Asthma Flashcards
Asthma Triggers
- Environment
- Respiratory infection
- Allergens
- Emotions
- Exercise
- Drugs/preservatives
- Occupational stimuli
What are the most important asthma triggers?
Environmental:
Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco smoke, wood smoke
Define Asthma
Widespread, reversible narrowing of bronchial airways w/marked increase in bronchial responsiveness to inhaled stimuli
Asthma: pathophysiology of bronchoconstriction
- Irritant stimulates vagal nerve pathways –> postganglionic fibers release acetylcholine at muscarinic receptors on bronchial smooth muscle cells –> BRONCHOCONSTRICTION
- Irritant also stimulates release of chemical mediators from mast cells in lungs –> BRONCHOCONSTRICTION
Diagnostic criteria: asthma
- Detailed med Hx
- PE
- Spirometry (age ranges, but typically FEV1/FVC <70% is a problem)
Components of severity classification: asthma
- Frequency of symptoms
- Nighttime awakening
- Days/wk SABA used for Sx control
- Interference w/normal activity
*use the highest classification
Intermittent or Persistent (mild, moderate, severe)
Asthma treatment goals
Reduce impairment: prevent chronic & troublesome Sx; prevent frequent use of rescue meds, 2+/week; maintain near normal pulmonary function & normal activity
Reduce Risk: prevent hosp, prevent loss lung fx, provide optimal pharm w/minimal AEs
Asthma medications
SHORT ACTING B2 AGONISTS
LONG ACTING B2 AGONISTS
INHALED CORTICOSTEROIDS
LEUKOTRIENE INHIBITORS
CROMOLYN (INTAL®)
METHYLXANTHINES
IMMUNOMODULATORS
ORAL CORTICOSTEROIDS (OCSs)
Most effective long-term control medication
Inhaled corticosteroids: reduces impairment and risk of exacerbations
B2 Receptor Agonists, Short Acting (SABAs): agents
- Albuterol (ProAir, Proventil)
- Levalbuterol (Xopenex)
- Pirbuterol (Maxair)
B2 Receptor Agonists, Short Acting (SABAs): MOA
selectively activate β-2 adrenergic receptors in the smooth muscles of the lungs, promoting bronchoconstriction
B2 Receptor Agonists, Short Acting (SABAs): indications
Indications: acute bronchospasm (“rescue inhaler”) and prevention of exercise-induced asthma
B2 Receptor Agonists, Short Acting (SABAs) and long acting (LABAs): ADRs
inhalation –> minimal systemic effects; tremors/shakiness
-oral –> possibility of activated β-1 receptors with high dose –> tachycardia; angina; tremors
significance of albuterol and levalbuterol as enantiomers
enantiomers are chemical mirror images; theoretically, levalbuterol may have a lower risk of bronchial hyperresponsiveness because it does not contain the S-isomer; however albuterol is still more frequently rx’ed due to the availability of a generic
Albuterol (ProAir, Proventil): onset & duration
Onset: ~10min, duration 3-4h
(SABA)
Albuterol (ProAir, Proventil): formulations
MDI, Neb
(SABA)
Albuterol (ProAir, Proventil): available generic?
Available generic, least $
SABA w/most and least clinical evidence
Most: Albuterol (ProAir, Proventil)
Least: Pirbuterol (Maxair) - least B2 potency
Levalbuterol (Xopenex): onset & duration
Onset: ~10min, duration 3-4h
Levalbuterol (Xopenex): formulations
MDI, Neb
Levalbuterol (Xopenex): available generic?
no
Pirbuterol (Maxair): onset & duration
Onset: ~30min, duration 5h
Pirbuterol (Maxair): formulations
MDI
Pirbuterol (Maxair): available generic?
no!
LONG-ACTING BETA-2 RECEPTOR AGONISTS (LABAs): agents
Salmeterol (Serevent)
Formoterol (Foradil)
LABAs: indication
indicated for long term control of asthma; preferred adjunctive therapy in combination with ICS
LABAs: BBW
LABA use alone can increase the risk of asthma-related death!; should ALWAYS be combined with an ICS
Salmeterol (Serevent): onset/peak, duration
up to 2h, Duration: 12h
Best clinical evidence for LABAs
Salmeterol (Serevent)
Salmeterol (Serevent): generic available?
Yes!
