Pharmacotherapy of _____Asthma______

Sareh Seyedkazemi, PharmD Candidate 2007

Epidemiology / Asthma affects 5% of the US population (epidemic).
-~33% (5 million) are children <5 years old most common chronic disease among children.
-1.6% of ambulatory care visits, 470,000 hospitalizations, & 2 million ER visits/year.
-Highest prevalence among children  68.6 per 1000 population younger than 18 years.
Effects on Productivity
-3rd leading cause of preventable hospitalizations in the US
-prevalence of disabling asthma in children: ↑ 232%
Ethnic Differences
-Prevalence, Hospitalizations, & ER visits: African Americans and Hispanics > Caucasians
Cost Burden (Direct and Indirect)
-$14 billion cost impact in 2000.
-$9.4 billion in direct costs.
Outcomes:
-prevalence and morbidity are increasing
-mortality leveled off at 5000 deaths/year may be declining.
DiseaseState Definition / -According to the NHLBI guidelines, Asthma is defined as a “chronic disorder of the airways characterized by:
  • inflammatory component- cells such as mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells act together to create an inflammatory response
  • bronchial hyper-responsiveness- inflammation causes an associated increase in the existing hyper-responsiveness of the bronchials to various stimuli
  • reversible component- either spontaneously or with treatment

Patho-physiology / Early Phase Reaction:
  • Inhaled allergen activate cells bearing IgE  early phase reaction proinflammatory mediator production (histamine, eicosanoids, & reactive oxygen species) contraction of the airway smooth muscle, mucous production, and microvasculature vasodilatation.
** microvasculature vasodilatation plasma protein leakageedematous airway wall narrowing of the airway lumen
Late Phase Reaction: (6-9 hours after)
  • Mast cell proinflammatory cytokine production recruitment & activation of eosinophils, CD4+ T-cells, basophils, neutrophils, and macrophages
**Activation of T-cells  release of T-helper cell type 2-like cytokines (key mechanism of late phase response)
** Enhancement of non-specific bronchial hyper-responsiveness (BHR) may follow late response, but not early phase reaction.
Chronic Inflammation
Epithelial Damage (activation & shedding):
-decrease in the bodies natural defense and regulatory mechanisms
-heightened airway responsiveness
-altered permeability of airway mucosa
-depletion of epithelial-derived relaxant factors
-loss of enzymes responsible for degrading proinflammatory factors
Eosinophil activation leading to airway tissue damage
Lymphocytes
  • Increased production of CD4+ T-helper cells type 2 responsible for inflammatory reactioninhibits production of TH1 type cells which are essential for cellular defense mechanisms.
Mast cell degranulation contributing to disease progression
Inflammatory Mediators:
  • histamine
  • arachidonic acid and its metabolites (prostaglandins, leukotrienes, & platelet activating factor): may lead to airway bronchoconstriction.
  • Thromboxane A2: bronchoconstriction, involvement in late response and airway inflammation and BHR.
  • 5-lipoxygenase pathway of arachidonic acid metabolism production of leukotrienes- bronchospasm, mucous secretion, microvascular permeability, and airway edema.
Adhesion Molecules
  • necessary for migration of inflammatory components, activation of cells, and cell-to-cell communications
Airway Remodeling- replacement of injured tissue, secondary to inflammatory response, with parenchymal cells of the same type may lead to fibrosis, increase in smooth muscle, and mucous gland mass.
Neuronal Control
  • parasympathetic innervations bronchocontstriction (mainly in the bronchi and absent in small bronchioles.)

Clinical Presentation / Severe Acute Asthma
Symptoms:
  • anxious, respiratory distress, shortness of breath, chest tightness or burning, difficulty speaking, and unresponsiveness to inhaled B2 agonists.
  • Can progress over days to hours or rapidly over 1-2 hours.
Chronic Ambulatory Asthma
Symptoms:
  • may not have any symptoms at the time of presentation if not experiencing exacerbation.
  • Episodes of dyspnea, chest tightness, coughing (especially at night), or wheezing
  • May be spontaneous, in association with exercise, or secondary to allergens.
  • Responsive to inhaled B2 agonists

Risk Factors /
  • Genetic predisposition
  • Environmental-
  • Socioeconomic status/ Family size
  • Exposure to second hand tobacco smoke in infancy and in utero
  • Allergen exposure- i.e aeroallergens
  • Urbanization
  • Decreased exposure to common childhood infectious agents
  • Hygiene hypothesis: childhood development of allergic immunologic system rather than immunologic system that fights off infections (TH1)
  • Viral respiratory tract infections- most significant precipitant of severe asthma
  • Emotions- anxiety, stress, laughter
  • Exercise- in cold dry environment
  • Medications- ASA, NSAIDS, sulfites, benzalkonium chloride, beta blockers.
  • Occupational stimuli
  • Sinusitis and rhinitis
  • GERD-regurgitation causes a vagally-mediated reflex bronchoconstriction.

Diagnosis / Establishing correct diagnosis of Asthma requires:
  • presence of episodic symptoms of airway obstruction- (i.e cyanosis, change in nail bed color, classic symptoms of asthma)
  • obstruction at least partially reversible- FEV1↑ >12% with short-acting beta-agonists.
  • alternative diagnoses are excluded
Chronic Ambulatory Asthma:
  • FEV1/FVC <80%
  • 12% improvement in reversibility
Severe Acute Asthma:
  • PEF and/or FEV1 < 50% of normal predicted values
  • Decreased 02 Saturation < 90%

Desired Therapeutic Outcomes*
*Reference of
Guidelines Used / As per the National Asthma Education and Prevention Program Clinical Practice Guidelines for the Diagnosis and Management of Asthma, therapeutic goals include:
  1. Minimal or no chronic symptoms day or night
  2. Minimal or no exacerbations
  3. No limitations on activities; no school/work missed
  4. Maintain (near) normal pulmonary function (adults and children >5 years old only).
  5. Minimal use of short-acting inhaled beta2-agonists
  6. Minimal or no adverse effects from medications
*NAEPP Expert Panel Report Guidelines for the Diagnosis and Management of Asthma- Update on Selected Topics 2002
Treatment Options**
(Non-drug and Drug Therapy – include all therapeutic classes/agents available and preferences per treatment guidelines)
**See Treatment Options Table / **Please See Treatment Options Table
Severe Acute Asthma:
  • Β2- agonists
  • Corticosteroids
  • Anticholinergics
Chronic Asthma:
  • Corticosteroids
  • Long Acting β2 agonists
  • Methylxanthines
  • Cromolyn/ Nedocromil Sodium
  • Leukotriene Modifiers
  • Combination Controller Therapy
  • Anti- IgE

Monitoring
(Efficacy and Toxicity Parameters) / Efficacy:
[Subjective]: Pulmonary ROS- dyspnea, cough, chest tightness, wheezing, timing of symptoms, frequency of quick-relief medication use, PEFR, & c/o of interruption with ADLs
[Objective]: PE- cyanosis, hypoxia or fatigue, ability to complete sentences & ambulate, RR, use of accessory muscles. Pulse Oximetry- pO2. Spirometry- FEV1, FVC, FEV1/FVC.
Toxicity: Please refer to pharmacotherapy tables.

Sareh Seyedkazemi, PharmD Candidate 2007Pharmacotherapy Presentation – Pharmaceutical Care Rotation

University of MarylandSchool of PharmacyHappy Harry’s PharmacyPatientCareCenter, Perryville, MD