Asthma Pharmacology Flashcards
Chronic Asthma
- Tx based on (1) disease severity and (2) level of control for subsequent therapies
- Personalized care plans
- Avoidance of triggers
- As needed for quick relief medications
- Short acting beta agonists (SABA)
- Anticholinergics
- Systemic corticosteroids
- Long term control medications
- Inhaled corticosteroids
- Inhaled LABA
- Leukotriene modifiers
- Theophylline
- Omalizumab
Acute Severe Asthma
- Written action plan
- Recognition of early indicators of acute exacerbation
- Appropriate intensification of therapy
- Removal of triggers or irritants
- Timely communication b/t pt and clinician
Tx options: oxygen, SABA +/- ipratopium bromide (anticholinergic), systemic corticosteroid, close monitoring
Bronchodilators
Reverse the bronchospasm of the immediate asthmatic response
- B2-Adrenergic Agonists
- Anticholinergics
- Methylxanthines
Bronchi Anti-inflammatory Agents
Inhibit the inflammatory components of the immediate and late asthmatic responses
- Corticosteroids
- Leukotriene modifiers
- Mast cell inhibitors
- Anti-IgE antibody
B2-Adrenergic Agonists
- Relax airway smooth muscle by stimulating B2-adrenergic receptors
- Increase cAMP –> bronchodilation
- Decrease cAMP –> bronchoconstriction
- Increase mucociliary clearance
- Stabilize mast cell membranes & inhibit inflammatory cells
Adverse effects: (worse / PO vs. inhaled)
- Tachycardia
- Tremor
- Hypokalemia
Short-Acting Inhaled B2-Agonists (SABA)
- Drug of choice for quick relief asthma symptoms (severe and chronic) and prevention of exercise-induced bronchospasm
- Onset of action < 5 min (metered-dose inhaler + spacer is quicker & as effective as NEB)
- Duration of action 4-6 hours
- Albuterol (racemic mixture)
- Levalbuterol (R-enantiomer)
- -much more expensive!
Doses: 2 puffs every 4-6 hours PRN, 2 puffs 5 minutes before exercise, doubled dose for exacerbations
*Regular use of inhaled SABAs is not recommended & indicates need for additional long-term control therapy
Asthma Control Therapy
Inhaled corticosteroids:
- More effective controllers for asthma, anti-inflammatory effects
- Used in treating asthma of any severity at any age
- Usually taken twice daily
Systemic steroids:
- Used in acute asthma via IV or PO
- Small % of asthma pt’s require this
Leukotrienes
Leukotrienes = inflammatory mediators produced by mast cells that cause bronchoconstriction A
Cromones
Inhibit mast cells and sensory nerve activation
- Effective in blocking trigger-induced asthma (early and late-phase responses)
- Short duration of action–less effective for long-term control (cromolyn nebulizer)
- Alternative to inhaled corticosteroids in mild persistent asthma*
- 3-4 times/day
- Well tolerated
- Improvement in 1-2 weeks, max benefit in 4-6 weeks
Goals of Chronic Asthma Therapy
- Reduce/eliminate chronic symptoms
- Eliminate exacerbations/ED visits
- Reduce side effects of medications
- Reduce the need for B-agonists
- Eliminate activity restrictions
*Children follow a personalized asthma action plan (begin w/ B2-agonists and add on if needed)
Goals of Acute Asthma Attack Therapy
- Reverse obstruction very rapidly
- Intubate if needed
- Administer medications as dictated by the pt
Tx of Acute Asthma Attack
Tx is that same for adults and children, except for doses
1st: B2-agonist (i.e., albuterol), NEB or IM
* Combine with anticholinergics (DUONEB) to increase efficacy, continuous x 1 hour
* +/- Magnesium IV x 30 min
2nd: Epinephrine or Terbutaline, SQ if NEB intolerant
Other:
- Corticosteroids, PO, reduce hospitalization time
- Heliox: Inhaled mix of helium and oxygen
- Oxygen between NEB treatments (O2 saturation at least 90%)
- Intubation w/ severe respiratory compromise, exhaustion, change in mental status, or acidosis
Long-Acting Inhaled B2-Agonists (LABA)
- Add on therapy* for asthma poorly controlled with low-medium doses of ICS
- Benefits: as effective as doubling dose of ICS, & reduces side effects of ICS