Formoterol (Foradil): onset/peak & duration
Onset/Peak: up to 2h, Duration: 12h
Formoterol (Foradil): formulations
Aerosol powder for inhalation
Formoterol (Foradil): generic available?
no
inhaled corticosteroids: agents
- beclomethasone dipropionate
- fluticasone
- mometasone furoate
Advair®, Symbicort® and Dulera® are combination corticosteroid + β-2 adrenergic agonist formulas
-SONE
inhaled corticosteroids: MOA
direct local anti-inflammatory activity; reduce airway hyperresponsivenes; inhibit inflammatory cell migration and activation
Inhaled/Oral corticosterois: ADRs
- inhalation –> oral candidiasis (use spacer and gargle afterwards); dysphonia
- intranasal –> drying; itching; sore throat; epistaxis
- systemic effects –> cataracts; glaucoma; hyperglycemia; PUD (oral only); bone loss; adrenal suppression
- slowed growth in children and adolescents
ICS: considerations for effectiveness
- Consider lung delivery % if delivery to site of action is an issue (think pediatric pts.) –> beclomethasone and flunisolide have highest lung delivery %
ICS: Special administration instructions
- Oral rinse with water after use
- Onset of improvement within 1 week of initiation –> tell pt. not to d/c after a few days of use
ICS: concerns w/systemic availability
- Systemic adverse effects
- ?Decreased growth velocity
ICS: monitoring parameters?
growth velocity in pediatrics – may ↓ GV if systemic absorption
LEUKOTRIENE INHIBITORS: MOA
interfere with the production of chemical mediators by eosinophils and mast cells –> ↓ plasma exudation, mucus secretion, bronchoconstriction and eosinophil recruitment
LEUKOTRIENE INHIBITORS: Indications
Indications: moderate to severe persistent asthma;
LEUKOTRIENE INHIBITORS: recommendations - when and with what
recommended in combination with high-dose ICS + LABA;
**considered prior to initiation of chronic corticosteroid therapy
LEUKOTRIENE INHIBITORS: agents
Leukotriene Receptor Antagonist:
- Montelukast (Singulair®)
Leukotriene Receptor Antagonist:
- Zafirlukast (Accolate®)
5-Lipooxygenase Inhibitor:
- Zilueton (Zyflo CR®)
Montelukast (Singulair®): dosing
4-10 mg PO QHS
Leukotriene Receptor Antagonist:
Montelukast (Singulair®): ADRs
*H/A (up to 25%)
Leukotriene Receptor Antagonist
Zafirlukast (Accolate®): dosing
10-20 mg PO BID
Leukotriene Receptor Antagonist
Zafirlukast (Accolate®): ADRs
transaminitis
Leukotriene Receptor Antagonist
Zafirlukast (Accolate®): C/Is
Hepatic impairment
Leukotriene Receptor Antagonist
Zilueton (Zyflo CR®): dosing
1200 mg PO BID
5-Lipooxygenase Inhibitor
Zilueton (Zyflo CR®): ADRs
transaminitis
5-Lipooxygenase Inhibitor
Zilueton (Zyflo CR®): C/Is
C/I: Hepatic impairment
also $$$
5-Lipooxygenase Inhibitor:
CROMOLYN (INTAL®): indication
alternative agent for mild persistent asthma –> effective in providing symptom control for exercise induced bronchospasm (EIB); inferior to ICS in improving outcomes
CROMOLYN (INTAL®): dosing & formulations
MDI or nebulizer; 20 mg inhalation up to 4 times daily
CROMOLYN (INTAL®): MOA
MOA: mast cell stabilizer
CROMOLYN (INTAL®): Onset of response to therapy
2 to 6 weeks
CROMOLYN (INTAL®): ADRs
Good tolerability and safety profile
METHYLXANTHINES: Agents
only theophylline (Elixophyllin ®)
METHYLXANTHINES: Indications
alternative step up therapy for mild persistent asthma or as adjunctive therapy with ICS
theophylline (Elixophyllin ®): dosing
**narrow TI drug, with goal serum concentration of 5-15 mcg/mL (30 min after loading dose)
- Initial loading dose generally required
- Time to peak serum concentration 1-2 h for PO, within 30 min for IV
METHYLXANTHINE
theophylline (Elixophyllin ®): Dosage forms
ER tablet (Theo-Dur®), capsule (Theo-24®), oral solution, IV solution
METHYLXANTHINE
theophylline (Elixophyllin ®): MOA
