Asthma Flashcards
Normal Value for FEV1
> 80%
Normal Value for FVC
Adults can empty 80% of air in 6 seconds
Normal Value for FEV1/FVC
Within 5% of predicted value (based on age, height, sex, gender)
Which spirometry test can be done at the patients home?
Peak Flow/ PEFR = Peak expiratory flow rate
Which Spirometry value determines if the disease is obstructive of restrictive
FEV1/FVC
what are obstructive diseases vs restrictive diseases of the lung
obstruct: asthma/COPD
restrict: pulmonary fibrosis
If the FEV1/FVC is low what kind of lung disease is it - obstructive or restrictive
obstructive
If the FEV1/FVC is normal what kind of lung disease is it - obstructive or restrictive
restrictive
If the FEV1/FVC is high what kind of lung disease is it - obstructive or restrictive
restrictive
Asthma or COPD - has DRY cough
asthma
Asthma or COPD - signs of atopy
asthma (atopy is basically allergies…)
Possible Asthma triggers
- Exercise
- Stress
- pets
- Emotions
- Pollution
- Insects/fecal matter
- Dust
How to Classify Asthma
Intermittent or Persistant
within Persistant - mild, moderate, severe
COPD - what 3 main factors cause the airflow limitation
- chronic bronchitis
- emphysema
- inflammation
Describe Emphysema
Abnormal enlargement of the airspaces in alveoli - leads to destruction of alveolar walls
- the structural changes/destruction of alveoli lead to REDUCED ELASTICITY
Definition of Chronic Bronchitis (number wise…)
Cough and Sputum production for at least 3 MONTHS in each of 2 CONSECUTIVE YEARS
Chronic bronchitis causes structural changes which will __________ the airways due to FIBROSIS
narrow
Inflammation in COPD - comes from irritants -
causes 2 things that will lead to making of fibroblasts
Oxidative stress (more oxidants) Protease - antiprotease imbalance (more proteases than antiproteases
Asthma or COPD - reversible
asthma
Asthma or COPD - irreversible
COPD
Hallmark symptoms of COPD
Chronic cough; dyspnea; SPUTUM PRODUCTION
Typically patient of COPD
> 40 years of age w/ common symptoms of COPD;
Hx of exposure to risk factors (smoke)
Family hx of COPD
COPD Signs
BARREL CHEST! Increase Resp. Rate Use of accessory muscles to breath Decreased breath sounds Prolonger Expiration Lips pursing on expiration
Particles that can cause COPD
CIGARETTE SMOOOOKE
Occupational dust/fumes
Indoor pollution
Spirometry is REQUIRED to diagnose _______
COPD
A post-bronchodilator FEV1/FVC has to be _______ to be diagnosed as COPD
< 0.7
Assessment Categories for COPD
- Spirometry
- Symptoms
- Exacerbation Risk
- Comorbidities
What do Inhaled beta agonists do
cause bronchodilation by relaxing bronchial smooth muscle
What are the SABAs (short acting beta 2 agonists)
Albuterol and Levalbuterol
What is the onset of action for SABAs
3 - 5 minutes
SABAs are best for _______ asthma symptoms
acute
Brand for Levalbuterol
Xopenex
Xopenex is what kind of asthma drug
SABA - short acting beta2 agonist (levoalbuterol)
What are the Long acting Beta 2 agonists (LABAs)
Salmeterol Formoterol Arformoterol Indacterol Olodaterol (there are combo products with inhaled corticosteroids and LAMAs)
What is the onset of action for LABAs (and peak effect time)
15 - 30 minutes - up to 3 hours for peak effect!!
Side effects of Beta 2 agonists for asthma
Hyped up pts = tachycardia, skeletal muscle tremors, palpitations
HYPOKALEMIA
HYPERGLYCEMIA
What is the Boxed Warning for LABAs
LABA canNOT be used as monotherpay for asthma patients!! Increased risk for asthma induced death
LABA monotherapy is OK for COPD patients tho
Brand: ?
Generic: Salmeterol
Serevent Diskus
Brand: ?
