Drugs for Bronchial Asthma and COPD

B2 activation: relaxation

Muscarinic 3 activation: ____

contraction

short-acting B2 agonists

• albuterol (salbutamol)

• levalbuterol

• fenoterol

• terbutaline

long-acting B2 agonists

• arfomoterol

• formoterol

• indacaterol

• olodaterol

• salmeterol

short-acting muscarinic antagonists

• ipratropium bromide

• oxitropium bromide

long-acting muscarinic antagonists

• aclidinium bromide

• glycopyrronium (glycopyrrolate) bromide

• tiotropium

• umeclidinium

• revefenacin

inhaled corticosteroids

• beclomethasone dipropionate

• budesonide

• ciclesonide

• flucticasone furoate (long-acting)

• fluticasone propionate (short-acting)

• mometasone furoate

a biomarker for asthma that provides an indication of the level of inflammation in the lungs.

Fractional concentration of exhaled nitric oxide (FeNO)

name two NO synthase and their defintion

• inducible NOS

  • produced in response to inflammatory cytokines, like:

    • Interferon-alpha

    • Interferon1β

    • tumor necrosis factor alpha (TNF-alpha)

  •  has also been suggested that IL13 upregulates gene expression and transcription in epithelial cells to promote iNOS.

  • iNOS production is a sustained process independent of calcium production.

• constitutive NOS

  • Activation of cNOS occurs in response to a calcium signal introducing basal levels of NO from rapid but short-lived activation and production of NO. 

  • They are corticosteroid-resistant, meaning that basal release of NO is not influenced by steroids.

Interleukin (4, 5, and 13) are released during asthma or type 2 cytokines. Thus, the eyes-nose pathway is important. Why?

Because of the presence of cytokines/Asthma. It will lead to production of iNOS, which will trigger NO and cGMP production and gate-channel opening, leading to relaxation.

name combination therapies for asthma and COPD

• SABA/SAMA

• SABA/ICS

• LABA/ICS

• LABA/LAMA

• LAMA/ICS

• LAMA/LABA/ICS

actions of SABA/SAMA

passive and active

actions of SABA/ICS

active and antiinflam

actions of LABA/ICS

active, long term, and antiinflam

actions of LABA/LAMA and LAMA/ICS

long term

actions of LAMA/LABA/ICS

passive, active, and long term

T/F: Triple therapy (LAMA/LABA/ICS) is utilized for moderate to severe respiratory disease states.

True

normal value for FEV1/FVC1

70% and is 65% for persons who are older than 65

 A value of less than 70% FEV1/FVC1 indicates

airflow limitation and possibility of COPD or asthma.

biologics used for asthma and COPD

• Benralizumab1

• Dupilumab1

• Mepolizumab1

• Reslizumab1

• Omalizumab

• Tezepelumab

T/F: Biologics, including monoclonal antibodies, target specific inflammatory pathways mediated by such entities as Immunoglobulin E (IgE) and the inflammatory cytokines Interlukin-4 (IL-4), IL-5, and IL-13.11 Another pathway that is being challenged involves thymic stromal lymphopoietin (TSLP). 

Each biologic has particular indications, specific dosing, and side effects that need to be monitored. Biologics are mentioned in the GINA 2023 guidelines and research for use of biologics in COPD is promising. It is expected that this strategy will be appearing in the toolbox for treating certain COPD patients, although use of biologics in COPD is not mentioned in GOLD 2023.10 Thus, biologics are highly targeted but costly.

True

T/F: Patients who begin biologic therapy may be able to reduce or eliminate use of systemic and inhaled corticosteroids.

True

Other Medications in the Treatment of Respiratory Disorders

• Leukotriene antagonists

• Antihistamines

• Respiratory stimulants

• Pulmonary surfactants

• Antivirals

• Expectorants

selective B2 agonist that results in prompt, efficacious bronchodilation.

for Asthma, chronic obstructive pulmonary disease (COPD) • drug of choice in acute asthmatic bronchospasm

albuterol

selective B2 agonist that results slow onset, primarily preventive action; potentiates corticosteroid effects

used for Asthma prophylaxis

salmeterol

Nonselective α and β agonist

Bronchodilation plus all other sympathomimetic effects on cardiovascular and other organ systems

Anaphylaxis, asthma, others • rarely used for asthma (β2-selective agents preferred)

Epinephrine

β1 and β2 agonist

Bronchodilation plus powerful cardiovascular effects

Asthma, but β2-selective agents preferred

isoproterenol

inhaled corticosteroids

Alters gene expression

Reduces mediators of inflammation • powerful prophylaxis of exacerbations Asthma • adjunct in COPD • hay fever (nasal)

Fluticasone

systemic corticosteroids

Prednisone

stabilizers of mast and other cells

Alter function of delayed chloride channels • inhibits inflammatory cell activation

Prevents acute bronchospasm

Asthma (other routes used for ocular, nasal, and gastrointestinal allergy

Cromolyn, nedocromil

methylxanthine

Uncertain • phosphodiesterase inhibition • adenosine receptor antagonist

Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm)

Asthma, COPD

theophylline

Block leukotriene D4 receptors

Block airway response to exercise and antigen challenge

Prophylaxis of asthma, especially in children and in aspirin-induced asthma

Montelukast, zafirlukast

Humanized IgE antibody reduces circulating IgE

Reduces frequency of asthma exacerbations

Severe asthma inadequately controlled by above agents

Omalizumab