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Define emphysema

COPD w/ permanently enlarged air sacs distal to terminal bronchioles w/ destruction of their walls and w/o obvious fibrosis

1

What is the main enzyme implicated in emphysema?

Neutrophilic Elastase

2

5 morphological subtypes of emphysema

1. centrilobular - esp. w/ cigarettes
2. panlobular / panacinar - a1-antitrypsin and end-stage centrilobular
3. paraseptal - assoc. w/ pulmonary fibrosis. may -> spontaneous pneumothorax
4. irregular - associated w/ pulmonary scars
5. interstitial - subcutaneous. due to trauma or elevated intraalveolar pressure

3

What type of emphysema is cigarette smoking usually associated with?

Centrilobular
Anthracosis often present

4

What part of respiratory tree is involved in centrilobular emphysema?

Primarily respiratory bronchioles due to high conc. of inhaled irritants
More prominant in upper lung fields

5

Chronic Bronchitis Definition

Productive cough w/o discernible cause for at least 3 months in 2 consecutive years

6

Reid index

Ratio of thickness of mucous glands to total thickness of airway wall.

Elevated in chronic bronchitis

7

status asthmaticus

most severe subtype of asthma - prolonged interval of continual symptoms, unresponsive to treatment

May be life-threatening

8

Common effector pathway of asthma

Stimulus in susceptible host -> release of inflammatory mediators -> increased vascular permeability, edema, neural and cytokine mediated bronchoconstriction, mucus hypersecretion, chemotaxis of additional inflamm. cells -> amplification

9

Major chemical mediators of acute phase of asthma

Histamine
LTC4, D4, E4
PGD2 - mucus prod
PAF
Parasympathetic neural reflexes

10

What happens in late phase of asthma?

Infiltration of white cells (esp. eosinophils) in response to locally released chemotactic factors
LTB4, eotactin
Prolongation and augmentation of disease process

11

2 common drugs that can contribute to asthma

aspirin: decreased prostaglandin production and relative increase in leukotriene

B-antagonists: may precipitate bronchospasm

12

What respiratory disease is assoc. w/ mucus plugs?

asthma

13

Curschmann Spirals and Charcot-Leyden Crystals - what are they and what are they associated with?

Curschmann Spirals: mucoid swirls of epithelial cells
Charcot-Leyden Crystals: extruded eosinophil granules - needle-like crystals

14

What is bronchiectasis

Permanent airway dilation due to recurrent infections w/ necrosis

15

Atelactasis neonatorum

Incomplete expansion of lungs at birth

16

What happens to the mediastinum in obstructive atelactasis?

Mediastinal shift toward atelactic lung

17

What happens to the mediastinum in compression atelactasis?

Mediastinal shift away from atelactic lung

18

Effects of alpha, B1, and B2 agonists

alpha: vasoconstriction and vasopressor -> decongestion
B1: increased myocardial conductivity, increased HR and contractile force
B2: relax bronchial sm. muscle, inhibit inflamm. mediator release, stimulate mucocilliary clearance

19

What receptors do epinepherine, ephederine, and isoproterenol work at?

epinepherine: B1, B2, alpha
ephedrine: B1, B2, alpha
isoproterenol: B1, B2

20

How do selective B2 agonists work?

increase AC -> increased cAMP -> sm. muscle relaxation

21

3 short acting B2 agonists

Albuterol
Levalbuterol
Pirbuterol

22

What is the difference between albuterol and levalbuterol?

Albuterol is a racemix mix of R and S enantiomers
Levalbuterol is only R (active)
considered equal, but levalbuterol is expensive.

23

What is the difference between salmeterol and formoterol?

Both last 12+ hrs
Formoterol is a full B2 agonist and has faster onset
Salmeterol is a partial B2 agonist

24

2 long acting B2 agonists available in 1x daily dosing?

Indacaterol
Vilanterol

Both available as DPI

25

What genetic factor has been associated with increased susceptibility to B2 agonist tolerance?

Gly16 polymorphism of B2 receptor.
-> reduced responsiveness to agonists

26

What is the recommendation regarding use of long acting B2 agonists in treating asthma?

Black box warning: should not be used as monotherapy. increased risk of death

27

What is the primary mechanism of action of anticholinergics in treatment of obstructive respiratory disease?

Reduction of intrinsic vagal tone

28

In what patient population is ipratropium contraindicated?

Those w/ soy lecithin or peanut allergy.
Propellant contains lecithin

29

2 long acting anticholinergic drugs for control of COPD and sites of action.

Tiotropium blocks M1-M3 receptors, but dissociates from M2 quickly. M1 and 3: long duration of action
Aclidinium blocks M1-M5. pharmacological action at M3