Asthma Treatment Flashcards
Characteristics of Asthma
- recurrent episodes of coughing, SOB, chest tightness, wheezing
- intensity can range from mild (exposure to allergens, exercise, URI) to severe (limiting)
- Reduce FEV1, FEV/FVC and peak expiratory flow rate
- TLC, FRC, and residual volume may be increased bc of airflow obstruction
- DLCO may be increased because of inc lung and capillary blood volume
Pharmacology of asthma
bronchodilation (reduce smooth muscle contraction) and inflammation (reduce edema and cellular infiltration)
-address hyperreactivity
innervation of lung
- afferent vagal pw travel to CNS
- efferent vagal pw to autonomic ganglia
- parasympathetic tone high, inc constriction and mucus release- post ganglionic fibers release ACh binding to muscarinic receptors on bronchial smooth muscles
Bronchodilation occurs via
- cAMP determines bronchial smooth muscle tone
- cAMP will lead to bronchodilation
- b2 adrenergic agonists increase cAMP synthesis by adenylyl cyclase
- phosphodiesterase inhibitors slow cAMP degradation
Bronchoconstriction inhibited by
Muscarinic receptor antagonists (dec parasympathetic tone)
Adenosine receptor antagonists (theophylline)
B2 adrenergic agonists
- albuterol, salmeterol, formoterol, terbutaline
- salmeterol and formoterol are more long acting
- stimulate adenylyl cyclase to inc cAMP
- acute asthmatic attacks
- minimal adverse cardiac effects for short acting
- long duration of action, dilation max at 30 min and lasts 3-4 hrs
- safe and effective
- common AE are skeletal muscle tremor, nervousness, weakness
Sympathomimetics
- epinephrine and ephedrine
- Cardiac adverse effects- tachycardia, arryhthmia, worsening of angina due to stimulation of beta1 adrenergic receptors
- epinephrine is inhaled or injected subq, effective and acts rapidly in acute attacks
Methylxanthines
- aminophylline, theophylline, dyphylline, pentoxifylline, caffeine, chocolate
- oral sustained release or parenteral preparations
- broad effects, dirty side effects but its low cost so widely used
- PDE4 inhibition (inh degradation of cAMP)
- -> bronchodilation
- cardiac stimulation, vascular smooth muscle relaxation, tachycardia, reduced inflammatory cytokine release, oppose actions of adenosine
- CNS stimulation results in alertness, insomnia, tremors, convulsions; pos inotropic and chronotropic effects may produce arrhythmias and inc bp
- stimulate secretion of gastric acidand digestive enzymes (like coffee)
- weak diuretics due to inc GFR and diminished Na reabsorption, improved contractility of skeletal muscle and diaphragm
most effective methylxanthine
theophylline
-inexpensive, oral
muscarinic receptor antagonist
atropine, ipratroium, tiotropium
- block Ach binding at muscarinic receptors (parasympathetic tone increased at night)
- inh responses to vagal stimulation- relax bronchial smooth muscle and decrease mucus secretion w/o affecting responses to nonmuscarinic stimuli
- unpredictable efficacy because parasympathetic involvement can be highly variable (good for those whose attacks occur overnight)
- atropine is prototypic drug (IV or inhalation)
Atropine AE
- muscarinic receptor antagonist
- mouth drying, urinary retention, tachycardia, loss of visual accommodation, agitation
ipratropium bromide
-aerosol or nasal spray allows large dose delivery bc poorly absorbed and minimal CNS effects
tiotropium
muscarinic receptor antagonist, longer doa
Glucocorticoids
-beclamethasone, dexamethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone
-reduce production of inflammatory cytokines which reduces bronchial reactivity, increase airway caliber (reduced edema), reduce frequency of asthmatic attacks
-oral or parenteral delivery- severe adverse effects
-
AE of glucocorticoids systemic
-weight gain, acne, hypokalemia, htn, osteoporosis, glaucoma, muscle wasting
