DPT IV Exam 2 (garner)

clinical presentation (hallmark symptoms) of asthma

cough

dyspnea

wheezing

chest tightness

diagnostic criteria for asthma

typical features of asthma symptoms:

-presence of > 1 of the hallmark symptoms

-worse at night or on waking

-vary over time and in intensity

-triggered by triggers

physical exam:

-breath sounds

-concurrent diseases

spirometry (>5 years of age)

-decreased FEV1

-≥ 12% improvement with bronchodilator

when is asthma typically diagnosed?

in early childhood

true or false: asthma control and severity waxes and wanes over time with age

true

course of asthma in those 0-4 years old

wheezing with respiratory infections without symptoms in between

course of asthma in those 5-12 years old

symptoms during day-to-day functions and increased risk of severe exacerbations compared with adults

describe the course of asthma

lifelong in 30-40% while 30-70% improve or become symptom-free as adults

true or false: asthma mortality is avoidable if adequately assessed and treated

true

what is the underlying cause of the symptoms of asthma (one word only)?

inflammation

name the 4 hallmark symptoms of asthma

wheezing, chest tightness, dyspnea, coughing

are the symptoms of asthma usually reversible?

yes

true or false: some children with asthma will improve or be symptom-free as asults but some will have persistent disease.

true

name 3-drug related risk factors for asthma-related deaths

not currently using or poor adherence with inhaled corticosterioid (ICS)-containing meds

currently using or recently stopped using oral corticosteriods (OCS)

(indicating the severity of recent events)

over-use of SABAs, especially if more than 1 canister/month

what are risk factors for dying from asthma?

H/O respiratory failure

anxiety/depression

recent hospitalization

H/O ED visit for asthma

overuse of SABA

not using ICS

no action plan

name 2 drugs that can trigger asthma symptoms in susceptible individuals

aspirin, beta blockers

true or false: diagnosis of asthma is primarily based on a good history of recurrent symptoms and spirometry (in adults and children > 5 years)

true

non-pharmacologic interventions for controlling asthma

smoking cessation/avoidance

physical activity

avoid occupational exposure

avoid medications that may worsen asthma

avoidance of indoor allergens

avoidance of outdoor allergens/air pollutants

treatments/evaluation for what comorbid conditions could help with the treatment of asthma?

allergic rhinitis/sinusitis/nasal polyps

food allergy and anaphylaxis

GERD

aspirin-exacerbated respiratory disease

infections

obesity

obstructive sleep apnea

chronic stress/depression/anxiety

what are the three categories of asthma medications?

controllers, relievers (rescue), and add-on therapies

controller asthma medications

inhaled corticosteroids (ICS)

ICS-long-acting-B2-agonist (LABA)

leukotriene modifiers

relievers/rescue asthma medications

ICS + formoterol

short-acting-B2-agoist (SABA)

ipratropium

systemic corticosteriod "burst"

add-on asthma medications

long-acting antimuscarinics (LAMA)

azithromycin

anti-IgE

anti-IL-5/5R

anti-IL-4R alpha

anti-thymic stromal lymphopoeitin

systemic corticosteroids (QOD, QD)

MOA of corticosteroids

binds to the glucocorticoid receptor and increases protein synthesis of beta2 receptors

decreases protein synthesis of cytokines, adhesion molecules (inflammatory modulators)

inhaled corticosteroids (ICS)

budesonide (Pulmicort Flexhaler, Pulmicort Respules)

fluticasone propionate (Flovent Diskus, ArmonAir RespiClick)

fluticasone furoate (Arnuity Ellipta)

mometasone (Asmanex Twisthaler)

beclomethasone (QVAR Redihaler)

ciclesonide (Alvesco)

fluticasone (Flovent HFA)

mometasone (Asmanex)

pharmacodynamics of ICS

onset → 1 to 2 weeks

peak → 4-8 weeks, up to 1 year

high topical: systemic effects

flat dose-response curve

what may increasing the dose of ICS lead to?

unwanted effects

adverse effects of ICS

dry, sore throat, dysphonia, thrush

decreases growth (benefits outweigh transient risk)

HPA axis suppression (at high doses)

osteoporosis

what helps decrease the adverse effects using ICS?

spacing/holding chamber, rinsing the mouth (rinsing not generally needed with as need low dose ICS-formoterol)

what dose is preferred with ICS?

the lowest possible dose

what is the most effective controller class for most patients?

inhaled corticosteroids

benefits of ICS

decreased asthma symptoms

increased lung function

improve quality of life

decrease frequency and severity of asthma exacerbations, hospitalizations, and death

MOA of long acting-B2 agonists (LABA)

activate B2 receptor, increasing cAMP and decreasing intracellular smooth muscle cell calcium

combination ICS-LABA

fluticasone-salmeterol (Advair)

budesonide-formoterol (Symbicort)

mometasone-formoterol (Dulera)

fluticasone-vilanterol (Breo Ellipta)

pharmacodynamics of long-acting B2 agonists (LABA)

onset → in ~ 20 minutes (salmeterol)

vs.

