asthma
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| RESPIRATORY/ASTHMA - PLATTNER |
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| what are characteristics of acute obstrucitve disease episodes (time course - 2) | 1) intermittent; 2) reversible
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| what is asthma characterized by | reversible inflammation of airway wall
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| what age/sex is asthma incidence highest | boys in early childhood
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| what is happening to overall asthma incidence | increasing
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| when in the day are asthma symptoms the worst | night and early morning
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| what are the two main types of asthma | 1) extrinsic/allergic; 2) intrinsic/idiopathic
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| which is more common in adults | intrinsic/idiopathic (allergic asthma begins in childhood, less common in adults)
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| what does the hygiene hypothesis suggest that allergic asthma is due to | an imbalance in Th1/Th2 cells
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| when will children have the right balance of Th1/Th2 cells | when they are exposed to childhood infections
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| what are Th1 cells and Th2 cells responsible for | protective immunity, inflammation/cytokines
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| what immune response (Th1 or Th2) predominates if children are not exposed to infections early | Th2 - asthma is more likely
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| patients with what problems often experience intrinsic/idiopathic asthma | those with nasal polyps or sinusitis
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| what is the most common asthma trigger | exercise
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| when is strenuous exercise particularly likely to trigger asthma | cold weather
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| what drugs/classes were said to trigger asthma (2) | 1) NSAIDs; 2) aspirin
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| what else are asthma triggers (list) | pollen, dander, mites, cigarette smoke, sulfites (preservatives) food coloring, chemicals, cleaners
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| define: asthma asthma is a narrowing of the bronchi due to an underlying chronic inflammatory disorder |
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| what cells play a role in the inflammation of asthma (list) | mast cells, eosinophils, T-cells, macrophages, neutrophils, and epithelial cells
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| what are the three important featuers of asthma | 1) chronic airway inflammation; 2) airway hyper-reactivity; 3) airflow obstruction
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| what spirometry measurements are relevant to asthma (3) | 1) FEV1 (forced expiratory volume in one second); 2) FVC (total volume expired from one expiration); 3) PEFR (maximum flow rate during forced expiration)
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| how can one test the reversibility of an obstructive lung condition (test and result) | perform spirometry before and after inhaling a short-acting bronchodilator - one should see an increase of 12% or 180 ml in FEV1 after inhaling the drug - patients with asthma are hyper-responsive to these stimuli
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| who is spirometry not good for (3) | 1) young; 2) very old; 3) very sick
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| what does PEFR measure | diurnal variation in airway obstruction - indicator of asthma control
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| what worsens hyper-responsiveness to irritable stimuli in asthma patients | exposure to allergen
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| for diagnosis, what test is done, related to hyper-responsiveness | asthma patients are challenged with irritable stimuli and fall in FEV1 is measured
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| what are children challenged with, and adults challenged with | children: exercise; adults: bronchoconstrictor (histamine, methacholine)
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| what measurement is obtained in adults, besides FEV1 | the amount of bronchoconstrictor needed to reduce FEV1 by 20%
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| how is sputum induced for the sputum test | by inhalation of hypertonic saline
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| what is done with the sputum | analyze the inflammatory cells in the airways
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| what cells are predominant in normal individuals (2) | 1) macrophages; 2) neutrophils
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| in asthma patients, what inflammatory cells will be most increased | eosinophils (and also neutrophils, sometimes)
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| what drug, and type of response, is increased eosinophilia associated with | good response to corticosteroids
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| what happens in the acute immediate response | intense bronchoconstriction
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| what causes the late phase reaction | prolonged bronchoconstriction
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| what occurs in the late phase reaction (4) | 1) edema; 2) increased mucous secretion; 3) hyper-reactivity; 4) thickening of airway wall
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| what innervation mediates bronchoconstriction | cholinergic nerve (vagal) innervation
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| what receptors mediate bronchoconstriction | adenosine
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| what receptors mediate bronchodilation | beta-2 adrenergic - these are present on bronchial smooth muscle and throughout the respiratory tract
