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54 Cards in this Set
- Front
- Back
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asthma is _________
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a chronic inflammatory disorder
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Many mediators are released that may cause _____ and ________.
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edema and bronchoconstriction
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Many mediators are released that may cause edema and bronchoconstriction. these are...(3)
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Histamine
Leukotrienes Prostaglandins |
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_________ and _______ are key in managing asthma.
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Bronchodilators
anti-inflammatory corticosteroids |
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Inhaled Corticosteroids (5)
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beclomethasone
triamcinolone flunisolide budesonide fluticasone |
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Systemic Corticosteroids (3)
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prednisone
prednisolone methylprednisolone |
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Long acting beta2 agonists (2)
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salmeterol
formoterol |
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Cromones (2)
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cromolyn
nedocromil |
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Leukotriene modifiers (3)
indication? |
montelukast
zafirlukast zileuton aspirin-sensitive asthma, adjunctive with anti-inflammatory |
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Long term control meds (Maintenance) (7)
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Inhaled Corticosteroids
Systemic Corticosteroids Cromones Long acting _2 agonists Combined medication Leukotriene modifiers Theophylline |
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QUICK RELIEF (RESCUE DRUGS) (3)
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Inhaled ß2 agonist
Anticholinergics Systemic corticosteroids |
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QUICK RELIEF (RESCUE DRUGS)
Inhaled ß2 agonist (3) indications? |
albuterol
pirobuterol terbutaline PRN for acute symptoms, exercise induced asthma |
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QUICK RELIEF (RESCUE DRUGS)
Anticholinergics indications? |
Ipratropium bromide
acute broncho-spasms |
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QUICK RELIEF (RESCUE DRUGS)
Systemic corticosteroids indications? |
prednisone
prednisolone methylprednisolone acute exacerbations |
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Step Up treatment?
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Start at initial level of severity; gradually step up as needed to gain and maintain control.
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Step Down treatment?
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Start high to gain control and step down.
Start with higher doses .. Stronger meds to get control … Review treatment every 1 – 6 months with the idea of a gradual reduction in treatment |
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Step UP tretament
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Start with least intense treatments .. If control is not maintained …. Consider step up
Be sure pt can administer drugs correctly, is complying and avoiding environmental triggers |
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Asthma under control considered to be? (6)
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Minimal need for ‘PRN’ SABA
NO acute episodes (visits to ER) No limitation of activity No nocturnal episodes Normal pulmonary functions Minimal or no drug adverse effects |
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SUMMARY OF STEPUP APPROACH
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As progress in severity of disorder
Increase the strength, dose, duration, and number of drugs used to control the asthma The toxicity of the drugs increases as you progress in intensity of treatment ALL patients will have …. SABA available for PRN use As severity of disorder progresses .. Dose of ICS will increase … and may eventually use SYSTEMIC CS |
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Bronchodilatory agents (3)
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ß2 agonists
Methylxanthines Anticholinergics |
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Antiinflammatory agents (3)
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Corticosteroids
Inhibitors of mast cell degranulation Leukotriene antagonists |
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BRONCHODILATORS - beta2 agonists
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Stimulation of beta2 receptors produces bronchodilation
Non-selective agonists ( isoproterenol, epinephrine and ephedrine) also affect the heart Epi and iso … have short duration; ephedrine is longer but a risk of CNS |
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BRONCHODILATORS - beta2 agonists
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beta2 agonists act as FUNCTIONAL ANTAGONISTS (physiological antagonists) to produce bronchodilation …minimal effects on heart