Generic: Formoterol
Foradil Aerolizer
Brand: ?
Generic: Arfomoterol
Brovana Nebulizer
Brand: ?
Generic: Indacterol
Arcapta Neohaler
Brand: ?
Generic: Olodaterol
Striverdi Respimat
Brand: Serevent Diskus
Generic: ?
Salmeterol
Brand: Foradil Aerolizer
Generic: ?
Formoterol
Brand: Brovana Neublizer
Generic: ?
Arformoterol
Brand: Arcapta Neohaler
Generic: ?
Indacterol
Brand: Striverdi Respimat
Generic: ?
Olodaterol
What are the SAMAs (short acting Antimuscarinics)
Ipratropium; Ipratropium + Albuterol
What are the LAMAs (long acting Antimuscarinics)
Tiotropium Umeclidinium Aclidinium Glycopyrrolate (there are combo products with LABAs)
Brand: ?
Generic: Tiotropium
Spiriva
Brand: ?
Generic: Umeclidinium
Incruse Elipita
Brand: ?
Generic: Aclidinium
Tudorza Pressair
Brand: ?
Generic: Glycopyrrolate
Seebri Nebulizer
Brand: Spiriva
Generic: ?
Tiotropium
Brand: Incruse Elipta
Generic: ?
Umeclidinium
Brand: Tudorza Pressair
Generic: ?
Aclidinium
Brand: Seebri Neohaler
Generic: ?
Glyccopyrrolate
remmeber this one bc seebri - like sebring and glyccopyrolate normally for GI -and mom has a sebring and GI issues…
Brand: ?
Generic: Ipratropium
Atrovent
Brand: ?
Generic: Ipratropium and Albuterol
Combivent
Brand: Atrovent
Generic: ?
Ipratropium
Brand: Combivent
Generic: ?
Ipratropium and Albuterol
If a COPD patient is Group A - how do you treat it?
bronchodilator —> try another class
If a COPD patient is Group B - how do you treat it?
Long acting bronchodilator –> LABA + LAMA
If a COPD patient is Group C - how do you treat it?
LAMA –> LABA + LAMA
can go to LAMA + ICS but try to hold off on ICS as much as possible in COPD pts
If a COPD patient is Group D - how do you treat it?
LABA + LAMA –> LABA + LAMA + ICS
Maybe Dalrisep or Macrolide Abx
An asthma patient that is intermittent will fall into Step ___ for asthma treatment
1
An asthma patient that is persistent - mild will fall into Step ___ for asthma treatment
2
An asthma patient that is persistent - moderate will fall into Step ___ for asthma treatment
3 or 4
An asthma patient that is persistent - severe will fall into Step ___ for asthma treatment
5 or 6
Asthma Treatment Guidelines:
Step 1
No control agent; Use SABA prn
Asthma Treatment Guidelines:
Step 2
Low ICS as control agent; SABA prn
Asthma Treatment Guidelines:
Step 3
Low ICS/LABA; SABA prn
Asthma Treatment Guidelines:
Step 4
Med or high ICS/LABA; SABA prn
Asthma Treatment Guidelines:
Step 5
Med or high ICS/LABA; SABA prn and maybe add on:
- tiotropium
- Anti-IgE
- Anti-IL5
Alternate Controller Options for Asthma:
When would a leukotriene modifier be utilized?
Steps 2 - 4
Alternate Controller Options for Asthma:
When would low dose oral corticosteroid be utilized?