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| what is the "traditional asthma theory" | asthma comes from altered balance between adrenergic/cholinergic stimulation, and is based on the fact that beta-2 agonists as well as cholinergic muscarinic antagonists provide relief
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| what is evidence against this theory | inhibiting beta-adrenergic receptors does not induce bronchial hyper-reactivity or asthma symptoms in normal individuals
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| what is the role of the vagus nerve | it senses allergens and sends a signal to the CNS, which sends a signal back, causing the release of acetylcholine, which binds muscarinic receptors on airway smooth muscle and induces bronchial constriction
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| what cytokines cause bronchoconstriction (2) | 1) IL-4; 2) IL-5
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| what other mediators cause broncohconstriction (3) | 1) histamine; 2) leukotrienes; 3) prostaglandins
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| what cells do these inflammatory mediators recruit, that are most specifically related to asthma | migration and activation of eosinophils
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| what do T helper cells secrete in response to antigen | lymphokines
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| what is the role of Th2 cells in asthma | induce inflammation
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| what does Th2 cell release that activates eosinophils | IL-5
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| what other cells do Th2 cells activate | neutrophils
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| what do Th2 cells induce B cells to do, related to asthma | secrete IgE, which binds to surface of mast cells
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| what do substances released by eosinophils and neutrophils cause (5) | 1) damage to epithelial cells; 2) mucus secretion; 3) hyper-reactivity; 4) bronchospasm; 5) smooth muscle contraction
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| what two types of cells are most associated with leukotriene release | 1) eosinophils; 2) mast cells
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| at what point does airway remodeling occur | after prolonged allergen exposure and long-term airway inflammation
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| what happens to epithelial cells in remodeling (2) | 1) desquamation; 2) disruption
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| what remodeling change causes increased mucus secretion | goblet cell hyperplasia
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| what cells are recruited in airway remodeling (3) | 1) mast cells; 2) T cells; 3) eosinophils
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| what happens to smooth muscle | increaesd thickness due to hyperplasia or hypertrophy
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| what is deposited in airway remdoeling, and why | matrix (collagen) deposition due to increased fibroblasts
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| what may all of these structural changes eventually cause | obstruction may be only partly reversible
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| what is asthma classification based on, mainly | frequency of symptoms
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| how many classes are there, and what are they called | four - "steps"
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| what is step 1 known as | mild, intermittent
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| how often are symptoms, and what is FEV | <2x/week, >80%
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| what was said about exacerbations | brief
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| what is step 2 known as | mild, persistent
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| how often are symptoms, and what is FEV | >2x/week, >80%
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| what was said about symptoms and exacerbations | may affect activity and sleep
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| what is step 3 known as | moderate, persistent
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| how often are symptoms, and what is FEV | daily, 60-80%
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| what was said about symptoms and exacerbations | affect activity and sleep
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| what is step 4 known as | severe, persistent
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| how often are symptoms, and what is FEV | continuous, <60%
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| what was said about exacerbations | frequent
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| what things are important in management besides pharmacologic therapy (3) | 1) reduce exposure to allergens/irritants; 2) monitor lung function (step 3 and 4); 3) patient education
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| what is done to monitor lung function (2) | 1) record daily PEFR; 2) use personal best and danger zones to manage asthma in home (important to decrease hospital admissions)
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| what is one advantage of aerosol over systemic delivery | fewer serious side effects
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| what % of patients use inhaler devices, and which patient groups do not (2) | about 90% (except small children, and elderly)
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| what size parrticles are deposited in the airway | 1-5 um (smaller are inhaled and exhaled, larger deposited in mouth)
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| what is the use of spacers (2) | 1) limits larger particles; 2) limits need to coordinate inhalation with inhaler activation
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| what other factor affects deposition | breathing rate - need slow, deep breath, held for 5-10 seconds
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| what types of inhalers are used (3) | 1) metered-dose inhalers (MDI); 2) nebulizers; 3) dry powder inhalers
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| which type is most effective | all are equally effective and deliver 1-5 um particles
