Term
|
Definition
Reversible narrowing of bronchial airways
Characterized by inflammation
Feature of bronchial hyperactivity |
|
|
Term
| Symptoms Associated with Asthma: |
|
Definition
Wheezing, Bouts of Coughing
Tightness in Chest
Shortness of Breath, Reduced FEV1
Mucous Plugs
Mild: episodic, less severe symptoms
More Severe: Frequent attacks, chronic airway narrowing
Exposure to allergens and irritants; infection - particularly viral respiratory infections |
|
|
Term
Pathogenesis of Asthma:
Increased _____ to inhaled stimuli: allergens and non-allergens leading to _____
____ & _____ infiltration which lead to _____
Pathologic ______ of the bronchial mucosa |
|
Definition
reactivity
bronchospasm
Lymphocytic and eosinophilic
bronchospasm
remodeling |
|
|
Term
| Allergens and irritants -> Directly cause release of _____ mediators (_____ & ______). May activate neural pathways, such as the _____ (_____) pathway |
|
Definition
inflammatory
preformed and induced
cholinergic (PNS) |
|
|
Term
| Enormous variety of mediators are released. Thus, blocker of a single mediator, e.g., antihistamine, is unlikely to be effective in alleviating the symptoms or the progression of asthma. _______, which are capable of blocking many key steps in the inflammatory process, come closest to this ideal therapy. |
|
Definition
|
|
Term
| binding of allergen to specific ____ antibody causes ______ and release of ______ |
|
Definition
Ige
degranulation
mediators |
|
|
Term
| Early phase: Allergen-IgE mediated release of preformed mediators causes ____ and infiltration of more ____. |
|
Definition
|
|
Term
| Late phase: hours later, eosinophils, neutrophils, and other inflammatory cells can cause .... (4) |
|
Definition
reactive hyperemia
edema
cellular inflammation
bronchospasm |
|
|
Term
| Repeated exposure: heightened ___ reactivity to specific and nonspecific stimuli. |
|
Definition
|
|
Term
| In the early reaction, FEV1 decreases _____ and in the late reaction, it decreases _____ |
|
Definition
|
|
Term
Neural Regulators of Bronchiolar Smooth Muscle and Vessel Tone:
Sympathetic Nervous System (NE, Epi)
b2 receptors: .......
a1 receptors: ....... |
|
Definition
b2 receptors: bcauses increase cAMP -> causes relax smooth muscle, decrease in airway resistance, & dilation of blood vessels
a1 receptors: constriction of blood vessels |
|
|
Term
Neural Regulators of Bronchiolar Smooth Muscle and Vessel Tone:
Parasympathetic Nervous System (ACh)
Muscarinic receptors: ..... |
|
Definition
| causes contraction of bronchiolar smooth muscle |
|
|
Term
| NO: Powerful ____ _____ _____ |
|
Definition
|
|
Term
| ___ as a marker for asthma -> it is ____ |
|
Definition
|
|
Term
| NO is ____ after corticosteroid treatment |
|
Definition
|
|
Term
| cGMP: Activated by ____ & ____. Also causes ____ ____ ____ in bronchioles |
|
Definition
nitric oxide and natriuretic peptides
smooth muscle relaxation |
|
|
Term
| Goals of Asthma Treatment: Directly relax bronchiolar smooth muscle via ... (3) |
|
Definition
b adrenergic agonists
muscarinic antagonists
theophylline |
|
|
Term
Goals of Treatment
Reduce inflammation by inhibiting formation/release/action of inflammatory mediators via... (3) |
|
Definition
Corticosteroids
cromolyn (mast cell degranulation)
montelukast (leukotriene inhibitor) |
|
|
Term
| B agonists have a ___ therapeutic window than theoplylline |
|
Definition
|
|
Term
| Drugs used to treat asthma (2-agonists and corticosteroids) have potentially serious adverse side effects when administered ____ . So, ___ application is used to produce high local concentrations of drug in lungs and limit ___ absorption. |