Step 5
3 main treatment strategies for Asthma
Bronchodilation; anti-inflammation; Inhibit mast cell degranulation
Treatment strategies for Asthma:
What drugs are used for bronchodilation
- Beta2 agonists
- Anticholinergics
- Methylxanthines
Treatment strategies for Asthma:
What drugs are used for anti-inflammation
Glucocorticoids
Antileukotriene Agents
Treatment strategies for Asthma:
What drugs are used to inhibit mast cell degranulation
Cromolyn- like drugs
Xolair (Omalizumab)
what does LTRA stand for
leukotriene receptor antagonist
what does A1R stand for
adenosine receptor
what does CysLT stand for
cysteine leukotrienes
what does CystLT-1R stand for
cysteine leukotriene receptor
what does MAO stand for
monoamine oxidase
what does COMT stand for
catechol-O-methyltransferase
Sympathomimetic Amines aka
B2 adrenergic receptor agonists
Primary activity of sympathomimetic amines
relax bronchial smooth muscle
Secondary activities of sympathomimetic amines
inhibit release of mediators from mast cells, inhibit microvascular leakage, increase microcilliary transport of mucus
what pathway do B2 agonists stimulate/what is the pathway
they stimulate the GaS pathway - which increases the amount of cAMP –> more PKA –> PKA will phosphorylate MLCK to make it inactive –> causes relaxation
SABAs are resistant to (COMT/MAO/BOTH)
COMT
LABAs are resistant to (COMT/MAO/BOTH)
BOTH
Patients should not be using albuterol more than ____ times per week unless its for exercise induced asthma
2
inhalational drugs allow for more _____ action and fewer _______ effects
local; systemic
Adverse effects of Selective B2 adrenergic agonists
- tachycardia/palpitations
- skeletal muscle tremors
Glucocorticoid MOA:
alter __________ of proteins involved in the ______ process
gene expression; inflammatory
Glucocorticoid MOA:
what 3 type of cells will be found in the bronchial epithelium and submucosa and will be decreased via glucocorticoids
eosinophils, macrophages, mast cells
Glucocorticoid MOA:
will inhibit synthesis of what ________ and ________
prostaglandins; Leukotrienes
Glucocorticoids should not be used for patients under ____ years old
12
How does theophylline work to cause bronchodilation?
antagonizes the adenosine receptor and inhibits PDE4
What happens when the adenosine receptor is BLOCKED/antagonized by theophylline
the Gq pathway is NOT stimulated and not IP3/No Ca is released –> Myosin LC kinase does not work to activate myosin LC –> NO CONTRACTION
what happens when PDE4 is inhibited by theophylline
if PDE4 doesn’t work - cAMP is not made into AMP = more cAMP = more PKA = it will INHIBIT myosin LC kinase = no activated mysoin LC = no contraction = relaxation
why is theophylline not used as often anymore?
it has a narrow therapeutic range
the half-life of theophylline is _______ in patients with _________
increased; CHF
_________ will delay the absorption of theophylline
Mg and Al antacids
Theophylline may aggravate pre-existing __________
seizure disorders
What agents increase theophylline levels by competition
- cimetidine
- allopurinol
- erythromycin
- fluroquinolones
- propranolol
- leukotriene inhibitors (Zileutin)
primary use for theophylline
prevent asthma attacks
usual therapeutic range for theophylline
10 - 15 ug/mL
when do you start to see adverse effects of theophylline
20 ug/mL
Mechanism of Mast Cell degranulation process/what is needed
1- IgE Ab bind to FcR 2- binding of antigen to IgE Ab 3 - clustering of FcR receptors 4 - influx of Ca2+ via CRAC (Calcium released activated channels) 5 - ATP
Ways to Inhibit Mast Cell Degranulation
Cromolyn and Xolair
Cromolyn is very _____ (stable/unstable) but extremely _______ (soluble/insoluble)
stable; insoluble
Is cromolyn used to treat an attack or used as preventative?
preventative — can’t
re-granulate a mast cell…..
What is Xolair and how does it work
it is an anti-human IgE ab
Xolair will bind to IgE abs so that IgE cannot bind to the FcR1 receptors on mast cells
Xolair is indicated for who?
patients over 12 y.o with moderate - severe persistent asthma and has been unresponsive to inhaled steroids
xolair causes a 96% _______ in free _____ levels
reduction; IgE
Brand for Zileuton
Zyflo
what does Zileuton do
it is a selective inhibitor of 5-lipoxygenase –> inhibits synthesis of leukotrienes (LTB4, LTC4, LTD4)
Zileuton - for acute attack or nah?
nah
Zileuton is indicated for what?
the prophylaxis and treatment of chronic asthma
Zileuton will _______ the blood levels of theophylline
double
What are some Leukotriene inhibitors
Zieluton
Montelukast
Zafirlukast
Accolate is brand for?