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| what is a disadvantage of metered dose inhalers | contain chlorofluorocarbons as propellants (but are currently changing over to hydrofluoroalkane for environmental reasons)
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| what are nebulized used for, and in who | severe asthma exacerbations
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| what are two advantages | 1) don't require hand-breathing coordination; 2) can be used with face mask for young children and older patients
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| what are disadvantages (3) | 1) requires power source; 2) requires pressurized gas supply; 3) takes longer to administer
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| what are powders made of that carry drugs in dry powder inhalers (2) | 1) lactose; 2) glucose
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| what are disadvantages of dry powder inhalers (3) | 1) high airflow needed to suspend powder, so bad for young and elderly; 2) poweder can be irritating; 3) temperature and humidity can affect its performance
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| what does activation of beta-2 receptors first cause within the airway smooth muscle cell | activation of adenylyl cyclase and increase in cAMP
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| what does this result in | activated protein kinase A
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| what does protein kinase A cause (2) | 1) inhibits myosin light chain kinase; 2) opens K+ channels
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| what does opening K+ channels lead to | muscle relaxation
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| what other cells do beta-2 agonist affect, and how | prevent mediator release from mast cells by inhibiting function of inflammatory cells through upregulation of cAMP
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| what were these drugs said not to affect, and why | they do not decrease hyper-responsiveness, possibly due to desensitization of receptors after prolonged use
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| how effective are short-acting, inhaled beta-2 agonists, and what are they the DOC for | most effective asthma drugs, DOC for acute asthma
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| how long do they take to work, and how long does effect last | work in 1-5 minutes, duration 2-6 hours
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| by what method(s) are they administered | 1) MDI; 2) nebulizer
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| what inhaled, short-acting beta-2 agonists must we know (3) | 1) albuterol (salbutamol); 2) terbutaline; 3) levalbuterol
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| how does levalbuterol compare to albuterol | it is the R-isomer of albuterol (albuterol has both R and S enantiomers, but only the R enantiomer is pharmacologically active)
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| what is its advantage | slightly lower incidence of adverse effects, but no more effective
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| what are its disadvantages (2) | 1) price; 2) requires nebulizer administration
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| which beta-2 adrenergic agonists can be given orally in slow release forms (2) | 1) salbutamol; 2) terbutaline
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| how does their efficacy compare to inhaled forsm | less efficacceous
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| who are they effective for | young children who can't use MDI or are irritated by nebulizer
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| what other disadvantes do they have (2) | 1) more adverse effects; 2) shorter onset of action
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| how else can these slow-release forms be administered | subcutaneous injection
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| what inhaled, long-acting beta-2 agonists must we know (2) | 1) salmeterol; 2) formoterol
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| which of these drugs may act the soonest, and how quick | formoterol - may work in five minutes
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| what is the duration of these drugs | 12 hours
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| what should these drugs be used for | breakthrough attacks, good for controlling nocturnal asthma - not acute attacks
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| why do they have longer duration | they have long side chains that insert into lipid bilayer of plasma membrane and gradually diffuse
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| what was said about the selectivity of salmeterol | 50X more selective to beta-2 receptors than albuterol
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| what is the dosing regimen for the long-acting inhaled beta-2 agonists | twice daily
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| what is a disadvantage of long-acting inhaled beta-2 agonists | mask worsening airway inflammation
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| what is the consequence of this problem | not recommended as monotherapy
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| what can long-acting inhaled beta-2 agonists be used in conjunction with | corticosteroids
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| what other beta-2 agonists must we know (3) | 1) epinephrine; 2) ephedrine; 3) isoproterenol
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| how can epinephrine be administered (2) | 1) inhaled; 2) injected subcutaneously
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| when does it provide maximum relief, and how long does it last | 15 minutes, 60-90 minutes
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| why is it rarely prescribed | more adverse effects (cardiac)
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| why does it have more adverse effects | it stimulates beta-1 and alpha receptors as well as beta-2
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| what receptors is ephedrine an agonist at | both alpha and beta