|
Definition
systemically
aerosol
systemic |
|
|
Term
| Aerosol Delivery of Drugs (3 types) |
|
Definition
Metered Dose Inhalers (MDI)-> spacer device is very helpful for some patients
Dry powder inhalers
Nebulizers |
|
|
Term
____ size of aerosol is important.
Also Rate of breathing and breath holding is important. |
|
Definition
|
|
Term
| Even under ideal conditions, __% of inhaled aerosol drug is swallowed. Therefore, ideally the best drugs also have poor absorption from the ___ and/or ___ metabolism in the liver. |
|
Definition
|
|
Term
|
Definition
| with a spacer, larger particles are deposited in chamber before pt inhales = inhaled aerosol is enriched w/ smaller particles which more readily travel to the small airways. |
|
|
Term
| Drug of choice for rapid relief of bronchospasm? |
|
Definition
|
|
Term
| B-Adrenergic Agonists: Highly effective and safe for _____, _____ treatment of asthma. |
|
Definition
intermittent, prophylactic
"but Primarily used as a rescue method. May use it prophylactically in situatios where you know you will be exposed to an allergen. Ex. take it before going to a house where you know there is a cat" |
|
|
Term
Current Emphasis for B-Adrenergic Agonists:
Short Acting b2 stimulants: Intermittent use on an as-needed basis for relief of ____, _____ bronchospasm. |
|
Definition
|
|
Term
B-Adrenergic Agonists Overuse:
_____ intensify with overuse, but a greater danger is the tendency to continue to self-medicate during periods when symptoms are escalating.
To avoid a medical emergency, patients should be encouraged to seek medical attention as soon as possible after they detect a decline in the efficacy of their usual therapeutic regimen. |
|
Definition
|
|
Term
B-Adrenergic Agonists Mechanism of Action:
Stimulate ____ receptor on surface of bronchiolar smooth muscle cells -> This receptor couples to __ protein and activates ____ enzyme leading to increased cellular levels of _____ -> which stimulates phosphorylation cascade that leads to decreased intracellular ____ and smooth muscle ____. They Also inhibit ___ release from ___ cells. |
|
Definition
B2-adrenergic
Gs
adenylyl cyclase
cyclic AMP
calcium
relaxation
mediator
mast |
|
|
Term
| B-adrenergic agonists are _____, and thus, higher affinity/potency at ___-adrenergic receptors than at __-adrenergic receptors. |
|
Definition
|
|
Term
| Selectivity of the b-adrenergic agonists helps limit side effects mediated by activation of __-receptors |
|
Definition
|
|
Term
| Since b-adrenergic agonists are b2 selective, we get vasodilation and that results in ______ |
|
Definition
|
|
Term
| Albuterol is what type of drug? |
|
Definition
| Rapid Acting-Short Duration B2-Adrenergic Agonists |
|
|
Term
| Levalbuterol is what type of drug? |
|
Definition
| Rapid Acting-Short Duration B2-Adrenergic Agonists |
|
|
Term
| Terbutaline is what type of drug? |
|
Definition
| Rapid Acting-Short Duration B2-Adrenergic Agonists |
|
|
Term
| Pirbuterol is what type of drug? |
|
Definition
| Rapid Acting-Short Duration B2-Adrenergic Agonists |
|
|
Term
Rapid Acting-Short Duration B2-Adrenergic Agonists (Pirbuterol, Terbutaline, Levalbuterol, Albuterol)
onset< ___ min duration: ___-___ hr |
|
Definition
|
|
Term
| Salmeterol is what type of drug? |
|
Definition
| Long Acting B2-Selective Agonists |
|
|
Term
| Formoterol is what type of drug? |
|
Definition
| Long Acting B2-Selective Agonists |
|
|
Term
Salmeterol:
___ onset
duration > ___ hours of useful broncholdilation
useful to control ____ asthma symptoms
not suitable for treatment of ___ ___ ____ |
|
Definition
slower
12
nighttime
acute bronchospastic attacks |
|
|
Term
Formoterol
Similar to ____
Not for ___ ___ |
|
Definition
|
|
Term
| Long Acting B2-Selective Agonists don't have much _____ action so are Typically used in combination with inhaled _____ |
|
Definition
anti-inflammatory
corticosteroid |
|
|
Term
| Epinephrine is what type of drug? |
|
Definition
| Less Selective or Nonselective B -Adrenergic Agonists |
|
|
Term
| Isoproterenol is what type of drug? |
|
Definition
| Less Selective or Nonselective B -Adrenergic Agonists |
|
|
Term
| Oral administration of B-Adrenergic Agonists increases incidence of adverse side effects: (4) |
|
Definition
muscle tremor