Zafirlukast
how do zafirlukast/montelukast work?
the selectively and competitively inhibit CysLT1 receptor
zafirlukast/montelukast are known to inhibit the ____ phase of _________
late; bronchoconstriction
If zafirlukast/montelukast black the CysLt1R - what happens cellularly/in a pathway?
IF CysLt1R is inhibited - there is no Gq pathyway stimulated –> no IP3/Ca –> no muscle contraction
CysLT1R antagonists (aka zafirlukast/montelukast) are metabolized by the ______
liver
Food _______ the bioavailability zafirlukast/montelukast
reduces
zafirlukast/montelukast - (should/should not) be abruptly substituted for inhaled/oral corticoisteroids
should NOT
Drugs that are used to treat COPD
- inhaled antimuscarinic agents
- LABA
- SABA
(rare: a1 antitrypsin replacement)
Ipratropium and Tiotropium are antimuscarinics used for ______ - their structures are both _____________ which ______ systemic absorption
COPD; quaternary ammonium compound; decreases
___________ (Ipratropium or Tiotropium) has higher affinity and is more selective for the M1/M3 receptors
tiotropium
how do antimuscarinics works? (pathway etc…)
they BLOCK Ach from working @ M1/M3 receptors - prevents Gq pathway –> no IP3/No Ca –> No contraction
Iptratropium is given ______ time(s) per day
Tiotropium is given _____ time(s) per day
3 - 4; 1
used for COPD, Asthma, or Both?
Formoterol
both (but remember cannot use JUST a LABA in asthma!!!)
used for COPD, Asthma, or Both?
Salmerterol
both (but remember cannot use JUST a LABA in asthma!!!)
used for COPD, Asthma, or Both?
Indacaterol
COPD only
Remodeling in COPD - what kind of things occur
- fibrosis of small airways
- hyperinflation of lungs
- Alveolar enlargement/wall destruction (emphysema)
- mucus hypersecretion
what is the drug Ivacaftor?
it is a CFTR regulator - will potentiate Cl current through CFTR in response to cAMP
Adverse Events for ICS
oral thrush, cough, dysphonia (hoarse voice)
which ICS product has a built in spacer
Aerospan
Counseling tip for ICS
rinse and SPIT after use
Clinical pearl about pulmicort respules
should use Jet nebulizer and should not be mixed with other nebulizer solutions
want to titrate to the ________ effective dose because at ______ doses there is an increase for systemic side effects
lowest; high
Boxed warnings for LABA agents
1) monotherapy of LABA with asthma patients can increase risk of asthma related death
2) increasing hospitalization in pediatric and adolescent patients
adverse effects for LABA agents
tachycardia; headache; tremor; irritability
LABA agents: _______ seen with intentional overdoses
prolonged QT
LABA (may or may not) be useful for exercise induced bronchospasm
may
Taken once or twice a day?
brovana
twice
Taken once or twice a day?
foradil
twice
Taken once or twice a day?
arcapta neohaler
once
Taken once or twice a day?
striverdi respimat
once
Taken once or twice a day?
Serevent
twice
Taken once or twice a day?
Turdoze
twice
Taken once or twice a day?
Spiriva
handihaler - once
respimat - once
Taken once or twice a day?
Incruse ellipta
once
Taken once or twice a day?
QVAR
twice
Taken once or twice a day?
Budesonide DPI/Flexhaler
twice
Taken once or twice a day?
Alvesco
once
Taken once or twice a day?
Aerospan
twice
Taken once or twice a day?
Flovent
twice
Taken once or twice a day?
Armon Air
twice
Taken once or twice a day?
Arnuity Ellipta
twice
Taken once or twice a day?
Asmanex
twice for adults
Taken once or twice a day?