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| what does it function as, besides a bronchodilator | decongestant
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| in what way is it used for asthma | to prevent mild to moderate asthma
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| why is it used less extensively now | beta-2 agonists are better
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| what are its adverse effects mentioned (2) | 1) insomnia; 2) hypertension
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| what effect does isoproterenol have, and how is it given | potent bronchodilator which is in microaerosol preparation
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| what side effect may it have | cardiac arrhythmias
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| what effects of the beta-2 receptor were mentioned, besides bronchodilation (4) | 1) vasodilation; 2) decreased GI tone; 3) uterine relaxation; 4) hepatic gluconeogenesis
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| what type of adverse effects arise from beta-1 stimulation | cardiac via stimulation of beta-1 receptors on heart muscle - tachycardia, increased contractility, and conduction
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| what are adverse effects like for inhaled beta-2 agonists | uncommon
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| what skeletomuscular adverse effect arises from oral/IV beta-2 agonists | muscle tremor
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| how can muscle tremor be decreased | starting with low doses
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| what CNS adverse effects arise from oral/IV beta-2 agonists (3) | 1) nervousness; 2) restlessness; 3) anxiety
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| what cardiac adverse effects arise from oral/IV beta-2 agonists (4) | 1) tachycardia; 2) palpitations; 3) arrhythmias; 4) angina
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| which oral/IV beta-2 agonist produces less cardiac effects than some other drugs | albuterol
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| what drugs, if coadministered, increase cardiac adverse effects | MAOIs
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| what additional adverse effects may MAOIs cause | nausea/vomiting
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| why is overutilizing beta-2 agonists dangerous | prolonged use may be associated with near-death from asthma - overuse associated with worsening
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| what criteria determines whether a patient requires more aggresssive anti-inflammatory therapy | if they use the inhaler over 3x/day
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| what underlying mechanisms does long-term use of beta-2 agonists result in (2 problems) | 1) downregulation of receptors; 2) increased hyperreactivity
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| what should be used to monitor the disease | daily PEFR
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| what other misuse of beta-2 agonists has caused death | using a long-acting beta-2 inhaler to treat an acute attack
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| what is the MOA of anticholinergic agents | inhibit muscarinic (M3) acetylcholine receptors, blocking contraction of airway smooth muscle
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| how does bronchodilation compare to beta-2 agonists | bronchodilation is slower and less intense - use has declined with advent of beta-2 agonists
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| what bronchoconstrictor stimuli were anticholinergics said to protect against (2) | 1) dust; 2) cold air
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| what do they not protect against (3) | 1) allergens; 2) exercise triggers; 3) inflammatory cells
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| what anticholinergics must we know (2) | 1) ipratropium bromide; 2) triotropium bromide
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| which is available as a dry powder | triotropium bromide
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| how is ipratropium bromide available | inhaler or nebulizer forms
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| what is ipratropium derived from, and what is the difference between it and its derivative | it is a more selective derivative of atropine
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| which anticholinergic has an advantage, what is it, and what is the magnitude of the advantage | triotropium bromide has a 24 hour duration rather than 6 hopurs
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| why does it have a longer duration | it dissociates from receptors more slowly than ipratropium bromide
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| is the response to anticholinergics consistent among patients | no, it is variable
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| what can anticholinergics be combined with, and what combined form must we know | beta-2 agonists - albuterol + ipratropium (combivent)
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| what is the incidence of side effects with anticholinergic inhalers | low, because of little systemic absorption
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| what adverse effects occur (4) | 1) dry mouth; 2) blurred vision; 3) urinary retention; 4) bitter taste
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| what may these drugs precipitate in the elderly | glaucoma
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| what patients are corticosteroids drugs of choice for | for patients who need to use a beta-2 agonist inhaler >3x/week, and who are step 2-4
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| are they useful for acute attacks, prophylaxis, or both | prophylactically only
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| how long does it take for them to be effective | 6-12 hours
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| why are they administered at ER visits | to prevent recurrence after acute attacks
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| how can they be administered (3) | 1) oral; 2) IV; 3) inhaled
