Pathophysiology & drugs for chronic airway flow limitation

Question 1

Types of chronic airway flow limitation diseases

Answer 1

asthma
COPD
bronchiectasis
bronchiolitis

Question 2

Sx of chronic obstructive airway diseases

Answer 2

Cough
Sputum
Dyspnea

Question 3

COPD - sites, cells and mediators

Answer 3

central and peripheral airways, lung parenchyma, pulmonary vasculature
neutrophils, macrophages, CD8, CD4, B lymphocytes
LTB4, IL-8, TNFa

Question 4

Asthma - sites, cells, and mediators

Answer 4

central and peripheral airways
eosinophils, CD4 Th2, mast cells, neutrophils, epithelial cells
LTD4, IL-4, IL-5, TNFalpha, many others

Question 5

Bronchiectasis - sites, cells, and mediators

Answer 5

major bronchi, bronchioles
neutrophils
proteases, reactive oxygen, IL-8

Question 6

Bronchiolitis - sites, cells, and mediators

Answer 6

membranous and respiratory bronchioles, immediately adjacent alveoli
neutrophils, eosinophils, macrophages, lymphocytes, mast cells
immunoglobulins, fibronectin, procoagulants

Question 7

Changes in airway resistance in obstructive disease

Answer 7

resistance decreases from central –> peripheral
but in disease, resistance changes in peripheral
considerable changes can occur before symptomatic

Question 8

Subtypes of emphysema

Answer 8

centrilobunar (acinar) - smoking, upper lobe - respiratory bronchioles
Panlobular (acinar) - lower lobe, AAT patients

Question 9

Bronchiectasis etiologies

Answer 9

• Cystic Fibrosis
• Cilial Dysfunction Syndromes
foreign bodies
tracheomalacia
relapsing polychondritis
inhalation of noxious fumes/gases
infective

Question 10

FEV1/FVC for pulmonary disease

Answer 10

< 75% - obstructive

> 90% - restrictive

Question 11

Short-acting beta2 agonists

Answer 11

salbutamol

Question 12

long-acting (~12 hours) beta agonists

Answer 12

salmeterol

Question 13

ultra-long acting beta agonists

Answer 13

indacaterol

Question 14

MOA of beta2 agonists

Answer 14

activation of adenyl cyclase –> increase cAMP –> relaxation of bronchial smooth muscle

Question 15

Combination therapy for b2 agonists

Answer 15

+ inhaled corticosteroids, which upregulates beta 2 receptors
b2 agonists thought to downregulate beta2 receptors

Question 16

Anticholinergic prototype

Answer 16

Long-acting muscarinic antagonist: tiotropium (greater selectivity for M3)

Question 17

MOA of anticholinergics

Answer 17

antagonism at M1, M3 (major) - bronchoconstriction/bronchial secretion

Question 18

PK of anticholinergics

Answer 18

quaternary compound; systemic absorption low
mostly swallowed, but not absorbed
peak effect 30-90 min, duration 6 h

Question 19

SE of anticholinergics

Answer 19

dry mouth
nasal irritation
nosebleeds

Question 20

Leukotriene receptor antagonist prototype

Answer 20

montelukast

Question 21

MOA of LTRAs

Answer 21

antagonist receptors in the lipoxygenase pathway
LT1 receptor = mediate bronchoconstriction / inflammation
leukotrienes = biologically active FAs derived from arachidonic acid
- bronchoconstriction
- hyperactive airways
- inflammation
- mucus hypersecretion

Question 22

SEs of LTRAs

Answer 22

headache, vomiting diarrhea

rare: Churg-Strauss syndrome

Question 23

Methylxanthine prototype

Answer 23

theophylline

Question 24

MOA of methylxanthines

Answer 24

inhibit phosphodiesterase, which breaks down cAMP
adenosine antagonist (contributes more to SE)

Question 25

SE and contraindications of theophylline

Answer 25

narrow margin of safety absorption unpredictable nausea, vomiting, headache, insomnia, tremor, seizures, restlessness, arrhythmias CI: active/symptomatic CAD (increased inotropy, HR)

Question 26

Inhaled corticosteroid prototype

Answer 26

Budesonide, fluticasone

Question 27

MOA of inhaled corticosteroids

Answer 27

``` affects nuclear gene expression anti-inflammatory inhibit expression of pro-inflammatory cytokines and COX-2 immunosuppression catabolic anti-mitotic water retention ```

Question 28

SEs of inhaled corticosteroids

Answer 28

oral candidiasis dysphonia sore throat

Question 29

Monoclonal antibody prototype

Answer 29

omalizumab | sc injection

Question 30

Combination therapy for obstructive airway disease

Answer 30

inhaled corticosteroids + LABA - fluticasone + salmeterol - budesonide + formoterol corticosteroid upregulation of b2 to counteract downregulation by BA

Question 31

Inducer of asthma in a previously non-asthmatic individual

Answer 31

western red cedar sap

Question 32

Mechanism of alveolar breakdown due to smoking

Answer 32

Neutrophil and macrophages recruited to alveolar space, release elastase-containing granules Chemotaxis Inactivating alpha-1-antritrypsin Impairs elastin resynthesis

Question 33

Non-obstructive causes of bronchiectasis

Answer 33

``` CF Kartagener's syndrome (ciliary dysfunction) immune deficiencies necrotizing pneumonias (TB, Staph) ```

Question 34

Obstructive causes of bronchiectasis

Answer 34

foreign bodies neoplasms inspissated mucus congenital abnormalities

Question 35

Complication of emphysema

Answer 35

cor pulmonale