Pulm Pharm Flashcards
Drug deposition of inhaled drugs: ideal size
1-5 micrometers= ideal for smaller airways
> 10 micrometers= deposited in lung, oropharynx
< 0.5 micrometers= inhaled and exhaled without deposition
Quick relief drugs (asthma)
Take when you have symptoms:
- Short acting bronchodilators
- High dose oral or IV medications
Controller (asthma)
Controller= take every day
- anti-inflammatory
- mediator antagonists
- longer-acting bronchodilators
MOA of Beta-2 agonists
Binds receptor–> increased adenylyl cyclase–> increased cAMP–> PKA–> decreased Ca+2–> bronchorelaxation
Selective Beta-2 agonists
Clinical role:
- Acute symptom relief: Bronchorelaxation, Minimal tachyphylaxis
- Bronchoprotection: Known triggers (cold air, allergens), Attenuates with repeated use
- No antiinflammatory properties
- Oral administration should be avoided
Short acting: Albuterol= workhorse drug
- First choice quick relief for asthma
- As needed ~every 4 hours
- Higher doses used in acute attack
Long acting: salmeterol, formoterol
- Every 12 hours
- Theoretical concerns of tachyphylaxis; NOT for immediate relief
- Should NOT be administered without inhaled steroids
AEs: tachycardia, tremor, nervousness
- hypokalemia: CV disease with diuretic use= highest risk–> potential arrhythmia (COPD population)
Albuterol
Workhorse drug for asthma (short-acting) Beta-2 agonist - First choice quick relief for asthma - As needed ~every 4 hours - Higher doses used in acute attack
Salmeterol/formoterol
Long-acting asthma drug- beta-2 agonist
- Every 12 hours
- Theoretical concerns of tachyphylaxis; NOT for immediate relief
- Should not be administered without inhaled steroids
Corticosteroid use in asthma
MOA: Bind cytoplasmic receptor associated with HSP 70 & 90 and immunophilin (target of cyclosporine)
- Translocation to nucleus to serve as transcription factor
- Widespread cellular effects
Effects:
- decrease lymphocyte number
- decrease cytokine release and production by lymphocytes and macrophages
- decrease endothelial cell adhesion molecules (ICAM-1)
- Eosinophil apoptosis
- decrease prostaglandin and leukotriene C4
- decrease fibroblast proliferation
AEs: immunosuppresion, gastric ulcers, osteoporosis, muscle wasting, cataracts (blocking immune response)
Inhaled corticosteroids for asthma/COPD
Long term administration: Mainstay of asthma treatment
- Use in ALL except mildest disease
- No immediate bronchorelaxation
COPD usage: decreases exacerbations but does not change mortality/lung function
Side effects mild and dose related:
- HPA suppression–minimal
- Cataracts–posterior subcapsular
- Growth velocity in children: Titrate dose to control of disease
- Bone mineral density: significant decrease only at higher doses
- Fractures: no increased risk, but poor data
- Pneumonia—mild risk in COPD patients
Local side effects:
- Dysphonia, thrush: independent of type of steroid
- Strategies to avoid: rinse mouth, spacer device
Treatment side effects typically better than severe disease in children
Parenteral (IV or IM) corticosteroids for asthma
- Used in severe attacks
Oral corticosteroids for asthma
Used in acute exacerbations: excellent bioavailability
- Long term use for asthma and COPD associated with significant toxicity
- Short term use very effective
- Preferred to increasing dose of inhaled steroid
- Initiate therapy early in exacerbation
- Use appropriate dose, usually for ~ 5-10 days
- Monitor for decline in symptoms
Anticholinergics for asthma: MOA
CNS, autonomic ganglia, heart, GI system, sweat glands, GU tract, eye
- 5 receptor subtypes
Lung receptors:
- M3 receptor: smooth muscle and mucous glands
- Antagonism of receptor inhibits bronchoconstriction by histamine, bradykinin, eicosanoids and decreases production of secretions (anesthesia)
- Jimson weed (atropine) smoked in India to treat asthma
Pharmacokinetics/pharmacodynamics of anticholinergics
- Only 1% of inhaled dose absorbed
- MDI or nebulization
- Scheduled (not symptom driven) dosing
Ipratropium (Atrovent)
- Maximal response 30-90 min, duration 4-6 hr
Tiotropium (Spiriva)
- Slower onset, duration of action 24 hours
- M1 and M3 selective
Clinical use of inhaled anticholinergics
- Effect depends upon vagal tone
- Minimal effect on mucociliary clearance
- First line therapy in COPD (after smoking cessation)
- Adjunct in asthma
- Side effects mild: Dry mouth
Leukotrienes in asthma
Eicosanoid family: increase or attenuate inflammation
- C4, D4= mediators of inflammation
- Derived from arachidonic acid
- Basis for aspirin-sensitive asthma: aspirin shunts arachidonic acid into leukotriene pathway
- Bind to CysLT receptor–> effector reaction
In Asthma: Potent effectors of airway obstruction; Leukotrienes cause:
- Bronchial constriction
- Vasodilation
- Leukocyte chemotaxis
- Edema
Leukotriene drugs in asthma= receptor antagonists or synthesis inhibitors
Montelukast
Leukotriene receptor antagonist (modifiers)
- q day; Very safe
- Add-on controller agent in asthma
- Pediatrics: oral, steroid sparing
- Treats allergic rhinitis
- Heterogenous response
- NO ROLE in COPD
Side effects:
- Churg-Strauss vasculitis (associated with severe asthma, responds to corticosteroids)
Zafirlukast
Leukotriene receptor antagonist (modifiers)
- BID; Mild Cytochrome P450 inhibition
- Very safe
- Add-on controller agent in asthma
- Pediatrics: oral, steroid sparing
- Heterogenous response
- NO ROLE in COPD
Side effects:
- Churg-Strauss vasculitis (associated with severe asthma, responds to corticosteroids)