Bronchodilators, Corticosteroids, and the Pharmacotherapy of Asthma and COPD Flashcards
(87 cards)
1
Q
Short-acting bagonists (SABA)
list
A
*Albuterol, others
2
Q
Long-acting bagonists (LABA)
list
A
Salmeterol, formoterol
3
Q
Emergency, non-selective bagonist
list
A
Epinephrine*
4
Q
Muscarinic Antagonists
list
A
Ipratropium, tiotropium
5
Q
Methylxanthine
list
A
Theophylline*
6
Q
Inhaled Corticosteroids (ICS)
list
A
Beclomethasone Budesonide Ciclesonide Flunisolide Fluticasone Mometasone Triamcinolone
7
Q
Oral Corticosteroids
list
A
Methylprednisolone
Prednisone
8
Q
Leukotriene Receptor Antagonist (LTRA)
list
A
Montelukast
Zafirlukast
9
Q
Cromolyn compounds
list
A
Cromolyn sodium
10
Q
Anti-IgE Antibody
list
A
Omalizumab
11
Q
Bronchospasm
A
In allergic asthmatics patients, immediate hypersensitivity-type reactions can be continuously present at a sub-threshold level, resulting in mild-to-moderate inflammation without overt bronchoconstriction.
12
Q
Overt bronchospasm*
A
then occurs upon exposure to a specific allergen or to a variety of nonspecific stimuli, e.g., cold air, dust, air pollution, exercise, etc.
13
Q
Inflammatory Mediators in Asthma
A
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.
Corticosteroids, which are capable of blocking many key steps in the inflammatory process, come closest to this ideal therapy
14
Q
Mast Cell Mediators of Inflammatory Processes
preformed (immediate)
A
mediator - histamine tnfa proteases heparin
effects - bronchoconstriction itch cough vasodilation edema
15
Q
Mast Cell Mediators of Inflammatory Processes
lipids (minutes)
A
mediator - leukotrienes prostaglandins
effects - bronchoconstriction chemotaxis mucus secretion
16
Q
Mast Cell Mediators of Inflammatory Processes
cytokines (hours)
A
mediator - interleukins GM-CSF
effects - bronchoconstriction, chemotaxis inflammatory cell proliferation
17
Q
Aerosol Delivery of Drugs
A
Particle size of aerosol is important.
Rate of breathing and breath holding.
Even under ideal conditions, 90% of inhaled drug is swallowed.
Therefore, ideally the best drugs also have poor absoption from the GI tract and/or rapid first-pass metabolism in the liver.
18
Q
Classification of asthma
intermittent
A
Symptoms - 80%, fev1/fvc normal
19
Q
Classification of asthma
mild
A
Symptoms - > days /week but not daily
nighttime awakenings - 3-4Xmonth
short acting beta2 agonist use for symptom control - >2daysa week but no >1 a day
interference with normal activity - minor limitation
lung function - fev1>80% predicted, fev1/fvc normal
20
Q
Classification of asthma
moderate
A
Symptoms - daily
nighttime awakenings - >1 time a week but not nightly
short acting beta2 agonist use for symptom control - daily
interference with normal activity - some limitation
lung function - fev1>60% predicted but less than80%, fev1/fvx reduced 5%
21
Q
Classification of asthma
severe
A
Symptoms - throughout the day
nighttime awakenings - often nightly
short acting beta2 agonist use for symptom control - several times per day
interference with normal activity - extremely inhibited
lung function - fev15%
22
Q
Stepwise approach for managing asthma adults
step 1
A
preferred
sabaprn
23
Q
Stepwise approach for managing asthma adults
step 2
A
preferred
low dose ICS
alternative
cromolyn ltra nedocromil or theophyllin
24
Q
Stepwise approach for managing asthma adults
step 3
A
preferred
low does ICS and laba or medium dose ICS
alternative
low dose ICS and either ltra theophylline or zileudon
25
Stepwise approach for managing asthma adults
step 4
preferred
medium dose ics and laba
alternative
medium dose ics and either ltra theophylline or zileuton
26
Stepwise approach for managing asthma adults
step 5
preferred high dose Ics and laba and consider omalizumab for patients who have allergies
27
Stepwise approach for managing asthma adults
step 6
preferred
high dose ics and laba and oral corticosteroid and consider omalizumab for pts who have allergies
28
intermittent asthma treatment
saba as needed
29
mild persistent asthma treaments
preferred - low dose ics
alternatives - montelukast or theophylline
30
moderate persistent asthma treatments