onset → in~ 5 minutes (formoterol and vilanterol)

peak 3 hours

duration of → 12 hours (salmeterol and formoterol)

duration of → 24 hours (vilanterol)

adverse effects of long-acting B2 agonists (LABA)

headaches, cramps

tachycardia, tremor, hypokalema

tolerance with regular use

severe asthma exacerbations

why was the black box warning for LABAs removed?

due to follow-up prospective studies required by the FDA

true or false: in children 4-11 years old and adults/adolescents, the safety of adding LABA to ICS vs. ICS alone was similar

true

should LABAs be used without ICS?

no

there is an increased risk of exacerbations

benefits of LABAs in combination with ICS

decreases asthma symptoms

increases lung function

decreases exacerbations

MOA of leukotriene modifiers

interfere with the pathway of leukotriene mediators

leukotriene modifiers

montelukast (Singulair)

zafirlukast (Accolate)

zileuton (Zyflo)

pharmacodynamics of leukotriene modifiers

full clinical effect in ~ 1 week

steroid-sparing

shifts dose-response (only) to aspirin

exercise-induced bronchospasm

pharmacokinetics of leukotriene modifiers

absorption rapid

cytochrome p450

elimination primarily through bile

drug interactions with leukotriene modifiers

zileuton increases teophylline levels, increased PT with warfarin

zafirlukast increases PT with warfarin

phenobarbital decreases montelukast levels

adverse effects of leukotriene modifiers

increases LFTs, decreases WBC (1° zileuton)

URI, fever, pharyngitis, cough, headache

otitis media, influenza, sinusitis

diarrhea, abdominal pain

hypersensitivity

neuropsychiatric events

black box warning of montelukast (Singulair)

mental health side effects

when should you stop montelukast and discuss with a health care professional?

mental health issues arise

leukotriene modifiers vs. ICS

less effective than ICS as initial controller but may be appropriate for patients who:

-"are unable or unwilling to use ICS"

-"experience intolerable side effects from ICS"

-have concurrent allergic rhinitis

true or false: leukotriene modifiers are less effective than LABA in combination with ICS

true

true or false: the LABAs all have similar onsets of action

false

true or false: there are significant differences among the ICS regarding effectiveness and ADEs

false

true or false: increasing ICS above low doses adds a substantial increase in effectiveness

false

true or false: leukotriene modifiers work as well as ICS

false

name advantages of montelukast over other leukotriene modifiers

dosage forms available

indicated in a wide age range

fewer ADEs

fewer drug-drug interactions

no restrictions about timing of administration with meals

relievers: short-acting β2-agonists (SABAs)

albuterol (ProAir® RespiClick, ProAir® Digihaler™)

albuterol (Ventolin® HFA, ProAir® HFA, Proventil® HFA)

levalbuterol (Xopenex® HFA)

albuterol (AccuNeb®)

levalbuterol (Xopenex®)

terbutaline (injectable)

pharmacodynamics of SABAs

onset within minutes

peak 30-60 minutes

duration 4-6 hours

intensity/duration are dependent on dose and severity of symptoms

adverse effects of SABAs

tachycardia, tremor, hypokalemia

tolerance with regular use

loss of asthma control with regular use

clinical pearls of SABAs

fastest, most effective bronchodilator reliever

relative safety of levalbuterol has not been proven (unless a lower relative dose is administered)

reliever: ipratropium (Atrovent® HFA) clinical pearls

add on to SABA in moderate-severe exacerbations in the ED setting (not continued if hospital admission) with modest benefits:

↑ lung function

↓ need for hospital admission

alternative to SABA for patients with intolerable ADEs (tachycardia, arrhythmia, tremor)

systemic corticosteroids used as relievers

Prednisone*

Prednisolone* (Orapred®, Pediapred®, etc.)

Methylprednisolone* (Medrol®, SoluMedrol®)

Dexamethasone (Decadron®)

*=strongest recommendations

PD and AEs of systemic corticosteroids

PD

onset 3 hours (so start ASAP)

peak 6-12 hours

AEs

-increased glucose, appetite, blood pressure

-mood alterations (e.g., psychosis), insomnia

which of the systemic corticosteroids have a horribllleeeee taste and the liquid formulations aren't best for kids?

prednisone

dexamethasone

prednisolone tastes good :)

true or false: I.V. administration of b2-agonists provides the fastest onset of action

false

true or false: albuterol should be prescribed as a scheduled maintenance regimen for asthma

false

true or false: albuterol's bronchodilation always lasts 4 hours

false

name 3 reasons why tachycardia is an adverse effect seen with b2-selective agonists.

they are b2-selective, not specific so could have b1effects (i.e., tachycardia) especially at high doses.

there are some b2-receptors in the heart which would cause tachycardia.

vasodilation in the peripheral vascular beds leading to reflex tachycardia

true or false: like other anticholinergics, ipratropium causes delirium, tachycardia, and decreased GI motility

false

true or false: currently, ipratropium is only recommended in asthma as a scheduled controller medication

false

what is the typical duration of a prednisone or prednisolone burst for an asthma exacerbation?