Budesonide nebulizer
once (divided dose maybe…)
Adverse effects of LAMA
dry mouth dizziness, blurred vision, upper RTIs; paradoxical bronchospasms
_______ (a antimuscarinic) has been approved for use in asthma as an add-on option in steps ___ or ____ (IF has Hx of exacerbations despite ICS and LABA use)
tiotropium; 4;5
Taken once or twice a day?
Advair
twice
Taken once or twice a day?
airduo
twice
Taken once or twice a day?
symbicort
twice
Taken once or twice a day?
dulera
twice
Taken once or twice a day?
Breo Ellipta
once
Taken once or twice a day?
Stiolto Respimat
once
Taken once or twice a day?
Anoro Ellipta
once
Taken once or twice a day?
Utibron Neohaler
twice
Taken once or twice a day?
Bevespi Aerosphere
twice
Adverse effects of SABAs
tachycardia; hypokalemia; skeletal tremors; irritability
May mix albuterol nebulizer solution with what other things?
cromolyn solution;
budesonide inhalant suspension; ipratropium solution
Levoalbuterol and albuterol comparison
levoalbuterol at 1/2 mg dose of albuterol will provide comparable efficacy and safety
Adverse effects of SAMAs
Dry mouth; urinary retention; infection; sinusitis; bronchitis
which is first line therapy for severe exacerbations?
albuterol or ipratropium
albuterol
Adverse effects of systemic corticosteroids
short term use: Hyperglycemia; increased appetite; fluid retention; demargination of WBCS; psychiatric disturbances;
Drug interactions with oral corticosteroids
warfarin INR increases; efficacy of vaccines decreases
can oral corticosteroids and ICS be used together?
yes if ICS was being used before hospital exacerbation
contraindications of oral corticosteroids
systemic fungal infections; administration of live vaccine
why are “bursts” of oral corticosteroids used
to establish control when initiating therapy or during period of gradual deterioration
when can you do an injection of systemic corticosteroids
injection may be used in place of burst if adherence or vomiting is an issue
main causes of exacerbations
RTIs; Air pollution; unknown;
how to treat an exacerbation
1) short acting bronchodilators and Systemic Corticosteroids
(albuterol/ipratropium and prednisone 40 mg x 5 days)
2) Abx if CARDINAL SX PRESENT
what abx are typically used for treating the cardnial symptoms of an exacerbation
macrolides; tetracyclines; amoxicillin/clauvulanate;
how long are abx typically used for treating the cardnial symptoms of an exacerbation
5 - 7 days
Cardinal Symptoms needed in order to give Abx to an exacerbation patient
sputum purulence; sputum volume; dyspnea
need all 3 or at least 2 and one of them mst be sputum purulence
Pathogenesis of Asthma:
Early reaction
early - IMMEDIATE bronchoconstriction
antigen binding to IgE Abs will release contents from mast cells/bronchial smooth muscle contraction/vascular leakage
Pathogenesis of Asthma:
Delayed Reaction:
2 - 8 hours
- sustained bronchoconstriction
- activation of TH2 lymphocytes
- mucus hypersecretion
- cellular infiltration
when TH2 lymphocytes get activated during the delayed reaction of asthma - what is released
GM-CSF; IL-4; IL-5; IL-13
pathophysiology of asthma:
PAF = platelet activating factor and it causes what?
hyper-responsiveness
pathophysiology of asthma:
ECP = eosinophil cationic protein - what is it?
cytotoxic and a marker of inflammation
what is periostin?
a matrix protein biomarker
how does hypersecretion of mucus in asthma happen?
TH2 cells release cytokines –> cytokines causes hyperplasia of goblet cells –> hypersecretion of mucus
Hypersecretion of asthma:
what molecule causes the maintenance of hyperplasia?
