What are some precipitating/aggravating factors of asthma?
Viral Respiratory Infections Exercise Endocrine factors Drugs: Aspirin, Beta-blockers Weather changes: cold air Allergens Emotional expression: anger, laughing Food additives: Sulfites Environmental changes Exposure to irritants & occupational chemicals
What are some comorbid conditions of asthma?
Allergic/ Non-allergic Rhinitis Chronic sinusitis GERD Obesity Obstructive sleep apnea Other resp conditions Other allergic conditions Respiratory infections COPD Smoking nicotine dependence Hyperventilation Upper airway dysfunction Hormonal changes
Describe the components of asthma management.
Routine monitoring of Sx and lung function
Pt education to create partnership b/w clinician & Pt
Controlling environmental factors (trigger factors) & comorbid conditions that contribute to asthma severity
Pharmacologic therapy
What are the goals of asthma management?
1) Reduction in impairment
2) Reduction of risk
What are the 2 drug categories used for Asthma tx?
Anti-inflammatory drugs
Bronchodilators
Under Anti-inflammatory drugs, what are the subcategories?
Hormone-containing (corticosteroids)
- ICS
- Oral
Antibodies
Non-hormone-containing leukotriene receptor modifiers
- lipoxygenase inhibitors
- Receptor blockers
Under bronchodilators, what are the subcategories?
Beta-2 agonists (very effective)
- SABA (short-acting)
- LABA (long-acting)
Anti-cholinergic drugs
Methylxanthines
Describe the MOA of bronchodilator therapy. Include each subcategory of bronchodilators.
Beta agonists = stimulates AC increasing cAMP
Methylxanthine (theophylline):
- inhibits PDE increasing cAMP
- inhibits adenosine which causes bronchoconstriction
Muscarinic antagonists = inhibits Ach which causes bronchoconstriction
What drug category is most widely used in tx of Asthma and COPD?
B2 receptor agonists
What is the primary action of B2-agonists?
Relax airway smooth muscle cells of all airways
Name the B2-agonist drugs. Elaborate which are SABA vs. LABA.
SABA: Albuterol Terbutaline Metaproterenol Pirbuterol Levalbuterol
LABA: Fomoterol Salmeterol Indacaterol and Vilanterol Olodaterol
Describe the indications, adverse effects, & contraindications of Albuterol.
Indications = asthma, acute bronchitis, COPD, bronchiolitis
Adverse effects = HA, dizziness, insomnia, dry mouth, cough
Contraindications = Paradoxical bronchospasm, deterioration of Asthma, CV effects, immediate hypersensitivity rxns
Describe the indications, adverse effects, & contraindications of terbutaline. What is special about this drug?
Only B2 drug available by subcutaneous injection (not recommended for pts with sulfur allergy b/c it is a terbutaline sulfate injection)
Indications = Tx/prophylaxis of bronchospasm assoc with asthma, bronchitis, and emphysema in pts 12+
Adverse effects = HA, nausea, tachycardia, palpitation
Contra = Not recommended as medication for tocolysis (preterm labor)
Describe the indications & contraindications of Metaproterenol.
Indications = Bronchial asthma and for reversible bronchospasm which may occur in assoc with bronchitis and COPD
Contra = Produce signif cardiovascular effects in some pts. Can produce paradoxical bronchospasm
Describe the indications & contraindications of Pirbuterol.
Indications = Prevention and reversal of bronchospasm in pts 12+ with reversible bronchospasm including asthma. May be used with or without concurrent theophylline corticosteroid therapy
Contra = Cardiovascular effects
Describe the indications & contraindications of Levalbuterol.
Indications = Tx or prevention of bronchospasm in pts 4+ with reversible obstructive airway dz
Contra = Life-threatening paradoxical bronchospasm
Less CV effects than albuterol
Describe the indications and contraindications of Fomoterol.
Indications = Tx of ASTHMA in pt >5 YO as an ADD-ON to long-term asthma control medication such as inhaled corticosteroid
Maintenance Tx of bronchoconstriction in pts with COPD
Contra = In asthma, don’t use w/o concomitant use of long term asthma control meds such as inhaled corticosteroid.
Use of LABAs increases risk of asthma related death and hospitalizations
What do you absolutely need to remember about Fomoterol?
Prescribe for asthma ONLY as concomitant therapy with a long-term control med such as inhaled corticosteroid
Describe the indications of Salmeterol.
Tx of asthma in pts aged 4+
Prevention of EXERCISE-INDUCED bronchospasm in pts 4+
Maintenance Tx of bronchospasm assoc with COPD
Describe the indications of Indacaterol and Vilanterol.
Used to TX breathing probs caused by COPD, including chronic bronchitis and emphysema
Describe the indications of Olodaterol.
Used in long-term, once-daily maintenance bronchodilator tx of airflow obstruction in pts with COPD, including chronic bronchitis and emphysema
When should LABAs be used?
In concomitant use of a long term asthma control medication such as inhaled corticosteroid
What do you prescribe a pt with mild intermittent asthma?
