Asthma Flashcards
Receptors involved in asthma & result of stimulation
M3 in bronchial SM -> bronchoconstriction
B2 in airways -> bronchodilation
inflammatory mediators in asthma
Primary/early: histamine, protease, chemotactic factors (ECF, NCF)
Secondary/late: LKT B4, C4, D4, PGD2, cytokines
treatment strategies for asthma
manage inflammation with corticosteroids, mast cell stabilizers, LKT-R modulators
manage bronchoconstriction with B2-R agonists, anti-muscarinics, xanthine derivatives
MOA of beta-agonist
stimulate B2 stimulates AC = increased cAMP -> bronchodilation
MOA of theophylline
inhibits PDE = decreased cAMP breakdown = increased cAMP and bronchodilation
Also blocks adenosine to inhibit bronchoconstriction
MOA of muscarinic antagonist
block ACh to inhibit bronchoconstriction
Benefits of aerosolized asthma drugs
high local and low systemic concentration
fewer side effects
Benefit of spacer with aerosolized asthma drugs
improves ratio of inhaled to swallowed drug, no hand-mouth coordination needed
Fluticasone
glucocorticoid for asthma
potency of 1 (most potent)
MOA glucocorticoids
Decreased inflammation by modulating cyto/chemokine production, inhibiting eicosanoid synth, inh accumulation mast cells, decrease vascular permeability
Does NOT relax bronchial SM
Mometasone
GC for asthma
potency = 1 (most potent)
Beclomethasone
GC for asthma
potency = 0.5
budesonide
GC for asthma
potency = 0.5
flunisolide
GC for asthma
potency = 0.25 (least potent)
triamcinolone
GC for asthma
potency = 0.25 (least potent)
ciclesonide
GC for asthma
ADR of GCs for asthma
Dysphonia and oral candidiasis (prevent by gargling saline water)
Systemic GC effects w/ high dose
Growth retardation in children (will achieve normal adult height)
Types of b2-R agonists and timelines
Short-acting: max dilation in 15-30 minutes lasting 3-4 hours; for sx relief only
Long-acting: max dilation delayed, lasts 12+ hours; prophylaxis only; *usually combined with inhaled steroid & contraindicated for asthma if not used w/ steroid
Salbutamol
short-acting B2-agonist
albuterol
short-acting B2-agonist
terbutaline
short-acting B2-agonist
metaproterenol
short-acting B2-agonist
Salmeterol
long-acting B2-agonist
dry powder diskus
formeterol
long-acting B2-agonist
dry powder aerosolizer
also indicated for exercise-induced asthma
Corticosteroid + LABA combos
Advair: fluticasone + salmeterol
Symbicort: budesonide + formoterol
Dulera: mometasone + formoterol
ADR of B2-R agonist
fine tremors of finger/hand
palpitations
dizziness
restlessness/agitation
Use and MOA of muscarinic receptor antagonist
adjuvant therapy to B2-agonist and corticosteroids, also for allergic rhinitis
antagonizes M3-R and increases mucociliary clearance
Ipratropium, oxitropium, tiotropium
muscarinic receptor antagonists
Use and MOA of LKT modulators
Oral for mild-mod asthma prophylaxis, in combo w B-agonist and GC; also tx for allergic rhinitis
Antagonizes LKT actions to inhibit bronchoconstriction and decrease microvascular leakage and mucus production
inhibits influx of basophils and lymphocytes into airways
Types of LKT modulators
LKT-R blockers & LKT synthesis blockers
Montelukast
LKT-R blocker for asthma
Only drug approved for preventing exercise-induced asthma
Zafirlukast
LKT-R blocker for asthma
Zileuton
LKT synthesis inhibitor for asthma
inhibits LOX
ADR of LKT modulators
Minimal; may cause mild rise in liver enzyme levels
Use and MOA mast cell stabilizer
oral w poor bioavailability; used in asthma and allergic rhinitis as nasal spray
stabilizes mast cell from degranulation and inhibits release of inflammatory mediators from mast cell
*No effect on bronchodilation or SM relaxation
Sodium cromoglicate
mast cell stabilizer for asthma or allergic rhinitis
Nedocromil sodium
mast cell stabilizer for asthma or allergic rhinitis
Use and MOA of xanthine derivatives
bronchodilation and inhibition some aspects of late-phase asthma
inhibits PDE -> increase cAMP
inhibits cell surface receptors for adenosine
ADR of xanthines
CNS stimulant -> alertness, tremors, seizures
CVS stimulant -> increased HR, chronotropy (arrhythmia)
weak diuretic effect (increased GFR and dec tubular reabsorption)
Omalizumab
anti-IgE mab to inhibit binding to mast cell and degranulation
Other potential asthma drugs
anti-IL-4, IL-5, IL-13 mabs and antagonists of cell adhesion molcules
treatment of status asthmaticus
OACI: oxygen, continuous albuterol, systemic corticosteroids, intubation/ mechanical ventilation
B2-agonists, anti-ACh, GCs, bronchodilators (B2-ag > xanthine)
Why use anti-ACh in status asthmaticus
central suppression of conduction in vestibular cerebellar pathways
Why use GCs in status asthmaticus
decreased mucus production, improve oxygenation, reduct requirement for B2-agonist or theophylline, activate properties to prevent late bronchoconstriction
Use of magnesium sulfate in status asthmaticus
IV MS may relax SM -> bronchodilation and compete with Ca at Ca-mediated SM binding sites
Asthma drugs for pregnant women
Use same inhaled drugs because benefit»_space;> risk
Asthma drugs for children
Be mindful of excessive steroid use and hand-mouth coordination with MDIs