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| how long may it take for maximal improvement to occur | Several weeks
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| what is the mechanism of action of corticosteroids | inhibit airway inflammation by binding to the glucocorticoid receptor in cells
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| what happens when the GR receptor is activated (2) | 1) heat shock proteins are released; 2) GR goes to nucleus and binds genes containing GRE element in promoter and affects transcription of inflammatory genes
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| what is the effect of corticosteroids on smooth muscle activity | no direct effect
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| how do they affect bronchial reactivity | by reducing inflammation
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| how do they interact with beta-2 agonists | they restore sensitivity to beta-2 agonists
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| what is the long term effect of corticosteroids on bronchial reactivity | unlike beta-2 agonists, prolonged use reduces bronchial reactivity
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| what is the effect of corticosteroids on late-phase inflammatory response, and what specific example was given | decrease late-phase response, such as scar formation
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| what is the mechanism of the effect of corticosteroids on inflammation (list of many effects) | modulate cytokine/chemokine production, inhibit chemotaxis, prevent leukotriene release, prevent basophil, eosinophil, and leukocyte accumulation in lung tissue
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| how does effectiveness vary among corticosteroids | all are equally effective
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| which corticosteroids can be given by metered dose inhaler (5) | 1) beclomethasone; 2) budesonide; 3) flunisolide; 4) trimacinolone; 5) fluticasone
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| which of these have a nebulizer formulation (2) | 1) budesonide; 2) fluticasone
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| what corticosteroid is given IV, and for what patients | hydrocortisone, for patients with respiratory failure or GI upsets
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| what other oral-systemic corticosteroid is given, and how long is the treatment course | oral-systemic prednisolone for 5-10 days
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| what local effects can inhaled corticosteroids have, at normal doses (2) | 1) voice (loss, hoarseness, weakness); 2) oral candidiasis
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| at higher doses, what adverse effects can happen (3) | 1) suppression of hypothalamic/pituitary axis and adrenal suppression; 2) osteoporosis; 3) cataracts
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| what can reduce voice effects | reduction of dose
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| what can be done to protect against candidiasis (2) | 1) rinse mouth and throat after use; 2) use a spacer (reduces incidence)
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| what can systemic use of oral corticosteroid cause (long list of adverse effects) | fluid retention, weight gain due to increased appetite, osteoporosis, skin bruising (dermal thinning) hypertension, cataracts, diabetes, peptic ulcers, psychosis, susceptibility to infections, HPA suppression and adrenal suppression, inhibition of growth
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| what is important to do with these drugs to avoid adrenal suppression | taper off drug
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| why are these drugs used, despite all of the adverse effects | the small risk of adverse effects is outweighed by the risk of inadequately controlling severe asthma
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| what type of prophylactic preparation (mixed with corticosteroids) can be used for patients not adequately controlled by steroids alone | use of long acting beta-agonist with low to medium doses of inhaled corticosteroids
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| what example of this combination (name and two drugs used) is available in the US | advair - combination of salmeterol and fluticasone
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| what mast cell degranulation inhibitor is available for all ages | cromolyn sodium
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| which is available for adults only (12 years and up) | nedocromil sodium
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| what is the mechanism of action of these drugs (2) | 1) inhibit activation of delayed chloride channels in cell membrane of mast cells and eosinophils, which inhibits their activation; 2) inhibits coughing by inhibiting airway nerves
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| what other cells was it said to inhibit, and what is the result | inhibits eosinophils, preventing inflammatory response to inhaled allergens
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| what components of asthma were mast cell degranulation inhibitors said to affect (2) | 1) reduce bronchial reactivity; 2) inhibit late-phase asthma responses to allergens/exercise
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| are they effective in acute attacks | no - no effect on smooth muscle tone, and do not inhibit bronchospasms
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| what forms are mast cell degranulation inhibitors given in | 1) aerosol spray; 2) nebulizer
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| what was said about their absorption and excretion | poorly absorbed (1%) and excreted unchanged in urine and bile
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| when does peak concentration occur, and how long does it last | occurs 15 minutes after inhalation and last 45 to 100 minutes
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| how effective are mast cell degranulation inhibitors | less effective than corticosteroids - used as alternative to oral or inhaled beta-agonists - use in US is decreasing due to limited efficacy