preffered - low dose ics and a laba or medium dose ics
alternatives - low dose ics and a leukotriene modifier or theophyllin
31
severe persistent asthma treatments
preferred - medium or high dose ics and a laba
alternatives - medium dose ics and a leukotrient modifier or theophylline
32
asthma treatment ages 5-11
step 1
preferred - saba prn
33
asthma treatment ages 5-11
step 2
preferred - low dose ics
alternative - cromolyn, ltra, nedocromil, or theophyllin
34
asthma treatment ages 5-11
step 3
preferred - lowe dose ics and either laba ltra or theophylline
or
medium dose ics
35
asthma treatment ages 5-11
step 4
preferred - medium dose ics and laba
alternative - medium dose ics and etiher ltra or theophylline
36
asthma treatment ages 5-11
step 5
preferred - high dose ics and laba
alternative - high dose ics and either ltra or theophyllin
37
asthma treatment ages 5-11
step 6
preferred - high dose ics and laba and oral systemic corticosteroid
alternative - high dose ics and either ltra or theophylline and oral systemic corticosteroid
38
b-Adrenergic Agonists
Therapeutic Use in Asthma and COPD
Drug of choice for rapid relief of bronchospasm
| Highly effective and safe for intermittent, prophylactic treatment of asthma.
39
b-Adrenergic Agonists
Current Emphasis
Intermittent use on an as-needed basis for relief of acute, severe bronchospasm. Not general prophylaxis.
40
b-Adrenergic Agonists
Overuse:
Side effects intensify will 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.
41
b-Adrenergic Agonists
Mechanism of Action:
Stimulate b2-adrenergic receptor on surface of bronchiolar smooth muscle cells.
b2-adrenergic receptor couples to Gs protein and activates adenylyl cyclase enzyme leading to increased cellular levels of cyclicAMP.
Cyclic AMP stimulates phosphorylation cascade that leads to decreased intracellular calcium and smooth muscle relaxation.
Also inhibit mediator release from mast cells.
42
b-Adrenergic Agonists
Rapid Acting-Short Duration
Albuterolonset
43
Long Actingb2-Selective Agonists (LABA
salmeterol:
slower onset
duration > 12 hours of useful bronchodilation
useful to control nighttime asthma attacks, also now used BID for prevention
not suitable for treatment of acute bronchospastic attacks because onset of action is too slow.
Formoterol
Similar to salmeterol
Not for acute attacks
44
Less Selective or Nonselective b-Adrenergic Agonists
Epinephrine
Isoproterenol
Metaproterenol
Isoetharine
Because of their very short duration of action and their lack of b2-selectivity, these agents are not frequently used.
Low-strength epinephrine inhalers sometimes prescribed for mild asthma
Racemic Epinephrine
aerosol used for pediatric patients
45
Long-term Use of LABA
Continued use of a LABA may cause down-regulation of b2 receptors with loss of the protective effect from rescue therapy with a short-acting agent.
LABA should not be used for monotherapy in patients with persistent asthma, especially in children.
LABA should be used in asthma only in combination with an inhaled corticosteroid.
“Stop use of a LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid”.
46
Oral Therapy withb-Adrenergic Agonists
| Oral administration increases incidence of adverse side effects:
muscle tremor, cramps, cardiac tachyarrhythmias, metabolic disturbances, hypokalemia
47
Oral Therapy withb-Adrenergic Agonists
Appropriate situations for oral therapy
brief therapy in children with upper respiratory tract infections who cannot manipulate inhaler
in severe asthma exacerbations where inhaler cannot be used or when aerosol is irritating
oral albuterol and terbutaline are available
48
Adverse Side Effects ofb-Adrenergic Agonists
Patients with cardiovasculardisease or diabetesare at higher risk of adverse effects.
Skeletal muscle tremor (most frequent side effect)
CNS: restlessness, apprehension, anxiety, tremors
CVS: tachycardia, dysrhythmias, hyper-or hypotension
hypokalemia
worsen hyperglycemia in diabetics
drug interactions with thyroid, digitalis, methylxanthines
49
Epinephrine: Emergency Use
Epinephrine is the drug of choice for treatment of anaphylactic reactions.