TOLERANCE ….. Significance controversial Occurs with systemic effects but minimal on bronchioles CS can reverse … and often used in combination Limiting side effects of oral preps …. MUSCLE TREMOR AND TACHYCARDIA |
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BRONCHODILATORS - beta2 agonists
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Chronic use of long acting beta2 agonists in asthma is controversial
Tendency to produce tolerance making emergency use of SABA less effective Increased risk of cardiovascular problems Conflict of interest of docs doing studies to promote long term use as being safe |
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METHYLXANTHINE BRONCHODILATORS
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Secondary agents today
Used as adjuncts of _2 agonists and ICS Lower efficacy than _2 agonists and ICS Narrow TI ….. Need to use TDM Work as functional antagonists |
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METHYLXANTHINE BRONCHODILATORS
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Slower acting than short acting beta2 agonists
NOT USEFUL FOR ACUTE ASTHMA ATTACKS! Used as alternative for Maintenance therapy Used for long term control and prevention of symptoms … especially NOCTURNAL ASTHMA |
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METHYLXANTHINE BRONCHODILATORS
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Primary drug is THEOPHYLLINE
AMINOPHYLLINE is ethylenediamine complex with theophylline is used most frequently Theophylline is available in slow release forms for long effects (12 – 24 hours) |
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METHYLXANTHINE BRONCHODILATORS
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MECHANISM OF ACTION:
Primary effect in asthma is bronchodilation But does have several other effects Methylxanthines produce effects by: Inhibiting phosphodiesterase Blocking adenosine receptors Altering cellular handling of Ca++ TOLERANCE … does not seem to develop to effects in lung |
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Primary effects of theophylline
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Relax bronchioles
Increase force of diaphragm contraction and decrease fatigue of diaphragm CNS stimulation Increase of force and rate of contraction of heart Increased GI motility and secretions Mild diuresis antiinflammatory?? |
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Theophylline (METHYLXANTHINE) interactions
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Cimetidine, erythromycin & clarithromycin, ciprofloxacin and fever ….. inhibit theophylline metabolism
Smoking, antiepileptics, and RIFAMPIN induce metabolism of theophylline |
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METHYLXANTHINE BRONCHODILATORS ADVERSE EFFECTS?
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heart and CNS
N & V CNS stimulation ….. seizures Anxiety Tachyarrhythmias |
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Theophylline
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Theophylline has a narrow TI and erratic bioavailability ….. So we need to watch the blood levels!!! TDM
Safe range 5 – 15 µg/ml Loading dose usually given when therapy is initiated |
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Theophylline
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Useful adjunct to beta2 agonists and ICS
Narrow TI means we have to monitor levels Often used to control nocturnal episodes Not useful with an acute asthma attack |
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Bronchodilators - ANTICHOLINERGICS
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Use in asthma is pretty limited
A secondary rescue drug .. Most effective in cases where significant cholinergic mediated bronchoconstriction Most useful in chronic bronchitis and COPD Systemic effects are minimal due to local application and limited absorption Ipratropium (Atrovent) Tiotropium – once a day dosing |
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antiiflammatory agents CORTICOSTEROIDS
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Used both systemically & by inhalation (ICS)
Availability of ICS has been a great advance in asthma management Able to address inflammation and minimize systemic effects Used in both allergic rhinitis and asthma |
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CORTICOSTEROIDS Mechanism
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Act on intracellular receptors to change gene product expression
Reduce inflammation and edema Suppress allergic responses Potentiate beta adrenergic agents by enhancing cAMP production and up regulating receptor level Decrease production of PGs and LTs by inhibiting arachidonic acid formation NO DIRECT EFFECT ON MUSCLE TENSION |
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SYSTEMIC CORTICOSTEROIDS
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Used in severe asthma episodes
Primary SYSTEMIC agents: Prednisone Prednisolone Methylprednisolone Oral for 10 days to control severe asthma Alternate day therapy (ADT) if used longer .. To avoid adrenal suppression |
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CORTICOSTEROIDS .. USED SYSTEMICALLY FOR AN EXTENDED PERIOD MAY CAUSE:
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Adrenal suppression
Osteoporosis Muscle wasting Growth suppression Diabetes Cushings syndrome |