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| how common are adverse effects | well-tolerated
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| what effects can occur (6) | 1) laryngeal edema; 2) joint swelling; 3) headache; 4) rash; 5) nausea; 5) rarely, anaphylaxis
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| which drug must we know in this class [anti inflam] | obalizumab
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| what is its mechanism of action, and what does it act upon | biological drug - recombinant humanized monoclonal antibody against IgE - binds free IgE so it cannot bind mast cells
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| what is the bioavailability of obalizumab (%) | 60%
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| how long does it take to reach peak serum levels | 7-8 days
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| how long does it take for the drug to be eliminated | 26 days
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| what are the disadvantages (2) | 1) expensive; 2) single SQ injection every 2-4 weeks
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| who should this drug be given to | patients with severe asthma that is not well controlled by standard drugs (corticosteroids + long-acting beta-2 agonists)
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| what is the incidence of side effects like | well-tolerated
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| what side effects can occur (3) | 1) low antibody titers; 2) injection site reaction; 3) anaphylaxis (0.1%); 4) higher frequency of malignancies occur in patients taking it (but not sure that this is due to the drug)
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| LEUKOTRIENE MODIFIERS |
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| what is secreted from mast cells after activation, but later than histamine, and what is caused in the lungs | leukotrienes are secreted - induces SM contraction in airways, but slower rate than histamine
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| what are leukotrienes synthesized from, and where | arachadonic acid in the nuclear membrane of inflammatory cells
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| what leukotrienes were said to be potent bronchoconstrictors (class) and how potent were they said to be | cysteinyl leukotrienes (cysLT) - 1000x as potent as histamine
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|
||||
| what leukotrienes belong to this class (cysLTs - 3) | LTC4, LTD4, LTE4
🗑
|
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| so, what induces the secretion of the cysLTs | IgE crosslinking
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|
||||
| what induces eosinophils to produce cysLTs | adhesion, migration
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|
||||
| where can these cysLTs be detected in asthma patients (2) | 1) bronchoalveolar lavage fluid; 2) urine
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|
||||
| what were asthmatics said to be 25-100 fold more sensitive to than non-asthmatics | LTD4
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|
||||
| what are the effects of leukotrienes, besides potent bronchoconstriction (4) | 1) induce vascular leakage; 2) edema of airway wall; 3) stimulate mucus secretion; 4) cause eosinophil chemotaxis
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|
||||
| what classes of leukotriene modifiers must we know (2) | 1) leukotriene receptor antagonists (LTRAs); 2) leukotriene synthesis inhibitors
🗑
|
||||
| what LTRAs must we know (2) | 1) zafirlukast; 2) montelukast
🗑
|
||||
| what receptor do LTRAs antagonize | cys-LT1 receptor
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|
||||
| what three things do they block leukotriene action on | 1) mast cells; 2) eosinophils; 3) airway smooth muscle
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|
||||
| what actions do they inhibit (4) | 1) bronchoconstriction; 2) inflammation; 3) edema; 4) leukocyte chemotaxis
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|
||||
| what types of asthma are these drugs useful for | 1) exercise-induced; 2) nocturnal
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|
||||
| what spirometric measurements were they said to improve (2) and how strong is the effect | 1) FEV1; 2) PEFR - modest effect
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|
||||
| what were they said not to be effective as | bronchodilators
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|
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| are LTRAs used for acute or prophylactic treatment, or both | prophylactic
🗑
|
||||
| what % of patients will not respond | 50% - many nonresponders
🗑
|
||||
| how efficaceous are these drugs considered to be, and when are they used | not as efficaceous as moderate to high dose steroids - considered second-line therapy for moderate to severe asthma
🗑
|
||||
| what can LTRAs be used in conjunction with (2) | 1) beta-agonists; 2) steroids
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|
||||
| which can be used for children | montelukast
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|
||||
| which can be given just once daily | montelukast
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|
||||
| which has higher bioavailability | zafirlukast (90% vs 60%)
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|
||||
| which has a longer half life | zafirlukast (but effect is not as long, as the parent drug is responsible for effects, rather than the metabolites)
🗑
|
||||
| which LTRA must be taken on an empty stomach | zafirlukast
🗑
|
||||
| why is compliance better with LTRAs than with inhaled steroids | don't have to learn to use an inhaler
🗑
|
||||
| which one of these drugs has a drug interaction, and what is it | zafirlukast may interact with warfarin
🗑
|
||||
| which LTRA has fewer adverse effects | montelukast
🗑
|
||||
| what rare adverse effect may occur | Churg-Strauss syndrome
🗑
|
||||
| what is Churg-Strauss syndrome, and what is it characterized by (3) | a rare autoimmune syndrome characterized by: 1) eosinophilia in lungs; 2) vasculitis; 3) flu-like syndromes
🗑
|
||||
| what other adverse effects may occur (5) | 1) abnormal liver function tests; 2) nausea/vomiting; 3) GI upset; 4) rash; 5) headaches
