Asthma Flashcards
Asthma
Sense of breathlessness and tightness of chest
wheezing, dyspnea, cough
cause: immune-related airway inflammation
events leading to inflammation and bronchoconstriction
1) Allergen molecule binds to IgE on mast cells
2) Mast cells release mediatotors
–> bronchocontrictions
–> infiltration of inflammatory cells
3) inflammatory cells release more mediators
RESULT: airway inflammation characterized by edema, mucus plugging, smooth muscle hypertrophy = airflow obstruction
4) inflammation cause by bronchial hyperactivity
COPD symptoms result from 2 processes
1) Chronic bronchitis
- cough, excessive sputum
- hypertrophy of mucus-secreting glands in epithelium of large airways
2) Emphysema
- enlarged airspace within bronchioles and alveoli
- deterioration of walls of air spaces
Both caused by rxn to cigarette smoke
Major Drugs for Asthma and COPD: 2 classes
1) Antiinflammatory agents
Glucocorticoids: admin on fixed schedule
2) Bronchodilators
B2 aagonist: fixed schedule or as needed
- inhaled
Benefits of inhalation
direct to site of action
systemic effects minimized
rapid relief of acute attacks
Glucocorticoid drugs
Beclomethasone (inhaled)
Prednisone (PO prototype)
- most effective for long term control of airway inflammation
Beclomethasone (inhaled)
Prednisone (PO prototype)
Mechanism
decrease synthesis and release of inflammatory mediators (leukotrienes, histamines, prostaglandins)
Decreased infiltration and activity of inflammatory cells (eosinophils, leukocytes)
Decreased edema of airway mucosa
Beclomethasone (inhaled)
Prednisone (PO prototype)
Therapeutic use
control inflammation in both asthma and COPD
effective for asthma prophylaxis and management of COPD exacerbations
don’t alter course of conditions
- provide management of symptoms
inhalation use: very effective, fist line therapy
Prednisone (PO prototype) use
when symptoms cant be controlled with inhaled meds
moderate to severe asthma
high potential for toxicity
- treat brief as possible
Beclomethasone (inhaled)
Adverse effects
inhaled - devoid of serious toxicity
- high doses: oropharyngeal candidiasis (thrush), dysphonia (speaking difficulty)
- long-term high dose: adrenal suppression ( adrenal glands don’t make enough cortisol)
Prednisone (PO prototype) adverse effects
prolonged therapy: adreanal suppression, osteoporosis, immunosuppression
KEY: transferring from PO to inhaled requires several months for recovery of adrenocortical function
Beclomethasone (inhaled)
preparations
regular schedule
Prednisone (PO prototype) prepations dose and administration
methylprednisone, prednisone are preferred
adult dose 40-60 mg/day for 3-10 days
children: lower
Leukotriene receptor antagonists (LTRAs)
suppress leukotriene
- leukotriene involved in recruitment of eosinophils and other inflammatory cells
Types of LTRAs
Zileuton
- blocks leukotriene synthesis
Montelukast
- block leukotriene receptor
Leukotrienes
promote smooth muscle contraction, vessel permeability and inflammation
Zileuton mechanism
effects not immediate
inhibits enzyme that converts arachidonic acid into leukotrienes
Zileuton pharmacokinetics
PO, rapid absorption
Zileuton Adverse effects
Liver injury, possible hepatitis
Neuropsychiatric effects
montelukast: three indications
1) prophylaxis and maintenance in asthma
2) prevention of exercise-induced bronchospasm
3) relief of allergic rhinitis
montelukast mechanism
high affinity for leukotriene receptors
montelukast pharmacokinetics
PO rapidly absorbed
Metabolised in liver
Excreted in bile
Mast cell Stabilizer drug
Cromolyn
Cromolyn
Inhalation agent that suppresses bronchial inflammation
Prophylaxis in patients with mild to moderate asthma
Used when glucocorticoids cause problems
- not as effective as glucocorticoids
Mech of Cromolyn
Stabilizes mast cells
- prevent release of histamines
- inhibits eosinophils and macrophages
cromolyn pharmacokinetics
administrered by nebulizer
excreted unchanged in urine
Cromolyn therapeutic uses
Maximal effects take weeks to develop
prophylaxis for season allergy attacks
Administer 10-15 prior to exercise
Cromolyn Adverse effects
safest of all anti-asthma medications
preparation , dosage and administration of cromolyn
adults/children: 20 mg 4x/day
maintenance= lowest effective dose
Monoclonal Antiboides
form newest drug for airway inflammation
non are approved for first-line agents and for management of acute asthmatic episodes
IgE Antibody Antagonist
Omalizumab
three categories of monoclonal antibodies
1) IgE Antibody Antagonist
2) Interleukin-5 Antagonist