Give SQ (or IM or IV with dextrose)
Bronchodilation (mediated by b2receptors)
Vasoconstriction (mediated by 1receptors)
maintains BP & decreases edema
Inhibition of mediator release (b2receptors)
50
Anaphylaxis Treatments
```
Albuterol via nebulizer
IV fluids
Oxygen
Secondary therapy
H1 antagonist -diphenhydramine
H2 antagonist -ranitidine
Corticosteroid -hydrocortisone, methylprednisolone
Aminophylline
NE, glucagon -for hypotension
```
51
Bronchodilators:Ipratropium bromide OVERVIEW
A quaternary muscarinic receptor antagonist
If given parenterally, effects are like atropine
But, only given as inhaled aerosol
few side effects, even when swallowed because is poorly absorbed from GI and does not cross into brain
quaternary amine-poor diffusion across membranes
52
Bronchodilators:Ipratropium bromide
parasympathetic
mediated bronchospasm is a significant component of airway resistance in some asthmatics and COPD patients, especially psychogenic exacerbations
53
Ipratropium bromide
| Therapeutic Use:
Bronchodilation develops more slowly and is usually less intense than that produced by b-agonists.
Useful bronchodilationlasts up to 6 hours.
Principal use of ipratropium is in COPD.
Combined with albuterol = COMBIVENT
Also used intranasally to reduce secretions in the upper and lower respiratory tract in allergic rhinitisand chronic postnasal drip syndrome
54
Tiotropium
newer long-acting agent (QD dosing) used for maintenance therapy in chronic bronchitis and emphysema; dry powder inhaler device
55
Methylxanthines
drugs
theophylline, caffeine, theobromine
| found in coffee, tea, chocolate, cocoa, colas
56
Methylxanthines
| Diverse cellular actions
adenosine receptor antagonists
block cyclic AMP degradation –PDE inhibitor
lower intracellular calcium
hyperpolarize cell membranes
57
Theophylline
Bronchodilationis a clinically relevant effect of theophylline
Other effects include CNS stimulation, modest peripheral vasodilation, improved skeletal muscle contractility, and a thiazide-like diuresis
58
Theophylline
| Therapeutic Use:
Formerlya first-line agent for treatment of asthma
Nowhas a far less prominent role because:
benefits are modest
narrow therapeutic window
considerable variation in absorption and elimination between different patients
monitoring of plasma concentrations is often required
59
Theophylline
Nocturnal asthma
can be improved with slow-release theophylline, but inhaled corticosteroids and salmeterol are probably more effective.
IV formulation = aminophylline
60
Anti-Inflammatory AgentsCorticosteroids
overview
In asthma (and some COPD) an inflammatory responseis responsible for the underlying disease process.
So many inflammatory mediators are involved that a blocker of any given autocoid or cytokine, e.g., antihistamine, is ineffective in alleviating the symptoms of asthma.
Corticosteroids block many of the steps involved in the inflammatory cascade.
61
Anti-Inflammatory AgentsCorticosteroids
| Mechanism of Action
corticosteroids are steroid receptor agonists that bind to intracellular receptors that translocate to the cell nucleus and positively or negatively regulate gene transcription. This takes time.
corticosteroids inhibit the production and release of cytokines, vasoactive and chemoattractivefactors, lipolytic and proteolytic enzymes, decrease mobilization of leukocytes to areas of injury, and decrease fibrosis.
General anti-inflammatory response
62
Inhaled Corticosteroids
```
Beclomethasone dipropionate (Beclovent)
Budesonide dipropionate (Pulmicort)
Ciclesonide (Alvesco)
Flunisolide (AeroBid)
Fluticasone (Flovent)
Mometasone (Asmanex Twisthaler)
Triamcinolone acetonide (Azmacort)
```
63
Systemic Corticosteroids
| IV or oral
Prednisone
Methylprednisolone
Hydrocortisone
64
Corticosteroids overview asthma
Corticosteroids have potentially important adverse side effects.
Aerosol delivery of the steroid has significantly improved the safety of treatment for moderate to severe asthma.
Asthmatics who require inhaled b-adrenergic agonist therapy 3 -4 or more times weekly are candidates for inhaled steroid therapy.