Short-acting B2-agonist PRN
What do you prescribe a pt with mild persistent asthma?
SABA prn + ICS low dose
What do you prescribe a pt with moderate persistent asthma?
SABA prn + ICS low dose + LABA
What do you prescribe a pt with severe persistent asthma?
SABA prn + ICS high dose + LABA
What do you prescribe a pt with very severe persistent asthma?
SABA prn + ICS high dose + LABA + OCS
Name some combination inhalers (ICS + LABA).
Fluticasone + Salmeterol
Mometasone + Formoterol
Budesonide + Formoterol
What is the MOA of anticholinergic drugs (muscarinic antagonists)?
Block Ach form binding to receptors on certain nerve cells
Inhibit parasympathetic nerve impulses
What are the anticholinergic drugs most widely used in asthma/COPD?
Atropine
Ipratropium
Tiotropium
Aclindium
Describe the indications and contraindication of Atropine.
Indication = blockade of severe or life-threatening muscarinic effects
TEMPORARY BLOCKADE
Contra = when recurrent use of atropine in pts with CAD, the total dose should be restricted to 2-3 mg to avoid detrimental effects of atropine-induced tachycardia
Describe the indications of Ipratropium. Why can it be used for maintenance of tx unlike atropine?
Used as bronchodilator for maintenance tx of bronchospasm assoc with COPD, including chronic bronchitis and emphysema
Drug is potent atropine analog that is poorly absorbed after aerosol administration and is therefore relatively free of systemic atropine-like effects
Describe the indications of Tiotropium.
Indicated for long-term, once-daily, maintenance tx of bronchospasm assoc with COPD and for reducing COPD exacerbations
Describe the indications of Aclidinium.
Indicated for long-term maintenance tx of bronchospasm assoc with COPD, including chronic bronchitis and emphysema
Name some methylxanthines.
Theophylline (most widely used drug)
Theobromine (chocolate)
Caffeine
What are the 2 distinct actions theophylline has on the airways of pts with reversible obstruction?
1) Smooth muscle relaxation (bronchodilation)
2) Suppression of response of airways to stimuli (non-bronchodilator prophylactic effects)
In which pts do you have to be cautious of using theophylline?
Due to increased risk of exacerbation, use extreme caution in pts w/ active peptic ulcer dz, seizure disorders, & cardiac arrhythmias
What are the benefits of ICS therapy?
Most effective controllers of asthma
Most effective anti-inflammatory agents used in asthma therapy, reducing inflamm cell #s & their activation in airways
Reduce eosinophils in airways & sputum
Reduce #s of activate T-cells & surface mast cells in airway mucosa
What is the major effect of corticosteroids?
Switch off transcription of multiple activated genes that encode inflammatory proteins
How often are ICS prescribed?
Twice daily
Some may be effective once daily in mildly symptomatic pts.
ICS rapidly improves SX of? Effective in preventing asthma SX such as?
Rapidly improves SX of asthma, & lung function improves over several days
Effective in preventing asthma SX, such as exercise induced asthma and nocturnal exacerbations
Why is early treatment with ICS beneficial? What occurs with withdrawal of ICS?
Appears to prevent irreversible changes in airway functions that occurs with chronic asthma
Withdrawal of ICS results in slow deterioration of asthma control, indicating that they suppress inflammation and symptoms, but don’t cure underlying condition
Name some inhaled corticosteroids.
Beclomethasone Budesonide Ciclesonide Flunisolide Fluticasone Mometasone Triamcinolone
Name oral and parenteral corticosteroid.
Prednisone
Describe when Beclomethasone is used.
Prescribed as maintenance TX of asthma & as prophylactic therapy in pts 5+
Also used in tx of asthma in pts who require oral therapy to reduce or eliminate need for systemic corticosteroids
When may Beclomethasone be a bad choice in treatment?
Care needed in pts who are transferred from systemically active corticosteroids to beclomethasone because deaths due to adrenal insufficiency have occurred in asthmatic pts during and after transfer form systemic corticosteroids to less systematically available ICS
After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamus-pituitary-adrenal (HPA) function
Describe when and when not to use Budesonide.
Use for maintenance of tx of asthma as prophylactic therapy in adult and pediatric pts 6+ yo
Caution = drug shouldn’t be used where primary tx of status asthmaticus or other acute episodes of asthma where intensive measures are required. Severe hypersensitivity to milk proteins and any of the ingredients in Budesonide is contraindicated
Describe when and when not to use Ciclesonide.
Prescribed as ICS indicated for maintenance of tx of asthma as prophylactic therapy in adult and adolescent pts 12+
Caution = Not indicated for relief of acute bronchospasm. Use not recommended in presence of candida albicans infection of mouth and pharynx, tuberculosis, fungal, bacterial, viral, or parasitic infection
Describe when and when not to use Flunisolide.
Indicated in maintenance tx of asthma as prophylactic therapy in adult and peds pts 6+. Also for asthma pts requiring oral corticosteroid therapy, where adding Flunisolide therapy may reduce or eliminate need for oral corticosteroids
Describe when and when not to use Fluticasone.