cramps
cardiac tachyarhythmias
metabolic disturbances |
|
|
Term
Appropriate situations for oral b-adrenergic agonist therapy:
therapy in ___ with upper respiratory tract infections who cannot manipulate inhaler
in ___ asthma exacerbations where inhaler cannot be used or when aerosol is ____ |
|
Definition
children
severe
irritating |
|
|
Term
| ____ & _____ are b-adrenergic agonists available in oral form |
|
Definition
| albuterol and terbutaline |
|
|
Term
| Patients with ___ or ____ are at higher risk of adverse effects of B-Adrenergic Agonists |
|
Definition
cardiovascular disease
diabetes |
|
|
Term
| Adverse Side Effects of B-Adrenergic Agonists: |
|
Definition
Skeletal muscle tremor
CNS: restlessness, apprehension, anxiety, tremors
CVS: tachycardia, dysrhythmias, hyper- or hypotension
hypokalemia
worsen hyperglycemia in diabetics
drug interactions with thyroid, digitalis, methylxanthines |
|
|
Term
| _____ is the drug of choice for treatment of anaphylactic reactions. |
|
Definition
|
|
Term
| Epinephrine: Give SQ (or IM or IV with ___) |
|
Definition
|
|
Term
|
Definition
Bronchodilation
Vasoconstriction -> maintain BP & decrease edema
Inhibition of mediator release |
|
|
Term
Additional Anaphylaxis Treatments (other than Epi)
_____ via nebulizer
IV ______
_________
Secondary therapy:
H1 antagonist - ____
Corticosteroid - ______, ______
______(salt/IV form of theophylline) |
|
Definition
Albuterol
fluids
Oxygen
diphenhydramine
hydrocortisone, methylprednisolone
Aminophylline |
|
|
Term
| Ipratropium bromide is what type of drug? |
|
Definition
| A quaternary muscarinic receptor antagonist |
|
|
Term
| Ipratropium bromide: If given parenterally, effects are like ____ b/c they have a similar structure. However, it is only given as ________! |
|
Definition
atropine -> (Ach antagonist - anticholinergic drug)
inhaled aerosol |
|
|
Term
| Ipratropium bromide is only given as inhaled aerosol and has few side effects, even when swallowed because is ___ absorbed from ___ and does not cross _____ b/c it is a _____ amine = poor diffusion across membranes |
|
Definition
poorly
GI
blood brain barrier
quaternary |
|
|
Term
| ________ mediated bronchospasm is a significant component of airway resistance in some asthmatics and COPD patients, especially psychogenic exacerbations |
|
Definition
Parasympathetic
I belive Ipratropium bromide affects the parasympathetic response b/c it is a muscarinic receptor antagonist? see slide 30 |
|
|
Term
| with Ipratropium bromide, Bronchodilation develops more ___ and is usually less ____ than that produced by B-agonists |
|
Definition
|
|
Term
| with Ipratropium bromide, bronchodilation lasts up to __ hours. |
|
Definition
|
|
Term
| Ipratropium bromide causes ______ |
|
Definition
|
|
Term
| Principal use of ipratropium bromide is in ______ |
|
Definition
|
|
Term
| Ipratropium bromide is Combined with albuterol = ___ |
|
Definition
|
|
Term
| Ipratropium bromide Also used intranasally to reduce secretions in the upper and lower respiratory tract in ____ and chronic ____ syndrome. |
|
Definition
allergic rhinitis
postnasal drip |
|
|
Term
| Tiotropium (Spiriva): newer long-acting agent used for maintenance therapy in _____ & _____; dry powder inhaler device |
|
Definition
| chronic bronchitis and emphysema |
|
|
Term
| Tiotropium is what type of drug? |
|
Definition
a form of Ipratropium bromide
A quaternary muscarinic receptor antagonist |
|
|
Term
| Theophylline is what type of drug? |
|
Definition
| Methylxanthine Bronchodilators |
|
|
Term
| caffeine is what type of drug? |
|
Definition
| Methylxanthine Bronchodilators |
|
|
Term
| theobromine is what type of drug? |
|
Definition
| Methylxanthine Bronchodilators |
|
|
Term
| Methylxanthine Bronchodilators: (3) |
|
Definition
| theophylline, caffeine, theobromine |
|
|
Term
| Methylxanthines are found in (5) |
|
Definition
| coffee, tea, chocolate, cocoa, colas |
|
|
Term
| Methylxanthines diverse cellular actions: (4) |
|
Definition
*block cyclic AMP (cGMP) degradation- phosphodiesterase inhibition*
adenosine receptor antagonists
lower intracellular calcium concentrations
hyperpolarize cell membranes
the last two = increase smooth muscle contractions |
|
|
Term
Main action of Theophylline is ________.
