Respiratory Week 1 Review

BA-pMDI

an aerosol inhaler that is activated by inspiration

pMDI

an aerosol inhaler that uses coordinated administration

DPI

a breath activated inhaler that uses a powder inhalation

SMI

inhaler that creates a slow, fine aerosol (Respimat)

percentage of patients using inhalers with administration errors

50%

MDI administration

shake before administration

slow, prolonged breath timed with actuation

hold breath for 10 seconds

DPI administration

do NOT shake before administration

quick, steady breath

hold for 10 seconds

(rinse mouth for ICS)

SMI BUD

60 days from canister assembly

Asthma

chronic inflammatory disorder of the airways

atopic asthma

allergic asthma

nonatopic asthma

nonallergic asthma

mixed asthma

allergic and nonallergic asthma

types of asthma

exercise-induced

occupational

cough variant

glucocotricosteroid-resistant

typical asthma symptoms

wheezing, SOB, cough, chest tightness

asthma steps

1. activation of mast cells

2. infiltration of eosinophils

3. increased activated helper T 2 cells

asthma risk factors

airway hyperreactivity

allergen exposure

atopy

early menarche

familial history of asthma

male gender

tobacco exposure

obesity

asthma presentation

narrowing of airways

hyperresponsiveness of airways

increased bronchial response to stimuli

th2 cells

responsible for cytokine production that drive eosinophil attack

Asthma allergen triggers

dust mites

pollens

molds

pet dander

cockroach droppings

asthma irritant triggers

cigarette smoke

strong fumes

woodfires/charcoal grills

NSAID induced asthma

asthma caused by inhibition of the COX pathway that pushes arachindonic acid to make leukotrienes (asthma bois) instead of COX

Drugs used for NSAID induced asthma

LT inhibitors, lipooxygenase inhibitor (zileuton)

Bronchodilator classes

Beta-2 agonists, muscarinic antagonists, methylxanthenes

Beta-2 agonist MOA

1. activate beta-2 receptor -> activate adenyl cyclase and increase cAMP -> smooth muscle relaxation

2. prevent mediator release from mast cells

SABAs

albuterol*, levabuterol*, metaproterenol, pirbuterol, terbutaline

LABAs

Formoterol, Salmeterol

Ultra LABAs

Olodaterol*, Indacaterol, Vilanterol*

Methylxanthine MOA

non-selective PDE inhibitor

PDE4 inhibitor

Roflumilast

Roflumilast MOA

inhibits breakdown of cAMP by PDE4

SAMA

Ipratropium

LAMA

tiotropium, aclidinium, umeclidinium

anticholinergics MOA

competitively bind M3 receptors to block ACh binding

antimuscarinic AEs

anti-SLUD (salivation, lacrimation, urination, defecation)

ICSs

beclomethasone*, budesonide*, fluticasone*, mometasone*ciclesonide

corticosteroid conversions

quick mafs (equivalents will be given on exam)

ICS MOA

inhibit inflammation of the airways and modulate cytokine and chemokine production

LT receptor antagonists

Montelukast, zafirlukast

5-Lipoxygenase inhibitor

Zileuton

anti-IgE agent

omalizumab

IL-5 inhibitors

(MR. B)

mepolizumab

reslizumab

benralizumab

COPD risk factors

cigarette smoking

alpha 1-autitrypsin

Chemical factors for beta2 selectivity

bulky substituent

proper phenyl ring (resorcinol, salicyl alcohol, N-formamide)

Levalbuterol

(R)-isomer of albuterol

factors determining length of action

longer, bulkier, more lipophilic chains will act longer by resisting COMT and MAO metabolism

active enantiomer of olodaterol

R enantiomer

corticosteroid prodrug tells

Ester @ C-17 or 21

Ketone @ C-11

methylxanthine base structure

major enzyme in methylxanthene breakdown

xanthine oxidase

active chemical group of zileuton

N-hydroxyl group

LT receptor antagonists SAR

acidic or negative group

at least three aromatic rings (hydrophobic regions)

threshold for reversibility of airflow limitation

12% increase

Asthma control assessment

Daytime asthma symptoms more than 2x per week

Nighttime waking due to asthma

Reliever used more than 2x per week

Activity limitations from asthma

(0 = well controlled / 1-2 = partially controlled / 3-4 = uncontrolled)