🗑
|
||||
| what can Churg-Strauss syndrome be treated with | corticosteroids
🗑
|
||||
| when in asthma treatment might this syndrome arise | unmasked when patients reduce or eliminate the amount of oral corticosteroids
🗑
|
||||
| what leukotriene synthesis inhibitor must we know | zileuton
🗑
|
||||
| what is the MOA of zileuton | inhibits 5' lipoxygenase and inhibits lipoxygenation of arachidonic acid
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|
||||
| what does this in turn inhibit | synthesis of all leukotrienes
🗑
|
||||
| besides bronchoconstriction, what other function does zileuton inhibit | chemoattraction of WBC
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|
||||
| which leukotriene was said to be a WBC chemoattractant | B4
🗑
|
||||
| what is the effects of zileuton on cysLT production (what % blocked) | 70% blocked
🗑
|
||||
| what is the dosing regimen and mode of administration | has to be administered four times daily, orally, as it is a short-acting drug
🗑
|
||||
| what is the main side effect associated with zileuton | acute liver disease
🗑
|
||||
| what test indicates liver toxicity with zileuton | elevation of liver enzymes within the first two months
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|
||||
| what drug interactions does zileuton have, and how does it affect these drugs | 1) theophylline; 2) warfarin - decreases clearance
🗑
|
||||
| what precaution should be taken if theophylline is used with zileuton | dose should be reduced by half
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|
||||
| how often is zileuton used | not used in US due to pharmacologic/safety issues
🗑
|
||||
| what drug is theophylline related to, and what class are these drugs in | closely related to caffeine - both are methylxanthines
🗑
|
||||
| what is the main effect of theophylline | bronchodilator - smooth muscle relaxant
🗑
|
||||
| what other beneficial effects does it have | anti-inflammatory
🗑
|
||||
| what other effects does theophylline have, that are not related to asthma (3) | 1) CNS stimulant; 2) cardiovascular stimulant; 3) decreases peripheral vascular resistance
🗑
|
||||
| what are the three mechanisms of action of theophylline | 1) blocks adenosine receptors; 2) activates histone deacetylaces; 3) inhibits phosphodiesterase
🗑
|
||||
| what is the function of adenosine in asthmatics | bronchoconstrictor (but not in normal individuals)
🗑
|
||||
| when is adenosine released into the circulation in asthmatics, and what is its effect | released into circulation following allergen challenge, and enhances mast cell activation
🗑
|
||||
| where were adenosine receptors said to be present (2) | 1) SM cells; 2) inflammatory cells
🗑
|
||||
| what are the function of HDACs (histone deacetylases) that are blocked by theophylline | HDACs bind HAT/CBP complexes, and prevent them from binding to histones and acetylating them
🗑
|
||||
| what is the effect | represses gene transcription of proinflammatory genes
🗑
|
||||
| besides HDACs, what else binds HAT/CBP complexes, and represses these same genes | glucocorticoids
🗑
|
||||
| what proinflammatory genes were mentioned (2) | 1) GM-CSF; 2) IL-8
🗑
|
||||
| what drugs does theophylline potentiate the effect of | corticosteroids (both inhibit HAT/CBP complexes, and corticosteroids bring HDACs in close proximity to HAT complexes)
🗑
|
||||
| what is the effect of theophylline blocking phosphodiesterase (increases 2 substances) | 1) cAMP; 2) cGMP
🗑
|
||||
| what effects does blockage of phosphodiesterase have on asthma (2) | 1) bronchodilation; 2) blocks synthesis/release of inflammatory mediators
🗑
|
||||
| how does it block release of inflammatory mediators, and from what cells (2) | by inhibition of PDE4 - blocks synthesis/release from mast cells, basophils
🗑
|
||||
| how can theophylline be given (2) | 1) oral (liquid, coated, sustained release); 2) parenteral
🗑
|
||||
| what dosing strategy is used to minimize side effects | low dose for three days, with increase if tolerated, and necessary
🗑
|
||||
| what slows the rate of absorption (2) | 1) food; 2) sleep
🗑
|
||||
| what was said about theophylline and pregnant/nursing mothers | secreted into breast milk, crosses placenta
🗑
|
||||
| how is theophylline eliminated | liver
🗑
|
||||
| how does half-life of theophylline differ between adults and children | longer in adults (8-9 hours) than young children (3-4 hours)
🗑
|
||||
| what medical conditions can increase half-life of theophylline (3) | 1) CHF; 2) cirrhosis; 3) pulmonary edema
🗑
|
||||
| what drug increases its half life | erythromycin
🗑
|
||||
| what drugs decrease the half-life of theophylline (3) | 1) cigarettes; 2) barbiturates; 3) oral contraceptives
🗑
|
||||
| why can theophylline be toxic and even fatal if administered too fast | cardiac arrhythmias
🗑
|
||||
| what can occur prior to signs of toxicity | seizures
🗑
|
||||
| what are signs of toxicity (list) | headache, palpitation, nausea, dizziness, hypotension, tachycardia, restlessness, agiation, emesis
🗑
|
||||
| what are behavioral signs of toxicity | panic, anxiety, fear
🗑
|
||||
| when is theophylline used | as an add-on/second line therapy for patients who are not controlled with low dose corticosteroids
🗑
|
||||
| what drugs are better, and have fewer side effects | beta-2 agonists
🗑
|
||||
| how well does theophylline work when combined with corticosteroids (what can it be compared to) | works as well as doubling steroid amount
🗑
|
||||
| what does cAMP promote in asthma treatment | bronchodilation
🗑
|
||||
| what drug classes affect cAMP levels, and how does each work | 1) beta-agonists increase cAMP by increasing adenyl cyclase activity; 2) PDE inhibitors slow rate of degradation
🗑
|
||||
| what drug classes inhibit bronchoconstriction (2) | 1) muscarinic antagonists; 2) adenosine antagonists
🗑
|
||||
| what definitive evidence exists that alterantive therapies work for asthma | none
🗑
|
||||
| what alternative drugs were shown to decrease airway resistance | 1) oral THC; 2) ivy leaf extract
🗑
|
||||
| what alternative therapy may worsen the disease | black tea/coffee
🗑
|
||||
| what alternative therapy increased FEV1 in one study | ginkgo biloba
🗑
|
||||
| ASTHMA MANAGEMENT FOR CHILDREN UNDER FIVE for young children, what drugs should be used for quick relief for children under five | use short-acting beta-2 agonist inhalers