Other effects: (4) |
|
Definition
bronchodilation
CNS stimulation
modest peripheral vasodilation
improved skeletal muscle contractility
and a thiazide-like diuresis |
|
|
Term
Theophylline Therapeutic Use:
Formerly a ___ agent for treatment of asthma
Now has a far less prominent role because:
benefits are modest
___therapeutic window- N&V, HA, anxiety -> seizures, arrhythmias
considerable ___ in absorption and elimination between different patients
monitoring of ___ concentrations is often required |
|
Definition
first-line
narrow
variation
plasma |
|
|
Term
| Nocturnal asthma can be improved with slow-release ____ but inhaled ____ and ___ are probably more effective. Also not used b/c it can cause insomnia. Why? |
|
Definition
theophylline
corticosteroids
salmeterol
B/c it is a stimulant |
|
|
Term
| corticosteroids cause.... |
|
Definition
| reduced inflammation - anti-inflammatory effects |
|
|
Term
Corticosteroid MOA:
corticosteroids are ___ receptor ___ that bind to intracellular receptors that translocate to the cell nucleus and positively or negatively regulate gene transcription. This takes ____.
corticosteroids inhibit the production and release of cytokines, vasoactive and chemoattractive factors, lipolytic and proteolytic enzymes, decrease mobilization of leukocytes to areas of injury, and decrease fibrosis.
Enhance actions of _____ |
|
Definition
steroid
agonists
time
b adrenergic agonists |
|
|
Term
| Corticosteroids have potentially important adverse side effects. However, ____ delivery of the steroid has significantly improved the safety of treatment for moderate to severe asthma. Asthmatics who require inhaled B-adrenergic agonist therapy (resuce inhaler) __-__ or more times weekly are candidates for inhaled steroid therapy. |
|
Definition
|
|
Term
| Beclomethasone dipropionate (Beclovent) is what type of drug? |
|
Definition
|
|
Term
| Budesonide dipropionate (Pulmicort) is what type of drug? |
|
Definition
|
|
Term
| Fluticasone (Flovent) is what type of drug? |
|
Definition
|
|
Term
| what corticosteroid is combined with salmeterol to make (Advair Diskus)? |
|
Definition
|
|
Term
| Asthmatic patients maintained on ____ show improvement of symptoms and lower requirements for “rescue” with a bronchodilator. |
|
Definition
|
|
Term
Inhaled Corticosteroids: Available preparations have equivalent efficacy and potential side effects, but differ in the amount of drug aerosolized per inhaler activation, i.e., high-dose and low-dose.
Therefore, the dose of inhaled steroid must be empirically determined for each patient. |
|
Definition
|
|
Term
| Prednisone is what type of drug? |
|
Definition
| Systemic Corticosteroids - oral |
|
|
Term
| Prednisolone is what type of drug? |
|
Definition
| Systemic Corticosteroids - Oral, Injectable |
|
|
Term
| Methylprednisolone is what type of drug? |
|
Definition
| Systemic Corticosteroids - Oral, Injectable |
|
|
Term
Corticosteroids Systemic Therapy:
Systemic (i.v. or oral) steroid therapy is used in severe asthmatic attacks requiring _____.
For severe asthma, ____ or ____ is given i.v., followed by oral doses and gradual tapering of the dose.
For acute exacerbations, oral is ____ administered for 1 -2 weeks.
Longer treatments require tapering of the dose to account for hypothalamic-pituitary-adrenal suppression. |
|
Definition
hospitalization
prednisone or methylprednisolone
prednisone |
|
|
Term
What is given IV in the ER for severe asthma attacks?
What about actue exacerbation? |
|
Definition
Prednisolone- Injectable
Methylprednisolone- Injectable
Prednisone- Oral for exacerbation |
|
|
Term
| Inhaled Corticosteroids: Potential Side Effects: (8) |
|
Definition
Candidiasis - use spacer device and rinse mouth
Hoarseness - usually resolves
HPA suppression - low risks until high doses
Bone resorption - modest risks
Carbohydrate and lipid - minor risks
Cataracts and skin thinning - dose-related
Purpura - dose-related
Growth retardation – may of concern in children |
|
|
Term
| Cromolyn sodium (Intal) is what type of drug? |
|
Definition
| Cromolyn Compounds (anti-inflammatory agent) |
|
|
Term
| Nedocromil (Tilade) is what type of drug? |
|
Definition
| Cromolyn Compounds (anti-inflammatory agent) |
|
|
Term
Cromolyn compounds are ____ agents that indirectly inhibit antigen-induced ____ and directly inhibit the release of ____ and other autocoids from sensitized mast cells.
