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DEFINITION OF ASTHMA:
Chronic, inflammatory, obstructive disease of the airways.
WHAT IS THE CORNERSTONE OF SYMPTOM CONTROL?
Identification of triggers and chronic management.
ARE THE SYMPTOMS PREVENTABLE AND REVERSIBLE?
- -6 PER 100 PEOPLE IN U.S. (4.8 MILL KIDS)
- -500,000 HOSPITILIZED PER YEAR
- -5,000 DEATHS PER YEAR
- -80% have ALLERGIES!
- -Childhood onset strongly related to atopy (genetic predisposition)
- -Adult onset: co-existing sinusitus, environmental exposure
PATHO OF ASTHMA- "THE VICIOUS CYCLE"
- 1. Inflammation- Stimuli by offending agent
- 2. Obstruction- Increased resistance to airlow-the major issue in Asthma.
- 3. Hyper-responsiveness- Now we are in trouble!
- A. Airway edema
- B. Mucous production and secretion
- C. Release of Histamines, Leukotrienes, Eosinophils, Cytokines that all contribute to inflammation of the airway and edema and desquamation (peeling) of the bronchial tissue.
- #3 just keeps happening because it is hard to treat at this point.
GOALS OF TREATMENT-
- 1. Minimal or no symtoms
- 2. Minimal episodes of exacerbation
- 3. No ER visits
- 4. Minimal need for rescue treatment
- 5. No limit on activities or exercise
- 6. Reduce morbitity (good control so there is no cellular remodeling).
- 7. Reduce mortality.
- Step 4: Severe Persistent- s/s severe, exacerbations several X's a day- Unable to perform any ADL's
- Step 3: Moderate Persistent- have s/s q day, impact quality of life- limit ADL's.
- Step 2: Mild Persistent- s/s mild but occur more often than 2 x's week.
- Step 1: Mild Intermittent- s/s mild, less than 2x's a week.
MEDICATION USED IN THE TREATMENT OF ASTHMA-
- 1. Inhaled steroids
- 2. Mast cell stabilizers
- 3. Leukotrience modifiers
- 4. Beta 2-Adrenergic agonists
- 5. Combinationlong-acting Beta 2 and inhaled steroid
- 6. Systemic corticosteroids
1ST LINE THERAPY:
- 1. Inhaled Steroids-
- Keep the triggers from activating from stimuli.
- -Must treat the inflammatory process by suppressing it to prevent the stimuli of the cycle...early on.
- -Decreases hyper-responsiveness from happening
- -Provide long term symptom suppression
- -USED ONLY FOR CHRONIC ASTHMA- DO NOT WORK FAST ENOUGH FOR ACUTE.
MOA OF INHALED STEROIDS:
-MOA- quickly enters target cells/reduce the number of circulating Eosinophils and Mast cells- like a protective coating tokeep allergens from breaking through.
DOSAGE OF INHALED STEROIDS:
Dosage: lowest dose to achieve control- 2-4 puffs bid-
PROTOTYPES OF INHALED STEROIDS:
- 1. Pulmicort
- 2. Vanceril
- 3. Azmacort
S/E OF INHALED STEROIDS:
- 1. Oral/esophageal candidasis
- 2. Dysphonia (voice impairment)
- 3. Hoarseness
- 4. cough
MAST CELL STABILIZERS ARE THE 1ST LINE IN?
MAST CELL STABILIZERS-
-Not immediate relief- non effective on bronchospasm. Only chronic treatment.
MOA OF MAST CELL STABILIZERS:
- -Inhibit the release of mediators from mast cells
- -Suppress the influx of inflammatory cells
PROTOTYPE OF MAST CELL STABILIZERS:
S/E OF MAST CELL STABILIZERS:
- 1. H/A
- 2. Nasal irritation
- 3. Unpleasant taste
- 4. Dry throat.
INDICATION FOR LEUKOTRIENE MODIFIERS?
Chronic management, NOT IMMEDIATE, NOT FOR ACUTE BRONCHOSPASM
MOA OF LEUKOTRIENE MODIFIERS:
- -Blocks leukotrience receptors resulting in reversal of bronchoconstriction and inflammatory cell infiltration.
- -Decreases the potent inflammatory mediators which are increased in Asthma.
PROTOTYPE OF LEUKOTRIENE MODIFIERS:
INDICATION FOR METHYLXANTHINES:
Adjunctive therapy in ACUTE and CHRONIC management.
MOA OF METHYLXANTHINES:
Prevents breakdown of (c-AMP) cyclic adenosine monophosphate by inhibiting PDE (phospodiesterase isoenzyme) which relaxes smooth bronchial muscles.
METHYLXANTHINES HELP TO?