- Bronchodilation*: non-selective phosphodiesterase (PDE) inhibitors –> ↑ cAMP and cGMP concentrations
- Anti-inflammatory*: activation of histone deacetylase –> ↓ proinflammatory gene expression
METHYLXANTHINE
Factors that ↓ theophylline clearance
cimetidine; macrolides; quinolones; systemic viral illness; zileuton; propranolol
METHYLXANTHINE
Factors that ↑ theophylline clearance:
*phenytoin; rifampin; carbamazepine; smoking; phenobarbital; high protein diet
METHYLXANTHINE
theophylline (Elixophyllin ®): ADRs
Dose-related adverse effects: tachycardia; H/A; hypotension; N/V; hematemesis; hyperglycemia; hyperkalemia; seizures
IMMUNOMODULATORS: agents
only omalizumab (Xolair ®)
omalizumab (Xolair ®): indications
alternative agent for patients with sensitivity to relevant allergens in severe persistent asthma
IMMUNOMODULATOR
omalizumab (Xolair ®): dosing and administration
solution for subcutaneous injection [$1000 per dose]; dosing based on pre-tx IgE levels and body weight; 150-300 mg Q4 weeks; must be adjusted if significant weight change
IMMUNOMODULATOR
omalizumab (Xolair ®): pathophysiology
IgG monoclonal antibody that inhibits IgE receptor binding on mast cells and basophils; long-term use shows ↓ exacerbations and corticosteroid use
IMMUNOMODULATOR
omalizumab (Xolair ®): ADRs
anaphylaxis reported in < 0.2% patients; injection site RXNs
IMMUNOMODULATOR
ORAL CORTICOSTEROIDS (OCSs): Indications
last resort!; short course (up to 2 weeks) indicated for pts. w/ poor asthma control; reduces sx duration, prevents hospitalizations and ↓ likelihood of relapse post-exacerbation
Metered Dose Inhalers (MDI): how to use
- Shake the inhaler well before use; remove cap
- Exhale away from inhaler
- Bring the inhaler to your mouth.
- Place it in your mouth between your teeth and close you mouth around it.
- Start to breathe in slowly.
- Press the top of you inhaler once and keep breathing in slowly until you have taken a full breath.
- Remove the inhaler from your mouth, and hold your breath for about 10 seconds, then breathe out.
Diskus (Dry powder inhaler): how to use
- Hold Diskus in palm of hand (sandwich)
- Push thumb grip until it clicks into place
- Slide lever away from you
- Place it in your mouth between your teeth and close you mouth around it.
- Start to breathe in deeply and rapidly.
- Remove the inhaler from your mouth, and hold your breath for about 10 seconds, then breathe out.
- Always check the number in the dose counter window to see how many doses are left
Twisthaler (Dry powder inhaler): how to use
- Twist white cap counter clockwise
- Exhale away from Twisthaler
- Hold horizontally
- Place it in your mouth between your teeth and close you mouth around it.
- Start to breathe in deeply and rapidly.
- Remove the inhaler from your mouth, and hold your breath for about 10 seconds, then breathe out.
- Replace cap and twist clockwise.
- Make sure it clicks to completely close it.
- Rinse mouth and gargle
Spacers: benefit
- Enhanced drug delivery, highly recommended with ICS for pediatrics
- Canister holds drug in place. Can inhale at own pace – good for pedi who may not have high lung capacity
Asthma: Step-Up Pharmacotherapy for Well Controlled
Well controlled
- Frequent follow up (1 – 6 month intervals)
Asthma: Step-Up Pharmacotherapy for Not well controlled
Step up 1 step and re-evaluate (2 – 6 weeks)
Asthma: Step-Up Pharmacotherapy for Poorly controlled
Step up 1 or 2 steps and re-evaluate
Consider short course of oral corticosteroids
How does pregnancy affect asthma?
- Worsens in one-third of pregnant females
Asthma and pregnancy: preferred rescue agent
Albuterol: Preferred rescue agent
Asthma and pregnancy: preferred maintenance agent
Budesonide: Preferred maintenance agent
Asthma and pregnancy: agents to avoid
Long-acting beta agonists
Omalizumab
Zileuton