May suppress the activating effects of ____ peptides on eosinophils, neutorphils, and monocytes. |
|
Definition
anti-inflammatory
bronchospasm
histamine
chemoattractant |
|
|
Term
| Cromolyn compounds do not ____ relax smooth muscle, therefore they are not useful for control of ___ bronchospasm. So would never use this on someone who needs a rescue inhaler. Cromolyn compounds are primarily ____. When inhaled several times daily, they inhibit both the immediate and late asthmatic responses to antigenic challenge or exercise. |
|
Definition
directly
acute
prophylactic |
|
|
Term
| Nedocromil is a newer compound, somewhat more ___ than cromolyn sodium. |
|
Definition
|
|
Term
| Nedocromil is approved for use is asthmatic patients > ___ years old; cromolyn is approved for ____. |
|
Definition
|
|
Term
Cromolyn compounds Adverse effects:
are ___ and generally ___. |
|
Definition
|
|
Term
| Cromolyn compounds are Used mostly in ___ to ____ asthma as an added therapy or as a prophylactic alternative to inhaled ___ or oral ___. |
|
Definition
mild to moderate
steroids
methylxanthines |
|
|
Term
| Leukotrienes- formed through the action of ___ on arachidonic acid. Synthesized by a variety of ___ cells in the airways: mast cells, eosinophils, macrophages, and basophils |
|
Definition
5-lipoxygenase
inflammatory |
|
|
Term
| Zileuton is what type of drug? |
|
Definition
| Leukotriene Inhibitors -> Inhibit 5-lipoxygenase enzyme |
|
|
Term
| Montelukast is what type of drug? |
|
Definition
| Leukotriene Inhibitors -> Leukotriene (LTD4) receptor antagonist |
|
|
Term
| Leukotriene Inhibitors Improve asthma control but are Not as effective as corticosteroids on bronchiole reactivity and airway inflammation, but nearly = in reducing asthma exacerbations (oral use). Why not as effective on inflammation? |
|
Definition
| b/c they only inhibit one type of inflammatory mediator |
|
|
Term
| Leukotriene Inhibitors Approved for children as young as __ |
|
Definition
|
|
Term
| Leukotriene Inhibitors are Generally well tolerated, but FDA is now investigating ___/___ link |
|
Definition
|
|
Term
| Omalizumab is what type of drug? |
|
Definition
| Monoclonal Antibodies - Antibody against region of IgE that binds to mast cell |
|
|
Term
| Omalizumab Does not activate IgE already bound to _____. But Possible inhibition of IgE _____ |
|
Definition
|
|
Term
| Omalizumab Lessens asthma ___ and reduces ___, decreasing need for corticosteroids and hospitalizations |
|
Definition
|
|
Term
| With Omalizumab, ______ reported in ~ 0.2% of patients, so is restricted to most severe asthmatics, who have documented ____ |
|
Definition
|
|
Term
Other Considerations:
Allergy Testing
-Desensitization
Control of Environment
- Removal/reduction of allergens
- Removal/reduction of irritants
- Air purifiers |
|
Definition
|
|
Term
| FEV 1 ____ as you progress from intermittent to severe |
|
Definition
declines
*this is all she said we need to know of slide 50 |
|
|
Term
| ___ dose ICS treats the inflammation the best |
|
Definition
|
|
Term
| Chronic Obstructive Pulmonary Disease (COPD) (2) |
|
Definition
| Emphysema and chronic bronchitis |
|
|
Term
irreversible component of COPD?
reversible components? |
|
Definition
Alveolar destruction is the main pathophysiological component (irreversible component)
Some patients have inflammation and bronchospasm (reversible components) |
|
|
Term
| Drug therapy is applicable to the ____ component of COPD |
|
Definition
|
|
Term
COPD treatment?
Inhaled _____ -> especially useful in patients with a vagally-mediated psychogenic component. (anxiety provoked)
Inhaled _____ -> As with asthma, continuous (overuse) of bronchodilators may be associated with worsening of symptoms. |
|
Definition
ipratropium bromide
B2-adrenergic agonists |
|
|
Term
| A subgroup of COPD patients may benefit from ____ therapy, but generally mixed results and not often used. |
|
Definition
|
|
