Transcript COPD - UW Canvas

Asthma, COPD,
Allergic Rhinitis
Cough, Colds
Drugs for Respiratory Conditions:
Chronic Obstructive Pulmonary Diseases (COPD)Asthma, Emphysema, Chronic Bronchitis
Acute illnesses- Allergic Rhinitis, Cough & Colds
What is COPD?
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COPD — The Global Initiative for Chronic Obstructive
Lung Disease (GOLD), a project initiated by the
National Heart, Lung, and Blood Institute (NHLBI) and
the World Health Organization (WHO), defines COPD
as follows:
"Chronic obstructive pulmonary disease (COPD), a
common preventable and treatable disease, is
characterized by airflow limitation that is usually
progressive and associated with an enhanced chronic
inflammatory response in the airways and the lung to
noxious particles or gases. Exacerbations and
comorbidities contribute to the overall severity in
individual patients."
Chronic Obstructive Pulmonary Disease
EMPHYSEMA
Chronic obstructive
ASTHMA
CHRONIC BRONCHITIS
“Subtypes” of COPD; pts often have some degree of overlap in these diseases
Asthma
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Chronic, obstructive airway disease
Causes:
• Reversible hyperreactivity of bronchi &
bronchioles
• Bronchoconstriction
• Vasodilation
• Edema
• Mucous production
• Progressive airway remodeling over
time
Asthma symptoms
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Cough, including at night
Wheezing
Chest tightness
Shortness of breath
Mucus plugging
Pathophysiology
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Allergens bind to IgE antibodies on mast cells
Mast cells release inflammatory mediators
(e.g., histamines, leukotrienes,
prostaglandins)
Mediators cause inflammatory cells (e.g.,
eosinophils, leukocytes) to infiltrate airway
walls, releasing more inflammatory mediators
End result: airway inflammation and edema,
increased mucus, smooth muscle hypertrophy,
bronchospasm, “ramped up” airway hyperreactivity
Anti IgE
Leukotriene
modifiers
Glucocorticoids
Processs of Bronchoconstriction and
Drugs used to DILATE the BRONCHI
Cromolyn
Processs of Inflammation and
Drugs used to treat inflammation
Asthma episodes are characterized by Inflammation and Bronchoconstriction
BOTH of these problems need to be treated
AntiCholinergic
Beta 2
agonists
Methylxanthines
Asthma Treatment
Expert Panel Report 3 (EPR-3)
4 Components:
 Assessment & Monitoring
 Education
 Control of environmental factors
 Medications
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
COPD
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Chronic bronchitis – excessive
mucous secretion in the bronchial
tree
• cough, sputum, & airflow obstruction
• involves bronchospasm
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Emphysema – distended,
hyperinflated, less elastic alveoli
• Air trapping
Global strategy for diagnosis, management, & treatment
of Obstructive Lung Disease (GOLD Criteria)
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“Pulmonary Function Tests” (PFTs) are used to
evaluate lung function:
• diagnose and stage disease
• Monitor efficacy of treatment or progression of
disease
 FEV1
Staging determines treatment strategy
• Stage 1 – Mild
• Stage 2 – Moderate
• Stage 3 – Severe
• Stage 4 – Very severe
Treatment: Control Symptoms
COPD Treatments…
 do not reduce mortality
 do reduce symptoms and improve
QoL
Medications – Asthma & COPD
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Address BOTH bronchoconstriction &
inflammation
Bronchodilators
• beta2 agonists
• methylxanthines
• anticholinergics
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Anti-inflammatory
• glucocorticoids
(steroids)
• cromolyn
• leukotriene
modifiers
• IgE blockers
Quick relief vs Long-Term
Quick
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Short acting beta
agonist (SABA)
Long-term
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Anticholinergics
IV & oral
glucocorticoids
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Long acting beta
agonists (LABA)
Methylxanthines
Inhaled GCs
Cromolyn
Anti-IgE
Leukitriene
modifiers
Medication Routes
Route
Medication
Inhaled
MDI – aerosol
MDI - powder
Nebulizer
Beta-2 agonists (short &
long acting)
Anticholinergics
Glucocorticoids
Oral
Methylxantines
Leukotriene modulators
Injection
Glucocorticoids
Beta-2 agonists
Inhalation Drug Therapy
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Three obvious advantages
• Therapeutic effects are enhanced
• Systemic effects are minimized
• Relief of acute attacks is rapid (SABA)
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Three types
• Metered-dose inhalers (MDIs)
• Dry-powder inhalers (DPIs)
• Nebulizers
Types of inhalation devices
metered-dose inhalers (MDIs)
dry-powder inhalers (DPIs)
Require strong inhale
metered-dose inhaler
plus SPACER
Eg AEROCHAMBER
Nebulizersmask or inhaler
Use of a “spacer” (eg Aerochamber) greatly improves
appropriate delivery of the medication,
and therefore efficacy of drug therapy
Factors affecting efficacy
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Inhaled medications:
• Particle size
• Specific equipment use
• Delivery technique
• RECOMMEND: read package insert!