Constant assessment in asthma patients

INHALER TECHNIQUE

Step up criteria

Uncontrolled asthma or risk of exacerbation

asthma step down criteria

consider when well controlled more than 3 months

PA - Step 1/2 initiation criteria

symptoms <4-5 days per week

PA/AA - step 3 initiation criteria

symptoms most days OR

Night awakening more than once per week

PA/AA - step 4 initiation criteria

Step 3 + low lung fxn (read absolutely fucked)

AA - step 1 initiation criteria

Sx < 2x per month

AA - step 2 initiation criteria

symptoms 2 or more times per month but less than 4-5 times per week

PA - step 1/2 therapy

low dose ICS/formoterol PRN

PA - Step 3 therapy

low dose ICS/formoterol maintenance and PRN

PA - Step 4 therapy

Medium dose ICS/formoterol maintentance and low dose ICS/formoterol PRN

PA - Step 5 therapy

Add LAMA to step 4 therapy

AA - step 1 therapy

SABA + ICS prn

AA - step 2 therapy

Low dose ICS maintenance + SABA PRN

AA - step 3 therapy

Low dose ICS/LABA maintenance + SABA PRN

AA - step 4 therapy

medium/high dose ICS/LABA maintenance + SABA PRN

AA - step 5 therapy

Add LAMA to step 4 therapy (Trelegy only asthma approved triple therapy)

Symbicort low dose

160/4.5 - 1 puff QD or BID

Symbicort medium dose

160/4.5 - 2 puffs BID

Symbicort reliever dose

160/4.5 - 1 puff PRN

Max daily Symbicort dose

12 puffs daily max

Asthma diagnostic criteria

1. history of respiratory symptoms AND

2. variable expiratory airflow limitation

measurement device for airflow

Spirometer

Atopic triad

1. dermatitis

2. allergic rhinitis

3. asthma

ICS Counselling Points

Rinse mouth and spit with maintenance doses to reduce risk of oral candidiasis

may cause hoarseness of voice

2 weeks for clinical effects

syndrome occurring with coadministration of strong CYP3A4 inhibitors and high doses of ICS

Cushing syndrome

LABA BBW

Do NOT use without ICS

• increased asthma related death -- yay!

SAMA/SABA asthma indication

only to be used for acute exacerbations in the hospital setting

Only asthma approved single-agent LAMA

Spiriva (tiotropium)

post-injection monitoring time for Omalizumab

first three months -- 2 hours then 30 minutes every visit after

IL-4 antagonist (dupilumab) AE

injection site pain

transient blood eosinophilia

Possible LTRA uses

asthma patients with…

1. allergic rhinitis

2. aspirin sensitivity

3. exercise-induced asthma

Asthma therapy follow-up

2-6 weeks after initiation of therapy then 3-12 months after controlled

targeting stepdown: every three months

exacerbation: 1 week followup

pharmaceutical aerosol definition

a pressurized dosage form that is released in a fine dispersion

pharmaceutical aerosol ingredients

1. product concentrate

2. propellant

Propellant pressure range (room temp [70 F])

10-15 PSI

Propellant requirements

"propellant should not be noticable in the suspension”

Aerosol propellants

hydrocarbons

hydrochlorofluorocarbons

hydrofluorocarbons

compressed gasses

two-phase aerosol system

1. liquid phase

2. product concentrate

three-phase aerosol system

1. water immiscible propellant

2. Aqueous product concentrate

3. Vapor phase

Compressed gas system

Product insoluble in gas

main advantage of inhaled vs systemic corticosteroids

increased bioavailability in lungs/lack of systemic adverse effects.

factors for particle distribution

1. particle size*

2. velocity of inspiratory flow

ideal particle size

1-5 microns

problem with large particles

fall out of the air quicker / stop upon initial impact (often before the lungs)

problems with small particles

move too easily → get exhaled as if a gas

percentage of medication reaching the lungs

10-20%