3-7 days

do patients require a dose taper after an OCS burst (yes or no)?

no

true or false: any liquid OCS dosage form is typically acceptable for children

false

MOA of LAMA

inhibits acetylcholine → bronchodilation

LAMA and ICS-LABA-LAMA combination

LAMA

tiotropium

(Spiriva Respimat®)

ICS-LABA-LAMA combination

fluticasone-vilanterol-umeclidinium

(Trelegy Ellipta®)

among whom is LAMA an add-on for?

patients ≥ 6 years old uncontrolled despite medium dose ICS-LABA

how old do you have to be to use a "triple inhaler"?

≥ 18 years old

benefits of LAMA and and ICS-LABA-LAMA combination

-increased lung function

-longer time to exacerbation

role of azithromycin in asthma

add-on for adult patients uncontrolled despite high dose ICS-LABA

benefits may include:

•↓ exacerbations

•↑ quality of life

before starting, ECG and sputum should be checked for atypical mycobacteria and risk of resistance for patient and population considered

Omalizumab (Xolair®)

add-on for patients ≥ 6 years old with moderate or severe allergic asthma and elevated IgE levels that are uncontrolled on Step 4-5 treatment

benefits may include:

•↓ symptoms and need for relievers

•↓ exacerbations and hospitalizations

•lower doses of oral steroids

Mepolizumab (Nucala®) and Reslizumab (Cinqair®)

block IL-5

Benralizumab (Fasenra®)

blocks IL-5 receptor and triggers eosinophil apoptosis

at what age is add-on therapy of Mepolizumab (Nucala®) for with severe eosinophilic asthma that are uncontrolled despite Step 4-5 treatment?

≥ 6 years old

at what age is add-on therapy of Reslizumab (Cinqair®) for with severe eosinophilic asthma that are uncontrolled despite Step 4-5 treatment?

≥ 12 years old

at what age is add-on therapy of Benralizumab (Fasenra®) for with severe eosinophilic asthma that are uncontrolled despite Step 4-5 treatment?

≥ 18 years old

benefits of IL-5/5R Inhibitors

•↓ symptoms

•longer time to exacerbations

•↓ daily oral steroid requirement

Dupilumab (Dupixent®)

add-on for patients ≥ 6 years old with severe asthma with eosinophilic phenotype or requiring treatment with OCS

benefits may include:

•↓ symptoms

•Longer time to exacerbations

•↓ daily oral steroid requirement

Tezepelumab-ekko

add-on for patients ≥ 12 years old with severe asthma with severe exacerbation in last year. no requirement for specific phenotype (i.e., no requirement for elevated eosinophils or IgE levels)

benefits may include:

•↓ exacerbations

•↓ ED visits, urgent care, or hospitalizations

•improved symptoms, lung function, and QOL

summary of the biologic: Omalizumab (Xolair®)

class

anti-IgE

age indicated

≥ 6 years

asthma indication

severe allergic asthma

summary of the biologic: Mepolizumab (Nucala®)

class

anti-IL5

age indicated

≥ 6 years

asthma indication

severe eosinophilic/type 2 asthma

summary of the biologic: Reslizumab (Cinqair®)

class

anti-IL5

age indicated

≥ 18 years

asthma indication

severe eosinophilic/type 2 asthma

summary of the biologic: Benralizumab (Fasenra®)

class

anti-1L5R

age indicated

≥ 12 years

asthma indication

severe eosinophilic/type 2 asthma

summary of the biologic: Dupilumab (Dupixent®)

class

anti-IL4R

age indicated

≥ 6 years

asthma indication

severe eosinophilic/type 2 asthma, or maintenance OCS

summary of the biologic: Tezepelumab (Tezspire®)

class

anti-TSLP

age indicated

≥ 12 years

asthma indication

severe asthma

ADEs of the biologics

injection site reactions, anaphylaxis

adverse effects of systemic corticosteroids

increased blood pressure, glucose, and appetite

ulcers, GI bleed

Cushingoid signs, cataracts, myopathy

decreased immunity, growth, bone density

hypothalamus-pituitary-adrenal (HPA) axis suppression

what is the last resort add-on therapy?

systemic corticosteroids

lowest possible dose and every other AM preferred

name 3 disadvantages of the add-on biologic therapies

cost, route of administration, risk of anaphylaxis

true or false: for chronic oral steroid therapy as a controller medication, BID dosing will provide greater efficacy and fewer side effects than qd or qod dosing

false

symptom control in treatment of asthma

-few asthma symptoms

-no sleep disturbance

-no exercise limitation

risk reduction in control of asthma

-prevent asthma-related death

-prevent exacerbations (flare-ups)

-maintain normal lung function

-avoid medication side effects

preferred starting treatment for adults and adolescents (12 and older) with asthma consists of what regimen?

controller and preferred reliever of prn ICS-formoterol