- Duration of action up to 12 hours
NOTE: Never use as monotherapy for chronic asthma
- Increased risk of severe asthma exacerbations & related deaths (black box warning)
- Use only with long-term control medication
- Discontinue when pt’s asthma is controlled
LABA Drugs
Salmeterol (Serevent)
- Partial agonist
- Onset of action of ~30 minutes (not quick relief)
- Caution pt’s not to use as a rescue tx
Formoterol (Foradil)
- Full agonist
- Onset of action < 5 minutes
- Not approved for treatment of acute bronchospasm
LABA Drug Combinations
- Specifically designed for pediatrics*
- Ensure the pt is not taking a LABA without a control medication
Advair: Fluticasone and salmeterol
Symbicort: Budesonide and formoterol
Corticosteroids
- 1st line for asthma tx, along with B2-agonists*
- Decrease airway inflammation
- Decrease hyper-responsiveness
- Decrease mucus production and secretion
- Improve response to B2-agonists (d/t a decrease in inflammation)
Inhaled Corticosteroids
Preferred therapy for persistent asthma
(any severity, any age, 2x daily)
- Targeted drug delivery to the lungs decreases the risk of systemic effects
- Onset of action within 12 hours (not for quick relief, pt should be taking this daily)
- Significant clinical effects apparent after 2+ weeks
Adverse Effects:
- Local–Oral candidiasis, cough, hoarseness, dysphonia (reduce by using spacer & rinsing mouth after use)
- Systemic–adrenal suppression, decreased bone mineral density, skin thinning, cataracts, easy bruising, growth suppression in children (dose dependent)
Indications for Systemic Corticosteroids
Long-term control:
- Only if other therapies fail
- Administer 1 daily or every-other-day
- Frequently attempt to decrease/discontinue
Asthma exacerbation:
- Effective for worsening asthma not responding to bronchodilators & for acute severe asthma
- Short course or “bursts”
Acute severe asthma
- Hasten recovery, decrease hospital admission (if given w/in 1 hour), reduce relapse rates
- Onset of effect between 4-12 hours
- PO is preferred over IV
- Duration of tx between 3-10 days (no tapering)
Systemic Corticosteroid Drugs
Prednisone, Methylprednisone, Prednisolone
*Used in acute asthma* Usual adult dose: IV or PO - Long term-every other day - Acute, severe-1 or 2 doses - Exacerbation-1 or 2 doses x 5-10 days
Anticholinergics
- 2nd line or add on therapy to B2-agonists*
- MOA: Inhibit the effects of acetylcholine on muscarinic receptors in the airways
- Adverse effects: Blurred vision, dry mouth, urinary retention, constipation
Anticholinergic Drugs
Ipratropium (Atrovent)
- Onset of action ~30 minutes
- Duration of action of 4-8 hours
*Add to B2-agonists in acute severe asthma to improve pulmonary functioning & decrease hospitalization rates (no evidence for long-term control therapy)
Leukotriene Modifiers
Zileuton
- Inhibits 5-lipoxygenase
Montelukast, Zafirlukast
- Competitiely antagonize the effects of leukotriene D4
- Improve FEV1 and decrease asthma sxs, frequency of rescue inhaler use and exacerbations
- Less effective than ICS, can use as combination therapy
Montelukast (Singulair)
Leukotriene modifier of choice
Dosing: once daily at bedtime
No significant increase in hepatic enzymes (AST, ALT) and NO EFFECT on cytochrome P450 enzymes
Zafirlukast (Accolate)
Leukotriene Modifier
- Dosing: BID at least 1 hour before or 2 hours after meals
- Causes an adverse increase in hepatic enzymes (do NOT need to monitor)
- Inhibits some cytochrome P450 enzymes (CYP 2C9, CYP 3A4)–drug interactions
Zileuton (extended-release tablet, Zyflo CR)
Leukotriene Modifier
- Dosing: BID, within 1 hour after morning and evening meals
- Causes an adverse increase in hepatic enzymes (must check liver enzymes at baseline, monthly for the first 3 months, every 2-3 months for the 1st year, then periodically)
- Inhibits one cytochrome P450 enzyme (CYP 1A2)–drug interactions
Methylxanthines
Theophylline
MOA: Bronchodilation by inhibiting phosphodiesterase and antagonizing adenosine