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INHALED CORTICOSTEROIDS
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Are not effective in ACUTE asthma attacks
Usually added to drug regimen when _2 agonists alone are not adequate to control asthma Have minimal side effects because given locally Unpleasant taste Hoarseness and weakness of voice (atrophy of vocal cords) ORAL CANDIDIASIS |
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INHALED CORTICOSTEROIDS INCLUDE: (5)
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beclomethasone (Beclovent)
triamcinolone (Azmacort) flunisolide (Aerobid) fluticasone (Flovent) butesonide (Pulmicort) |
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Combined use of Long acting beta2 agonists (LABA) and ICS
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Address both bronchoconstriction and inflammation
beta2 agonists address early phase ICS address late phase Inflammatory mediators make tissue more responsive to other mediators |
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Combined use of Long acting beta2 agonists (LABA) and ICS
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Potentiation
Combined with _2 agonists, dose of ICS needed is less ICS up regulate _2 receptors making tissue more responsive Compliance ….Improved compliance when the two agents are combined in same product dispenser ADVAIR DISKUS – fluticasone + salmeterol |
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inhibitors of Mast cell degranulation CROMOLYN
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Used prophylactically in allergic rhinitis and asthma
May take a couple of weeks for full effectiveness … soooo not useful for acute asthmatic attacks Not a bronchodilator Inhibits release of histamine from mast cells |
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CROMOLYN
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Adjunctive agent
May serve as alternative to ICS or added to reduce the dose of ICS needed May be useful to help decrease frequency of nocturnal episodes No tolerance Primary adverse effect…. May cause coughing when inhale powder NEDOCROMIL similar to Cromolyn |
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LEUKOTRIENE PATHWAY INHIBITORS
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LTs are mediators of asthma
Produced as lipoxygenase acts on arachidonic acid |
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LEUKOTRIENE PATHWAY INHIBITORS
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LTs produced by lots of inflammatory cells in airways
Basophils mast cells eosinophils macrophages LTB4 …. a chemoattractant LTC3 & LTD4 produce: Bronchonstriction increased bronchial reactivity Mucosal edema mucous hypersecretion |
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LEUKOTRIENE PATHWAY INHIBITORS
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Interfering with actions of LTs or their production is a sound approach to treating asthma
Three main agents: zileuton ….. A lipoxygenase inhibitor zafirlukast … LTD4 receptor inhibitor montelukast …. LTD4 receptor inhibitor |
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LEUKOTRIENE PATHWAY INHIBITORS
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All three are orally effective … but less so than ICS …. Zileuton the least effective
Not effective in acute asthma … Aspirin-sensitive asthmatics (~ 10% of asthma population) are much more responsive Zileuton and zafirlukast inhibit P450 metabolism of warfarin |
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LEUKOTRIENE PATHWAY INHIBITORS
Adverse effects |
Churg – Strauss syndrome*
Montelukast Zafirlukast Hepatotoxic potential for all three |
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ANTIHISTAMINES
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1ST generation aren’t very useful … and some suggest to avoid them cause they tend to dry secretions to aggravate asthma
2nd generation don’t have that problem …. desloratadine has shown potential utility in asthma (antiinflammatory effects) |
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IMMUNOSUPPRESSANTS
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Might be used in steroid-resistant asthmatics
Inhibiting the immune system plasma cells may reduce inflammation process Marginally successful but high risks of toxicity Methotrexate Cyclosporine |
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IMMUNOSUPPRESSANTS
Omalizumab (Xolair) |
Omalizumab (Xolair)
Anti-IgE antibody Targeted against portion of IgE molecule that binds to its receptors on Mast cells. Prevents IgE from interacting with cell surface receptors |
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ASTHMA PATIENT MANAGEMENT
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PATIENT EDUCATION
CONTROLLING FACTORS CONTRIBUTING TO ASTHMA SEVERITY PHARMACOLOGICAL THERAPY |
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FYI CHURG – STRAUSS SYNDROME
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One of many forms of vasculitis (inflammation of vessels)
Occurs in pts with history of asthma or allergy Angiitis in lungs, skin, nerves, abdomen Cause unknown …. But overactivity of immune system suspected Involves … fever, weight loss, sinus inflammation in asthmatics, cough shortness of breath, numbness and weakness of extremities, seizures |