Proper Inhaler Technique
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10-25% of expelled medication will reach
pulmonary system
• Remainder is deposited on the mouth,
pharynx, esophagus, and stomach
40% of persons are NOT able
to demonstrate proper
inhaler technique
Proper Inhaler Technique
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Majority of medication accumulates on the
throat and contributes to systemic side effects
• Rinse mouth after ICS
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Use of proper technique or Aerochamber
improves lung deposition and reduces
systemic side effects
• Aerochamber improves lung deposition by
25%
Spacer vs Suspending
Chamber
Proper Metered Dose Inhaler
(MDI) Technique
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When using MDI for first time:
• Shake the inhaler for 60 seconds
• Prime the inhaler by pressing down the
canister with the index finger to release the
medication
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Press canister down again 2-3 times
 After an inhaler is used for the first time, no
need to prime again UNLESS patient has not
used for 2 weeks or more
Proper MDI Technique
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Shake canister vigorously for 60 seconds
Uncap mouthpiece and check for loose objects in the device
Breathe out normally
Hold MDI upright
Close lips around spacer OR if no spacer is available, close
lips around mouthpiece or position it about 4 cm from the
mouth
• Keep tongue away from the spacer opening or
mouthpiece
Exhale completely before MDI actuation
Slow deep inhalation (3-5 sec) until the lungs are completely
filled
Press down the top of the medication canister with the index
finger to release the medication
MDI Inhaler Technique Pearls
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One puff per inhalation
Wait 5 minutes between puffs, or long
enough to perform the next inhalation
properly
Shake canister again before use
Recap mouthpiece
Rinse mouth after using an ICS, and
spit the water out rather than
swallow it
Bronchodilators for asthma:
beta2-adrenergic agonists
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Sympathomimetic drugs: activate beta2adrenergic receptors
• Located where?
• What effect?
Inhaled and oral
Inhaled:
• nebulized, MDI, or dry powder
• can be used as “rescue meds” or for
prevention/control
Bronchodilators for asthma
Beta2-adrenergic agonists
• inhaled, short-acting (SABA)
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albuterol, bitolterol, levalbuterol, pirbuterol
• inhaled, long acting (LABA)
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salmeterol, formoterol
• Oral, long acting
albuterol, terbutaline
SIDE EFFECTS: All the Beta2- adrenergic agonists also
have some effect on beta1 receptors
 SE = ↑HR, tremors, chest pain
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Bronchodilators for asthma:
Anticholinergics
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Ipratropium (Atrovent)
• SHORT-ACTING: PK
• promotes bronchodilation by blocking
cholinergic receptors in airways smooth
muscle relaxation
• additive effects when used with beta2-agonists
• MDI or nebulizer
• Indications: COPD, (asthma)
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Tiotropium (Spiriva)
• Long-acting anticholinergic: PK
• Recently approved for use in COPD
• Advantages over ipratripium
Inhalers that combine more than one medication
• Ipratropium PLUS Albuterol (“Combivent”)
‒ combines a short-acting anticholinergic
PLUS short acting beta 2 agonist
• Used by many people
• Cannot be used if peanut allergy due to specific
way that this product is manufactured
− People with peanut allergy can use
ipratropium and albuterol separately, but not
in this combined product
Bronchodilators for asthma:
Methylxanthines
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Theophylline
• Highly variable oral absorption
• Multiple drug interactions
• Toxicity can be fatal
• Plasma levels must be monitored
• Sustained release preparations
preferred
Aminophylline
• Preferred form for IV use
• Loading dose; slow infusion
• Rectal preparations also available
Anti-inflammatory Drugs
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Glucocorticoids
• inhaled, IV, and oral
• decrease inflammation, airway edema,
mucus production
• increase responsiveness to beta2
agonists
• chronic inhaled: first-line therapy for
moderate to severe asthma
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maintain control, NOT abort acute attacks
Inhaled Glucocorticoids:
drugs and doses
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Inhaled-MDI or dry-powder
• beclomethasone, budesonide,
flunisolide, fluticasone, triamcinolone
Usual dose: 1-2 puffs 2-4 times per day
MDIs-use a spacer
All types - rinse mouth after use
Possible SE: adrenal suppression, bone
loss
When used together which is first glucocorticoid or bronchodilator?
