoma

- Diabetes

- Adrenal suppression

- Skin fragility, bruising


What are the most active leukotrienes in asthma (and COPD?) treatment?

- LTC4

- LTD4

- LTE4

(- LTB4- more neutrophilic infiltrate?)