- Limited use d/t inferior efficacy compared to ICS, narrow therapeutic index, potentially life-threatening toxicity, & clinically important drug interactions
Adverse Effects: (< 20 mg/dL) = HA, N/V, insomnia, gastric upset & irritability, (> 20 mg/dL) = cardiac arrhythmias, seizures, toxic encephalopathy, & death
Theophylline
Methylxanthine
[5-15 mg/L], dose: 10-300 mg
Drug Interactions:Metabolized by P450 enzymes
- Levels increase w/ Cimetidine, Erythromycin, Clarithromycin, Propanolol, Cyprofloxacin
- Levels decrease with smoking & anti-convulsants (Carbamazepine, Phenytoin)
Anti-IgE Antibody Drugs
Omalizumab
- Recombinant humanized monoclonal anti-IgE antibody
MOA: Inhibits binding of IgE to receptors on mast cells & basophils, resulting in inhibition of mediator release
Indications: Moderate to severe persistent asthma, 12 years of age or older, not controlled by ICS, + skin test or in vitro reactivity to perennial allergens
CI: Use is limited by high cost
Omalizumab
Anti-IgE Antibody Drug
Benefits: Decreases ICS use, reduces # and length of exacerbations, increases asthma-related QOL
Adverse Effects:
- Injection site reactions (bruising, redness, pain, stinging, itching, burning)
- (Rarely) Anaphylactic reactions (bronchospasm, hypotension, syncope, urticaria, angioedema)–any dose, up to 2 hours after administration
- Malignancy
Dosing: SQ every 2-4 weeks, based on weight and initial IgE serum concentration
Tx of Intermittent Asthma
- Long-term control medications not needed*
- SABA for prevention or tx
- 2 puffs of albuterol prior to exposure of known trigger
- Monitor for heavy use, if > 2x/wk, switch to long term medication
Tx of Persistent Asthma
- Daily long-term control therapy required (drug of choice = ICS)
- SABA as needed
Follow-up:
- Within 2-6 wks after initiating or increasing therapy
- Every 1-6 months once controlled
Tx of Severe Acute Asthma
- Early & appropriate intensification of therapy is imperative to resolve the exacerbation, prevent relapse, & prevent severe airflow obstruction in the future
- Therapy should be started at home based on written action plan
Tx of Asthma: Children Ages 0-4
Initiate long-term control meds if:
- 4+ episodes of wheezing within last year that lasted for > 1 day & affected sleep
- Pt w/ 1 major or 2 minor risk factors for developing persistent asthma
Consider long-term control meds if:
- Require symptomatic tx > 2 days/wk for > 4 weeks
- 2 exacerbations requiring systemic steroids within 6 months
Tx of Asthma During Pregnancy
- ~1/3 of pregnant women w/ asthma experience worsening asthma during pregnancy
- Safer to treat w/ medications than have uncontrolled asthma
- Budesonide*–1st line ICS
- Albuterol*–1st line for sxs & exacerbations
Exercise-Induced Asthma
- SOB, wheezing, or chest tightness during or shortly after vigorous exercise
- Peak 5-10 minutes after stopping activity
- Resolve within 20-30 minutes
- Exercise challenge can confirm diagnosis*
- > or equal to 15% decrease in PEF or FEV1 post-exercise
Tx of Exercise-Induced Asthma
- Warm up prior to vigorous exercise
- Cover mouth & nose w/ scarf or mask during cold weather
- Cool down prior to stopping
- Pretreat w/ albuterol 5 minutes prior
- Albuterol alternatives: Cromolyn, Leukotriene modifier, daily tx w/ ICS
DuoNEB
- Combination of Albuterol & Ipratropium*
- Can and should be used multiple times in acute asthma attacks
- Advised that children receive DuoNEB continuously for up to 1 hour during an acute attack
Magnesium
- Used for acute, severe attacks
- Bronchodilator
- Typically used in conjunction after other therapies have been initiated (e.g B2-agonists)
- Given over 30 minutes
Heliox
- Mixture of helium & oxygen
- Can lower airway resistance
- Adjunct to other therapies in severe exacerbation
Oxygen
Given to all pts between NEB treatments to maintain O2 saturation of at least 90%
Indications for Intubation
- Severe respiratory compromise
- Exhaustion
- Change in mental status
- Acidosis