Systemic glucocorticoids for
asthma
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Oral: prednisone or prednisolone
• Short-term therapy for acute exacerbations;
chronic use if unable to control symptoms
otherwise
• Goal: once daily or QOD dosing, early
afternoon
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Consider IgE blockers if remains poorly
controlled
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IV: for acute attack needing emergency
care, admission
Systemic glucocorticoids for
asthma
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Systemic steroids (IV or oral) used
in high-dose, short-term “pulses” to
control acute exacerbations
What are the adverse effects of
chronic systemic steroid use?
Anti-inflammatory drugs for asthma
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Cromolyn
• stabilizes mast cells reduced release
of mediators
• inhibits proliferation of inflammatory
cells
• nebulized or MDI
• first line drug for control of asthma
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NOT effective in acute attacks
Anti-inflammatory drugs for
asthma: Leukotriene Modifiers
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Decrease eosinophil infiltration, mucus
production, airway edema,
bronchoconstriction
Oral administration
Prophylaxis/maintenance
Zileuton (Zyflo), Zafirlukast (Accolate),
Montelukast (Singulair)
Singulair may be preferred because . . . .
Anti-inflammatory drugs for
asthma: IgE Blockers
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Omalizumab—Xolair
Binds circulating IgE
Inhibits binding of IgE to mast cells,
preventing release of inflammatory
mediators
Down-regulates mast cell receptors for IgE
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Drawbacks to use . . .
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Asthma Guidelines – EPR-3
Pattern
Treatment
Mild intermittent
SABA PRN
Mild persistent
Low dose inhaled GC & SABA PRN
Moderate persistent
Inhaled GC and LABA OR inhaled GC
and leukotriene
modifier/methylxanthine
SABA PRN
Severe persistent
Medium to high dose inhaled GC with
LABA plus other meds (leukotriene
modifier/methylxanthine/anti-IgE)
May need short course oral GC
SABA PRN
GOLD GUIDELINES
CATEGORY
SYMPTOMS
THERAPY
A (mild/
moderate)
Less
Short-acting bronchodilator
- SABA
- Anticholinergic
B (mild/
moderate)
More
Add to short acting
- LABA or
- Anticholinergic
C (severe/ very
severe)
Less
Inhaled GC + LABA or
Long acting anticholinergic
D (severe/ very
severe)
More
Inhaled GC + LABA and/or
Long acting anticholinergic
Management of asthma:
Acute exacerbation
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Inhaled beta2 agonists for acute relief of
bronchospasm (MDI with spacer or
nebulized solution)
IV or oral steroid therapy
Supplemental oxygen to keep O2 sats >
95%
SQ epinephrine if unable to use inhaled
May require hospitalization
Allergic Rhinitis, Cough and Colds
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Allergic rhinitis-inflammation of the
nasal mucosa in response to
allergens
Seasonal or perennial
Sneezing, runny nose, itching, nasal
congestion due to release of
histamine and inflammatory
mediators
Variety of drugs are used to treat
allergic rhinitis
Antihistamines
• Oral; intranasal
Intranasal glucocorticoids
Intranasal cromolyn
Sympathomimetics (decongestants)
• Oral; topical
Anticholinergics
Subcutaneous omalizumab
Antihistamines (H1 antagonist)*
Therapeutic uses
 Relieve allergic reactions
 Motion sickness (Dramamine)
 Sleep aid
 Common cold (for anticholinergic
effects)
*H2 antagonists – reduce stomach acid
(famotidine, ranitidine)
Antihistamines – Side effects
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Sedation
