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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1

What are the main pathologic features in obstructive lung diseases?

- Bronchoconstriction

- Increased airway inflammation

- Increased mucus production

- Airway Remodeling

- Parenchymal lung destruction (emphysema)

2

Describe PS bronchial autonomic innervation

- NT

- Mechanism

- End result

Parasympathetic

- NT: ACh

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

- End result: constricts the airways

3

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

4

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

Anti-inflammatories:

- Inhaled Corticosteroids

- Antileukotrienes

- Cromones

- Theophylline (?)

Bronchodilators

- Short and Long-acting ß-agonists

- Short-acting Anticholinergic ICS/LABA

Combination

Anti IgE

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

5

Overview of Medications for COPD:

- Ant-inflammatories

- Bronchodilators

- Others

Anti-inflammatories:

- Inhaled Corticosteroids

- Roflumilast Bronchodilators

- Short and Long-acting ß-agonists

- Short and Long-acting

Anticholinergics

- Theophylline

6

What method of administration is preferred for bronchodilators?

Inhalation

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

7

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

8

Provide examples of classes of bronchodilators?

- Beta 2 agonists

- Anticholinergics

- Methylxanthines

9

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 (?)

10

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

11

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

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

Short

- Albuterol

- Pirbuterol

Long

- Salmeterol

- Formoterol

- Indacaterol

12

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"

13

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

14

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

15

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

16

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

17

What drug is included in the class of methylxanthines?

Theophylline

18

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

Toxicity:

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

- CNS stimulation: tremors

- Tachyardia

19

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

True

20

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)

21

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

- Liver disease

- CHF

- Older age

- Viral infections

- Febrile illness

- Macrolide antibiotic

- Cimetidine

- Quinolone antibiotics

- Propranolol

- Allopurinol

22

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)

23

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

24

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

25

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

26

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

27

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

28

When should oral corticosteroids be used?

Acute exacerbation of asthma and COPD

- Role in chronic, daily management is limited

- Minimize use!

29

What are some side effects of oral corticosteroids?

(Not uncommon)

- Osteoporosis

- Glaucoma

- Diabetes

- Adrenal suppression

- Skin fragility, bruising

30

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

- LTC4

- LTD4

- LTE4

(- LTB4- more neutrophilic infiltrate?)