Bcl-2
Hypersecretion of asthma:
what molecule causes the development of hyperplasia
EGFR; CLCA
Genetics and Goblet Cell Hyperplasia
IL-4a can have a mutation where Q576 becomes R576 this causes an enhanced response to IL-13;
~50% of African Americans are homozygous for R576 in IL-4a
_________ promotes chronic allergic inflammation in response to Th2 cytokines
Periostin
Airway Remodeling in Asthma:
what happens to the EPITHELIUM?
mucous hyperplasia and hypersecretion
Airway Remodeling in Asthma:
what happens to the basement membrane?
thickening
Airway Remodeling in Asthma:
what happens to the smooth muscle
hypertrophy
Remodeling in COPD: \_\_\_\_\_\_\_ of small airways \_\_\_\_\_\_\_\_ of lungs Alveolar \_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_ hypersecretion
fibrosis; hyperinflation; enlargement; wall destruction; mucus
why is a deficiency of alpha-1-antitrypsin bad for COPD pts?
NORMALLY alpha-1-antitrypsin INHIBITS neutrophil elastase and limits lung tissues damage
What is a cardinal early sign of cystic fibrosis?
excessively salty sweat
Loss of CFTR function in airway epithelium causes _________
thickening of mucus because of dehydrated ASL (airway surface liquid)
Lumen of Sweat Duct - how does it normally operate
CFTR brings Cl- into the cell and Na+ also comes into the cell via ENaC
2 main inflammatory mediators that will stimulate the Gq/IP3/Ca/Contraction pathway
LTC4/LTD4 and Histamine
Serum Levels of Theophylline and Adverse effects seen there:
20 ug/mL
20 ug/mL - nausea/vomiting/nervousness
/abdominal cramping
Serum Levels of Theophylline and Adverse effects seen there:
> 25 ug/mL
cardiac arrythmias; hypotension; CNS stimulation
Serum Levels of Theophylline and Adverse effects seen there:
40 - 100 ug/mL
seizures/CV arrest
what dosage forms does theophylline come in?
ER tablet; ER Capsule; Liquid
Adverse effects of Theophylline
(THINK OF COFFEE!!) insomnia; GI upset; hyperactivity; hypotension
Dose related toxicities of Theophylline (according to Miller)
Tachycardia; nausea; vomiting; headache; seizures; arrhytmias
Contraindications of theophylline
- peptic ulcers disease
- Arrhythmias
- seizure disorders
Drug interactions of theophylline:
Theophylline is a major _______ for what CYP enzyme(s)
substrate; 3A4; 1A2; 2E1
Drug-Interactions of Theophylline:
will increase the concentration of what drugs?
- cimetidine
- erythromycin
- clarithromycin
- ciprofloxacin
- ticlopidine
Miller’s target range for theophylline
5 - 15 mcg/mL
Drug-Interactions of Theophylline:
will decrease the concentration of what drugs?
- phenobarbitol
- phenytoin
- carbamazepine
- rifampin
- smoking
_____________ is likely the cause for hypotension/tachycardia/nausea seen from theophylline
PDE III inhibition
For COPD or Asthma?
Daliresp
COPD
things to monitor with Daliresp
Liver function tests; Weight
Adverse effects of Xolair
- Headache
- injection site reactions
- arthralgias
- thrombocytopenia
- pharyngitits
- sinusitis
- upper RTIs
Xolair: Do not administer more than _______ per injection site
150 mg
Who is Xolair FDA approved for?
moderate - severe asthma patients w/ a positive skin test/reactivity in a perennial aeroallergen and Sx that are inadequately controlled with ICS
Adverse events for Nucala
- headache
- infection site reactions
- arthralgias
- Herpes Zoster infection
when is Nucala used for an add-on maintenance treatment?
when the patient has severe asthma with an EOSINOPHILIC phenotype
when is Cinqair used for an add-on maintenance treatment?
when the patient has severe asthma with an EOSINOPHILIC phenotype
Adverse events of Cinqair
- injection site reactions
- myalgias
- increased creatine phosphokinase
Which monoclonal Ab has a boxed warning for malignancies?
Cinqair
Formoterol or Salmeterol?
Which one has a longer duration? and why
Salmeterol - it has more lipophilcity
Formoterol or Salmeterol?
Which one has the greater receptor affinity?
Salmeterol
Formoterol or Salmeterol?
Which one has greater water solubility/moderate lipophilicity?
formoterol (will have shorter duration of action)