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
activation of mast cells
infiltration of eosinophils
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
activate beta-2 receptor -> activate adenyl cyclase and increase cAMP -> smooth muscle relaxation
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
history of respiratory symptoms AND
variable expiratory airflow limitation
measurement device for airflow
Spirometer
Atopic triad
dermatitis
allergic rhinitis
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…
allergic rhinitis
aspirin sensitivity
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
product concentrate
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
liquid phase
product concentrate
three-phase aerosol system
water immiscible propellant
Aqueous product concentrate
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
particle size*
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%