🗑
|
||||
| what is standard treatment for children with step 1 asthma | none
🗑
|
||||
| what is the standard treatment for children with step 2 asthma | low dose corticosteroid (inhaled or nebulizer)
🗑
|
||||
| what are alternative treatments for children with step 2 (2) | 1) cromolyn; 2) leukotriene antagonist
🗑
|
||||
| what are standard treatments for children with step 3 asthma (2) | 1) low dose corticosteroid + long acting inhaled beta-2 agonist; 2) medium dose ICS
🗑
|
||||
| if these treatments are insufficient for children with step 3, what should be used | medium dose ICS + long acting beta-2 agonist
🗑
|
||||
| alternatively for children with step 3, what can be combined with medium dose ICS (2) | 1) leukotriene antagonist; 2) theophylline
🗑
|
||||
| what is standard treatment for children with step 4 asthma | 1) high dose ICS; 2) long acting beta-2 agonist
🗑
|
||||
| if necessary, what can be added | oral corticosteroid syrup
🗑
|
||||
| ASTHMA MANAGEMENT FOR ADULTS AND OLDER CHILDREN for adults, what should be used for quick relief | short-acting beta-2 agonist inhalers
🗑
|
||||
| what is the standard treatment for step 2 asthma | low dose ICS
🗑
|
||||
| what are alternative treatments for step 2 for adults (4) | 1) cromolyn; 2) leukotriene antagonist; 3) nedocromil; 4) sustained release theophylline
🗑
|
||||
| what are standard treatments for adults with step 3 asthma (3) | 1) low dose ICS + long acting inhaled beta-2 agonist; 2) medium dose ICS; 3) low dose ICS + theophylline; 4) low dose ICS + leukotriene modifier
🗑
|
||||
| if needed, what change can be made | increase to medium dose ICS + long acting beta-2 agonist
🗑
|
||||
| what are alternative treatments for step 3 asthma in adults (2) | 1) meduim dose ICS + leukotriene antagonist; 2) medium dose ICS + theophylline
🗑
|
||||
| what is the standard treatment for step 4 asthma in adults | high dose ICS + long acting beta-2 agonist
🗑
|
||||
| what can be added, if necessary | oral corticosteroid syrup or tablets long-term
🗑
|
||||
| what change should be made in drug strategy if control is maintained when review is made 1-6 months later | stepwise reduction
🗑
|
||||
| when should a low-dose ICS be added to a beta-2 agonist in mild asthma | if the beta-2 agonist is used >3x / week
🗑
|
||||
| what less-effective alternative can be added to the beta-2 agonist | leukotriene modifiers
🗑
|
||||
| if adding a low dose ICS isn't effective, what can be added (2) | 1) long-actinb beta agonist; 2) leukotriene modifier
🗑
|
||||
| how does the effectiveness of adding a second drug compare to increasing ICS dose | tends to be more effective
🗑
|
||||
| what other therapy can be considered if low dose ICS isn't effective for mild asthma | obalizumab
🗑
|
||||
| who can it be used in | patients over 12 who are not controlled by other drugs
🗑
|
||||
| besides fast-acting beta-2 agonists, what else were said to be helpful for acute exacerbations | oral corticosteroids
🗑
|
||||
| what is most common cause of asthma death | under-treatment
🗑
|
||||
| what measurement should be used by patients to monitor asthma | PEFR
🗑
|
||||
| when should it be monitored | AM and PM
🗑
|
||||
| how is PEFR characterized (what are categories called) and what does each category represent | 1) green zone: 80-100% of personal best; 2) yellow zone: 50-79%; 3) red zone: <50%
🗑
|
||||
| what is the strategy if PEFR is in the yellow zone | adjust medication if PEFR stays in yellow zone after two puffs of beta-2 agonist
🗑
|
||||
| what should be done if PEFR is in the red zone | call provider immediately if beta-agonist doesn't bring PEFR out of red zone
🗑
|
||||
| what should be the first step when someone enters hospital with asthma exacerbation | assess asthma severity - FEV or PEFR, respiratory rate, oxygen saturation
🗑
|
||||
| what should be done if there is impending respiratory arrest (5 things - 3 drugs, 2 actions - do all) | 1) intubate; 2) give nebulized beta-2 agonist; 3) give anticholinergic; 4) IV corticosteroid; 5) admit to ICU
🗑
|
||||
| what should initial treatment be if FEV or PEFR is <50% (severe exacerbation - 2 drugs, frequency of dosing) | give by nebulizer every 20 minutes: 1) inhaled beta-2 agonist; 2) anticholinergic
🗑
|
||||
| what else should be given if FEV <50% (2) | 1) oxygen; 2) oral corticosteroid
🗑
|
||||
| what oxygen saturation should be reached | 90%
🗑
|
||||
| what should be done if FEV or PEFR >50% (2) | 1) beta agonist (up to 3 doses in first hour); 2) oxygen to achieve >90% saturation
🗑
|
||||
| what should be added if no immediate response | oral corticosteroids
🗑
|
||||
| what is considered to be a good response to treatments | PEFR > 70% for one hour
🗑
|
||||
| what should be done if good response is seen | send patient home with treatment
🗑
|
||||
| what drugs should be given (2) | 1) beta-2 agonist; 2) ICS
🗑
|
||||
| what is considered to be incomplete response | PEFR 50-70%
🗑
|
||||
| what should be done | admit to hospital, continue treatment
🗑
|
||||
| what is considered to be poor response | PEFR < 50%
🗑
|
||||
| what drugs should be given if response is poor (3) | 1) inhaled beta-2 agonist hourly; 2) anti-cholinergic; 3) IV corticosteroid
🗑
|
||||
| what other actions shuld be taken (2) | 1) admit to ICU; 2) possible intubation
🗑
|
||||
| what classes of drugs are used for COPD (4) | 1) long acting beta-2 agonists; 2) long acting anti-cholinergics; 3) glucocorticoids; 4) theophylline
🗑
|
||||
| what long-acting beta-2 agonists are used (2) | 1) salmeterol; 2) formoterol
🗑
|
||||
| what long-acting cholinergics is the longer acting | tiotropium bromide
🗑
|
||||
| which long-acting cholinergic was said to be used for patients with a partially reversible component | ipratropium bromide
🗑
|
||||
| how effective are glucocorticoids for COPD, what treatment course is used, and when are they most effective | some respond to short course -mixed results as to efficacy, except if there is an acute bronchospasm episode
🗑
|
||||
| what is theophylline used with in COPD | beta-2 agonist
🗑
|
||||
| what is the treatment for emphysema in patients with alpha-1-antitrypsin deficiency (AKA alpha-1-antiproteinase) | purified alpha-1-antiprotease (prolastin) - IV
🗑
|
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