65
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.
66
Corticosteroids
| Asthmatic patients maintained on inhaled
corticosteroids show improvement of symptoms and lower requirements for “rescue” with a bronchodilator.
67
Corticosteroids
| Systemic Therapy
Systemic (i.v. or oral) steroid therapy is used in severe asthmatic attacks requiring hospitalization.
For severe asthma, prednisoneor methylprednisoloneis given i.v., followed by oral doses and gradual tapering of the dose.
For acute, sever exacerbations, oral prednisone is administered for 1 -2 weeks.
Longer treatments require tapering of the dose to account for hypothalamic-pituitary-adrenal suppression.
68
Corticosteroids:Potential Side Effects
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
Dysphonia -usually resolves
Candidiasis -use spacer device and rinse mouth
Growth retardation -of concern in children
69
Combination Products
Fluticasone propionate +Salmeterol (Advair Diskus, Advair HFA)
Budesonide + Formoterol(Symbicort HFA)
Mometasone + Formoterol (Dulera)
Not useful for acutebronchospastic attack
Cost Range: ~$145-$175/month
70
Chronic Obstructive Pulmonary Disease (COPD)
Emphysema and chronic bronchitis
Smoking cessation
Alveolar destruction is the main pathophysiological component (irreversible component)
Some patients have inflammation and bronchospasm (reversible components)
Drug therapy is applicable to the reversible component of COPD
71
COPD Treatment
Group A
preferred - short acting anticholinergic prn or saba prn
aleternative - long acting anticholinergic or laba or saba and short ancting anticholinergic
72
COPD Treatment
Group B
preferred - long acting anticholinergic or laba
alternative - long acting anticholinergic and laba
73
COPD Treatment
Group C
preferred - ics and laba or long acting anticholinergic
alternative long acting anticholinrgic and laba or ics, or pde4 inhibitor and long acting anticholinergic or laba
74
COPD Treatment
Group D
preferred - ics and laba and/or long acting anticholinergic
alternative - ics and laba and long acting anticholinergic or ics and laba and pde4 inhibitor or long acting anticholinergic and laba or long acting anticholinergic and pde4 inhibitor
75
Chronic Obstructive Pulmonary Disease (COPD)
Inhaled ipratropium bromide or tiotropium
especially useful in patients with a vagally-mediated psychogenic component
76
Chronic Obstructive Pulmonary Disease (COPD)
Inhaled b2-adrenergic agonists
As with asthma, continuous (overuse) of bronchodilators may be associated with worsening of symptoms
77
Chronic Obstructive Pulmonary Disease (COPD)
A subgroup of COPD patients
may benefit from corticosteroid therapy, but generally mixed results of steroids in COPD.
78
Cromolyn Compounds
Cromolyn sodium (Intal)
Cromolyn sodium is an anti-inflammatoryagent that indirectly inhibits antigen-induced bronchospasm and directly inhibits the release of histamine and other autocoids from sensitized mast cells.
May suppress the activating effects of chemoattractant peptides on eosinophils, neutrophils, and monocytes.
79
Cromolyn Compounds:Therapeutic Use
Cromolyn compounds do not directly relax smooth muscle, therefore they are not useful for control of acute bronchospasm.
Cromolyn compounds are primarily prophylactic. When inhaled several times daily, they inhibit both the immediate and late asthmatic responses to antigenic challenge or exercise.
80
Leukotriene inhibitors
Zafirlukast
LTD4 receptor antagonist
Montelukast
LTD4 receptor antagonist
Alternative or adjunctive therapy to low-dose corticosteroids for mild persistent asthma.
Useful as oral prophylaxis in exercise-induced asthma.
81
muscarinic antagonists are used mainly for
copd
82
ltras are less effective but
less side effects
83
theophylline increases
dynamic contraction of diaphragm
84
theophylline is not used bc
too many side effects and have to monitor too much
85
corticosteroids pic
croticosteroids related to cortisol
affect glucose metabolism
hypdrophobic and cross into cell bind to recptr in cell forms a dimer attaches to dna and transcritipon to shutdown of it takes place
86
CORTICOSTEROIDS ARE DANGEROUS WHEN
LONG term use
low dose are ok
87
once you destroy the alveoli
there is no way to really fix that