3) Interleukin-4 Receptor Alpha Antagonist
Omalizumab
Second-line agent
Omalizumab mechanism of action
-forms complexes with IgE in blood
= reduced available IgE
= limits availability of allergen to trigger release of histamine
therapeutic use of Omalizumbab
when asthma is allergy-related
or can’t be controlled by glucocorticoid
only for patients with a specific allergen
Omalizumab pharmacokinetics
administration: subQ injection
absorbtion: slow- peak levels in 7-8 days
half life 26 days
Omalizumab adverse effects
variety: injection site reaction, upper respiratory infection, sinusitis, pharyngitis
life-threatening anaphylaxis occurs rarely
preparations, dosage, administration omalizumab
powder reconstituted in sterile water
- then sub Q
dose and dosing interval determined by body weight and total serum IgE
Interleukin-5 Receptor Antagonist
Benralizumbab
Interleukin-5 (IL-5)
responsible for differentiation and maturation of eosinophils
mechanism of action Benralizumab
IL-5 receptor antagonists bind to IL-5 receptor
= inhibit
= reduced production of eosinophils
Therapeutic Use Interleukin-5 Receptor Antagonist
Restricted: only for severe eosinophilic asthma
Adverse effects of Benralizumab
SubQ injection: site of reaction, back pain
hypersensititivity
Interleukin-4 Receptor antagonist
Dupilumab
IL-4
Inflammatory cytokine that binds to many cells involved in inflammation
Mech of Dupilumab
its a monoclonal antibody (made in lab) that binds to IL-4 receptor
= decreased inflammatory response
Used for eosinophilic asthma
Dupilumab Adverse effects
SubQ injection site reaction, conjectivitis
Phosphodiesterase-4 inhibitor
Roflumilast
- approved for sever chronic COPD with a primary chronic bronchitis component
mechanism of Roflumilast
PDE4 breaks down cAMP
There fore PDE-4-inhibior = increased cAMP
cAMP reduces inflammation by suppressing cytokine release and decreasing pulmonary infiltration of neutrophils and other WBC
therapeutic use of roflumilast
not first line
prophylaxis for severe chronic bronchitis patients
adverse effects of roflumilast
the greatest concern is anxiety and depression to suicidal behavior
Bronchodilators
- Beta2- Andrenergic Agnosits
- Anti-Cholinergic
Beta 2- Andregnergic Agonists
Inhaled are most effective for acute bronchospasm and preventing EIB
Beta2- Andrenergic Agonists mechanism
Drug activates beta2-andrenergic recptors
- activated receptors in lung = bronchodilator
- limited role in suppressing histamine release
administration of bronchodilators
PO- long-term control, long-lasting, fixed schedule
- for asthma must be combined with glucocorticoid
INHALED
- short-acting (3-5hr)
- take before exercise to prevent attack
Anti-Cholinergic Drug name
Ipratropium
- approved only for COPDme
mechanism of Anti-cholinergic
blocks bronchi muscarinic receptors
= reduced bronchoconstriciton
- effects within 30 seconds, persist 6 hr
Therapeutic use Ipratropium
Inhalation
- system effects are minimal
Adverse effects of Ipratropium
dry mouth, irritation of pharynx
Combination Drugs
1) Glucocorticoid/ Long-Acting Beta2 Agonists
2) Beta2 adrenergic agonist/ Anticholinergic Combination
Glucocorticoid/Long-Active Beta 2 Agonsit Combination
- Anti inflammatory benefits of glucocorticoids
- bronchodilation of beta2 agonists
- for pt not controlled with inhaled glucocorticoid
- not first line
- black box
Beta 2- adrenergic agonist/ anticholinergic combination
- beta 2 agonist : bronchodilation by stimulating adrenergic receptors
- anticholinergic: brochodilation by blocking cholinergic receptors
Classification of asthma severity
1) intermittent
2) mild persistant
3) moderate persistent
4) severe persistent
what is severity of asthma classification based upon
impairment- quality of life, functional capacity
risk- adverse events
initial therapy for acute/severe exacertbation
- oxygen: hypoxemia
- systemin glucocorticoid: inflammation
- nebulized high-dose SABA: airflow obstruction
- Nebulized Ipratropium (anti-cholinergic): further reduce airflow obstruction
Stepwise managing asthma
1) inhaled SABA (short-acting beta agonist) as needed
2) ling-term control med = generally inhaled glucocorticoid
3) dosage increased or another medication is added
4) after a period of sustained control, move down a step is tried
drugs for acute/severe exacerbations goal of drugs
- relieve hypoxia
- relieve airway inflammation
- relieve airway obstruction
- normalize lung function
cause of exercise-induced bronchospasm (EIB)
loss of heat or water from lung
preventing EIB
inhale SABA (preferred)
Cromolyn (mast-cell stabilizer prophylactically