- -Reduce the number of Eosinophils, lymphocytes, and monocytes.
- -They are well absorbed by the gut (po), widely distributed, and able to cross the blood-brain barrier to enter the CNS.
- -Is variable
- -8 hours in non-smoker adult and children
- -4.5 hours in adults who SMOKE
WHAT DOES CIGARETTE SMOKE DO WITH METHYLXANTHINES?
Cigarette smoke contains compounds which incuse CYP1A2 (same pathway which methylxanthines are metabolized) smokers metabolize methylxanthines FASTER and require HIGHER dosages to maintain theapeutic levels.
METHYLXANTHINES THERAPEUTIC LEVEL:
- -5-15 mg/L, VERY DIFFICULT to control due to multiple D/D interactions.
- -D/D interactions: ASA, Erythromycins, and Coumadin
- 1. Theophylline
- 2. Amathphylline
S/E OF METHYLXANTHINES-
- 1. h/a
- 2. dizziness
- 3. GI upset
- 4. Myalgia (muscle pain)
ARE BETA 2 ADRENERGIC AGONIST USED FOR ACUTE OR CHRONIC ASTHMA?
FOR ACUTE BRONCHOSPASMS!!!!!
MOA OF BETA 2 ADRENERGIC AGONIST-
- -THEY ARE BRONCHODILATORS
- -Most effective tx for acute bronchospasm
- -Immediate relief
- -Acts on Beta 2 adrenergic receptors ONLY to relax smooth muscle- THERE IS NO ANTI-INFLAMMATORY EFFECT! (so need something else too).
DOSAGE OF BETA 2 ADRENERGIC AGONIST:
PO or inhalation (preferred), 2 puffs q 4-6 hrs (short-acting)
PROTOYPES OF BETA 2 ADRENERGIC AGONISTS:
- 1. Albuterol (short acting 4-6 x day)
- 2. Ventolin (short acting)
- 3. Proventil (short acting)
- 4. Serevent (long acting q 12 hrs)
S/E OF BETA 2 ADRENERGIC AGONISTS:
- 1. Tachycardia
- 2. Plapations
- 3. Tremors
- 4. Anxiety
- ALL OVERUSE/DOSE RELATED!
SPECIAL CONSIDERATIONS FOR USE OF BETA 2 ADRENERGIC AGONISTS:
- 1. Not used in kids less than 6 yrs old
- 2. No use in pregnancy/lactation
- 3. Dangerous to overuse (pt. education)
MOA OF COMBINATION LONG-ACTING BETA 2 AND INHALED STEROID OCMBINED (ADVAIR DISKUS):
Combines the benefits of anti-inflammatory (steroid) and relaxtion of bronchospasm (Beta-2).
DOSAGE OF COMBINATION LONG ACTING BETA 2 AND INHALED STEROID:
Inhalation via device bid (Advair diskus)
PROTOTYPE OF COMBO LONG ACTING BETA2 AND INHALED STEROID?
1. Advair diskus
S/E OF LONG ACTING BETA 2 AND INHALED STEROIDS?
1. Oral candidiasis
INDICATIONS FOR SYSTEMIC CORTICOSTEROIDS?
- 1. Treatment of ACUTE exacerbations
- 2. Maintenance therapy: low dose
MOA OF SYSTEMIC CORTICOSTEROIDS:
- -Inhibits cytokine and mediator release
- -Suppress inflammatory cell influx of inflammatory agents.
DOSAGE OF SYSTEMIC CORTICOSTEROIDS:
- -Readily absorbed
- -Symptom relief with 24 hours
- -Initally: 30-60 mg zd, TAPER OFF over 5-14 days
- -SHORT TERM USE: administer at 3 pm because it mimics body's natural cortisol level.
- -LONG TERM USE: administer in AM, lowest possible dose, consider qod adm (less adrenal suppression so that body doesn't lose its natural response)
PROTOTYPE OF SYSTEMIC CORTICOSTEROIDS:
- 1. Methylprednisolone (Medrol dose pack)
- 2. Prednisone
- 3. Deltasone
S/E OF SYSTEMIC CORTICOSTEROIDS:
- 1. Psychosis
- 2. Sleep disorders
- 3. N/V
- 4. Peptic ulcers
- 5. Mood swings
- 6. Hyperglycemia
PHARMACOLOGIC TREATMENT OF ASTHMA:
- 1. Multi-factorial causation requires multi-factorial treatemnt
- 2. Prevention of trigger is MAINSTAY of effective long term management
- 3. Chronic treatment of Inflammatory Process with INHALED CORTICOSTEROIDS
- 4. Provide Beta 2 adrenergic agonist routinely and PRN rescue
- 5. Patient education.