Paradoxical stimulation (esp. in
young & old)
GI symptoms (N/V/D or constipation)
Anticholinergic
• Dry mouth
• Palpitations
• Urinary retention
• Confusion
Antihistamine meds
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First generation
• Diphenhydramine (Benadryl),
chlorpheniramine (Chlor Trimeton),
doxylamine (Unisom)
Second generation
• fexofenadine (Allegra),
cetirizine (Zyrtec),
loratidine (Claritin)
• “non-sedating” (don’t cross BBB well)
• Some differences in metabolism & excretion
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Nasal spray: azelastine (Astelin)
Antihistamines
Class
1st Generation
2nd Generation
Alkylamines
Brompheniramine
Chlorpheniramine
Pheniramine
Triprolidine
Acrivastine
Ethanolamines
Clemastine (Tavist)
Diphenhydramine (Benadryl)
Doxylamine
Piperazines
Hydroxyzine (Vistaril)
Meclizine (Bonine, Antivert)
Cetirizine (Zyrtec)
Levocetirizine (Xyzal)
Piperidine
Azatadine
Cyproheptadine
Astemizole
Loratadine (Claritin)
Desloratadine (Clarinex)
Phenothiazines
Promethazine
Fexofenadine (Allegra)
Olopatadine
Terfenadine
Other
Doxepin
Azelastine
Emedastine
How long do Antihistamines
take to work?
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1st Generation
 Onset of effect: 15-60 minutes
 Duration of effect: 4-8 hours
 Half-life: 3-8 hours
2nd Generation
 Onset of effect: 1-3 hours
 Duration of effect: 12-24 hours
 Half-life: 12-15 hours
Intranasal glucocorticoids
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Also first line therapy; most effective
drugs for prevention & treatment of
allergic rhinitis
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Beneficial effects take 2 to 3 weeks
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Pre-treat with nasal decongestant
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SE: nasal dryness, burning; potential
for systemic absorption
Dose: start with full dose then reduce
when symptoms are under control
Intranasal Cromolyn
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Less effective than intranasal
glucocorticoids
Takes 2 – 3 weeks to establish
benefit
Continue use even if symptom-free
Pre-treat with decongestant
Dose: one spray 3 to 6 times daily
Decongestants
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Sympathomimetics:
• stimulate alpha1 receptors on blood vessels
in nose  resulting in . . . .
Only relieve stuffiness; not helpful for allergy
symptoms
Oral agents:
• e.g. Sudafed, Neo-synephrine
• CNS stimulation; abuse potential
Topical: Afrin – rebound congestion
Avoid phenylpropanolamine
Combination therapies to treat
allergic rhinitis
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Combination therapies are useful –
antihistamines & sympathomimetics
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Examples - Allegra-D; Claritin-D
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Can also use:
• Anticholinergic
• Leukotrine modifiers
• Omalizumab
Drugs for Cough
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Antitussives
• opioid
• non-opioid
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Dextromethorphan
Expectorants
• guaifenesin
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Mucolytics
• mucomyst
Cold Remedies
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Acute upper respiratory viral infection
Multiple symptoms
Multiple cold remedies—
• usually combination preparations
• choose a preparation that covers only the
symptoms that need to be addressed
• avoid phenylpropanolamine
Factors affecting adherence
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Frequency of administration
Difficulty of administration
Side effects
Cost / coverage for drug
Perceived benefit of drug