Respiratory pharmacology

Question 1

Asthma

Answer 1

A reversible obstructive lung disease, characterized by bronchoconstriction due to hyperresponsiveness of the airways to physical, chemical and pharmacological stimuli

It is a chronic inflammatatory condition with acute exacerbations

Asthma can be life threatening if not propertly managed

Question 2

COPD

Answer 2

An obstructive lung disease that overtime makes it hard to breathe

Involves inflammation and thickening of the airways

It also involves destruction of the tissue of the lung where O2 is exchanged
Sometimes referred to as either chronic bronchitis or emphysema

3rd leading cause of death in US

Question 3

Allergic response of asthma

Answer 3

Ag triggeres peripheral lymphoid tissue to release IgE, a sensitized mast cell and the IgE interact, leading to release of :
-histamine, tryptase, LTC4, D4, PGD2

Acute response: in minutes, degranulation-> histamine, leukotrienes, cytokines, proteases–> bronchoconstriction (immediate early reaction)–> mediators-> trigger mediators

In hours-> secretion –> cytokines and chemokines–> late phase reactions and inflammation

Question 4

Treatment groups of asthma

Answer 4

Quick relievers: meds to quickly reverse the symptoms of asthma (short acting bronchodilators-albuterol)

Exacerbation of Asthma: short causes of oral steroids (antii inflammatory- prednisone)

Long-term controllers: include meds to prevent airway narrowing over time, inhaled corticosteroids (fluticasone), Long acting bronchodilators (LABAs- never used alone, salmetorol), and Leukotriene modifiers (montelukasts

Question 5

Airway narrowing

Answer 5

causes the symptoms of asthma, due to smooth muscle hypertrophy and constriction, mucous gland hypertrophy and hypersecretion
Vascular engorgement and leakage causing airway wall edema, and subepithelial basement membrane thickening and fibrosis

Question 6

Omalizumab

Answer 6

Anti- IgE receptor therapy
Ige and allergen activates high affininty receptors (FCErI) in mast cells and and low ffinity receptors (FceR2, CD23) on other inflammatory cells

OMALIZUMAB binds free iGE, prevents mast cell degranulation and the resulting inflammation

Therapeutic use: pts with severe asthma who remain poorly controlled despite high doses of inhaled steroids combined with long-acting bronchodilators

Question 7

Bronchodilator drugs

Answer 7

3 main classes
SABA (short acting beta agonists)- albutorol, immediate reversal of airway obstruction
SandLABAS: salmetorol, formoterol- prevent bronchoconstriction, LABA- never used alone in asthma

RELAX constricted airway smooth muscle

Question 8

Albuterol and Salmetorol/formoterol

Answer 8

Albuterol (SABA), bronchodilator
Salmetorol and Formoterol (LABA): bronchodilator treatment of choice in asthma, have minical side effects when used correctly
LABA-neverused alone in asthma

SABA- 3-6 hours
LABA- >12 hours

Directly stimulate B2 receptors in airway smooth muscle
Rapid bronchodilator action is attributable to a direct effect on airway smooth muscle

Question 9

SE of B2 selective agonists

Answer 9

dose related, CV disease, administer by inhalation to avoid other rists

Has tolerance (desensitization, subsensitivity)- down regulation of the receptor

AS more and more saba is used you need more
LABA is never used alone

Question 10

Theophylline

Answer 10

Methylxanthines, non selective phosphodiesterase (PDE) inhibitor and adenosine receptor antagonism,

SE: headache, tachycardia, cardiac arrhythmias and seizures

Question 11

Steroids

Answer 11

Oral corticosteroids (prednisone) for a short period of time, 3 to 10 days is the only treatment for asthma axacerbations

ICS are considered as first line therapy in Moderate to severe asthma (not mild)

Question 12

MOA of Corticosteroids in asthma

Answer 12

iinflammatory stimuli (IL1 TNF a) acticivates NFkB–> histone acetyltransferase (HAT)–> acetylation of core histones, increased expression of genes encoding multiple inflammatory proteins

Cytosolic glucocorticoid receptors bind corticosteroids – inhibit HAT activity, reverses histone acetylation–> suppression of activated inflammatory genes

Steroids dont directly affect contractile response of airway, inhibit late response and hyper responsiveness

Question 13

Steroid effect on B2 adrenergic responsiveness

Answer 13

steroids increase transcription of B2 receptor (prevent down regulation)
B2 agonists enhance glucocorticoid recepotr

B2 agonists and corticosteroids enhance eachothers beneficial effects in asthma therapy

Question 14

Chronic use of LABA

Answer 14

should not be done in monotherapy, could make things worse

Question 15

Systemic/oral steroids

Answer 15

Prednisone most common, takes a few days to kick in
short courses are indicated for exacerbations of asthma

Be careful when taking off after long term use

Question 16

Clinical use inhaled corticosteroids

Answer 16

1st line therapy for all pts w/ persistent astham, started in any pt who needs to use a B2 agonists inhaler more than 2x weekly, effectivel in mild, moderate and severe asthma in kids and adults

Question 17

Leukotriene modifiers

Answer 17

Montelukast, indicated as an add on therapy

Question 18

Aspirin induced asthma

Answer 18

aspirin hypersensitivity,

Question 19

Anti interleukin 5 therapy

Answer 19

IL5 is a pro eosinophilic cytokine mediator of eosinophilic hematopoiesis and contributes to eosinophilic inflammation in the airways, Mepolizumab

> 150 ul of eosinophil is indicated

Question 20

COPD and treatment

Answer 20

Progressive small airway narrowing and fibrosis (chronic obstructive bronchiolitis)
Destruction of the alveolar walls (emphysema)

Pharmacological treatment of stable COPD:
Short acting bronchodilators: Beta2 agonists (abuterol), Anticholinergics (ipratropium), combination therapy

Long acting bronchodilators: Beta 2 agonists (salmetorol, formoterol) can be used as monotherapy unlike asthma, anticholinergics (tiotropium), combination therapy

Inhaled steroids (fluticasone, budesonide), Bronchodilators + ICS

Question 21

Anticholinergics

Answer 21

Ipratropium bromide- short acting
Tiotrpium- long acting

RElaxes airway smooth muscle, decreases mucus secretion, Ach released onto the airway smooth muscle causes bronchoconstriction via M3 muscarinic receptors and mucus secretion via the M1 and M3 muscarinic receptors

Adverse effects and contraindications are of less concern with anticholinergics administered by inhalation

Effect is greates in affected airways

Question 22

Corticosteroids in COPD

Answer 22

dont work well

Question 23

Cystic fibrosis

Answer 23

AR disorder caused by mutation of chloride channel, prduction of abnormal mucus which depresses lung function

Question 24

Treatments

Answer 24

CF has no cure, Ab to treat lung infections, anti inflammatory, inhaled bronchodilation, rhDNAase, ivacaftor

Question 25

Dornase alpha inhaled

Answer 25

infiltrating PMNs release DNA which has a high viscosisty

DNAse breases in up , allows for sputus clearance, imporoves lung function, decreases frequency of infection

Question 26

Ifacaftor

Answer 26

binds to defective protein at the cell surface, opens up the chloride channel and restores the proper flow of fluids and sodium

Luma-ivacaftor- caution in pts with advanced liver disease

Question 27

F508del mutation

Answer 27

improper folding of CFTR protein during synthesis, most common mutation–> Cf (50 % are homozygous, 40 % heterozygous)

Class 2 mutation when the protein doesnt make it to the cell surface