Maintenance tx of asthma as prophylactic therapy in pts 4+. Not indicated for relief of acute bronchospasm
Caution = candida albicans infection of mouth and pharynx may occur. Monitor. Advise pts to rinse mouth with water without swallowing after inhalation to reduce risk
Describe when and when not to use Mometasone.
Maintenance of tx of asthma as prophylactic therapy in pts 4+
Caution = use of drug is contraindicated in pts with status asthmaticus or other episodes of asthma where intensive measures are required. Also, contraindicated in pts with hypersensitivity to milk proteins or any ingredients of drug.
Describe when and when not to use Triamcinolone.
Indicated in maintenance tx of asthma as prophylactic therapy
Also for asthma pts who require systemic corticosteroid administration, where adding this agent may reduce or eliminate need for systemic corticosteroids
Not indicated for relief of acute bronchospasm
Caution = contra in primary tx of status asthmaticus or other acute episodes of asthma where intensive measure are required. Particular care needed in pts who are transferred from systemically active corticosteroids to triamcinolone b/c death due to adrenal insufficiency have occurred in asthmatic pts during and after transfer from systemic corticosteroids to aerosolized steroid therapy
When are oral corticosteroids used? Are they likely to cause side effects?
Used in combo with SABA to treat moderate to severe asthma flare-ups
More likely to cause side effects than ICS
Describe when and when not to use Prednisone.
Used as anti-inflammatory or immunosuppressive agent for certain allergic, dermatologic, GI, hematologic, ophthalmologic, nervous, renal, resp, rheumatologic, specific infectious dz or conditions and organ transplantation
Also used for Tx of certain endocrine conditions and for palliation of certain neoplastic conditions
Caution = may lead to HPA axis suppression. Monitor pts for Cushing’s and hyperglycemia with chronic use and taper doses gradually for withdrawal after chronic use
Name the leukotriene receptor antagonists/lipoxygenase inhibitors.
Zafirlukast
Montelukast
What are the characteristics of leukotriene receptor antagonists?
Selective reversible antagonists of CysLT1 receptors
Taken orally
Bronchodilators
Anti-inflammatory action
Less effective than ICS
Have glucocorticoids sparing effect (potentiate corticosteroid action)
Name the Lipoxygenase inhibitor.
Zileuton
What is the use for leukotriene antagonists?
Among most prescribed drugs for management of asthma, used both for treatment and prevention of acute asthmatic attacks
What are the leukotriene mediated effects of asthma? What is the MOA of leukotriene antagonists?
Effects include airway edema, smooth muscle contraction, and altered cellular activity assoc with inflammatory process
Acts by binding cysteinyl leukotriene (CysTL) receptors and blocking activation and the subsequent inflammatory cascade which cause symptoms commonly assoc with asthma and allergic rhinitis
Describe the characteristics of Montelukast.
Orally active compound with high affinity and selectivity to cysLT1 receptor
Inhibits physiologic actions of LTD4 at the cysLT1 receptor without any agonist activity
Describe when and when not to use Montelukast.
Primarily prescribed to treat allergies and prevent asthma attacks
Contra = not indicated for use in reversal of bronchospasm in acute asthma attacks, including status asthmaticus
-therapy can be continued during acute exacerbations, but pts should have a SABA available
Describe characteristics of and when/when not to use Zafirlukast.
Selective and competitive receptor antagonist of LTD4 and LTE4, components of slow reacting substance of anaphylaxis (SRSA)
Prescribed for prophylaxis and chronic treatment of asthma in adults and children 5+
Caution = hepatotoxicity, cases of life-threatening hepatic failure have been reported in pts treated with drug
Describe characteristics of and when/when not to use Zileuton.
Inhibitor of 5-lipoxygenase and thus inhibits leukotriene formation
Used as prophylaxis and chronic tx of asthma in adults and children 12+
NOT used to treat an acute asthma attack
Caution = not recommended in cases where active liver dz or persistent hepatic function enzyme elevations are >3x upper limit of normal
Name the monoclonal antibody drug used to treat asthma.
Omalizumab
What are the actions of Omalizumab?
1) Binds to free IgE, decreasing cell-bound IgE
2) Decreases expression of high-affinity receptors (FCeRI on mast cells)
3) Decreases mediator release
4) Decreases allergic inflammation and prevents exacerbation of asthma and reduces sx
Describe the indications of Omalizumab.
Anti-igE antibody indicated for moderate to severe persistent asthma in pts 6+ with positive skin test or in vitro reactivity to a perennial aeroallergen and sx that are inadequately controlled with inhaled corticosteroids
Also indicated in tx of chronic idiopathic urticaria in adults and 12+ who remain symptomatic despite H1 antihistamine tx
Describe the contraindications of Omalizumab.
contra = anaphylaxis - administer only in healthcare setting prepared to manage anaphylaxis that can be life-threatening and observe pt for appropriate period of time after administration
How do you treat pts who have an overlap between asthma and COPD sx?
Triple therapy with ICS, LABA, and LAMA