Chronic Asthma - Drugs Flashcards
1
Q
Asthma Controllers
A
- ICS
- LABA
2
Q
Asthma Add-Ons
A
- Leukotriene modifiers
- LAMA
- OCS
- Methylxanthines
- Cromolyn
- Biologics
3
Q
Asthma Relievers
A
- SABA
- Anticholinergics
- Systemic corticosteroids
4
Q
ICS
A
- Most potent and effective anti-inflammatory available
- Small risk for adverse events at recommended doses
- Dose response curve is relatively flat, higher doses MAY reduce risk of exacerbations
5
Q
ICS Beneficial Actions
A
- Increase the number of B2-adrenergic receptors, improving responsiveness to stimulation
- Reduce mucus production and hypersecretion
- Reduce airway edema
6
Q
ICS + Daily Use Benefits
A
- Reduction in severity of symptoms
- Decreased BHR
- Prevention of exacerbations
- Reduced use of systemic corticosteroids
- Improved lung function
- Decreased ED care/hospitalizations
- Decreased deaths
7
Q
ICS Response to Therapy
A
- Symptoms improve in 1-2 weeks; max in 4-8 weeks
- FEV1 and peak expiratory flow require 3-6 weeks for max improvement
- BHR improvement in 2-3 weeks; max 1-3 months
8
Q
Comparative Dosing of ICS
A
- Not equivalent
- Comparisons are estimated with few data to directly compare them
- Clinical judgement is the most important determinant of dosing
9
Q
Beclomethasone HFA: 6-11 y.o. Dosing
A
- Low Dose: 50-100 mcg
- Medium Dose: >100-200 mcg
- High Dose: >200 mcg
10
Q
Budesonide DPI: 6-11 y.o. Dosing
A
- Low Dose: 100-200 mcg
- Medium Dose: >200-400 mcg
- High Dose: >400 mcg
11
Q
Budesonide Neb: 6-11 y.o. Dosing
A
- Low Dose: 250-500 mcg
- Medium Dose: >500-1000 mcg
- High Dose: >1000 mcg
12
Q
Fluticasone Propionate HFA: 6-11 y.o. Dosing
A
- Low Dose: 100-200 mcg
- Medium Dose: >200-500 mcg
- High Dose: >500 mcg
13
Q
Fluticasone Propionate DPI: 6-11 y.o. Dosing
A
- Low Dose: 100-200 mcg
- Medium Dose: >200-400 mcg
- High Dose: >400 mcg
14
Q
Beclomethasone HFA: >=12 y.o. Dosing
A
- Low Dose: 100-200 mcg
- Medium Dose: >200-400 mcg
- High Dose: >400 mcg
15
Q
Budesonide DPI: >= 12 y.o. Dosing
A
- Low Dose: 200-400 mcg
- Medium Dose: >400-800 mcg
- High Dose: >800 mcg
16
Q
Fluticasone Furoate DPI: >= 12 y.o. Dosing
A
- Low Dose: 100 mcg
- High Dose: 200 mcg
17
Q
Fluticasone Propionate HFA/DPI: >= 12 y.o. Dosing
A
- Low Dose: 100-250 mcg
- Medium Dose: >250-500 mcg
- High Dose: >500 mcg
18
Q
ICS Drug Interactions
A
- Potent inhibitiors: CYP3A4
- Examples: Ritonavir, ketoconazole
19
Q
ICS Local Effects
A
- Oropharyngeal candidiasis
- Dysphonia
- Reflex cough and bronchospasm
20
Q
ICS Systemic Effects
A
- HPA Axis Suppression (most important)
- Impaired growth in children
- Decreased bone density
- Dermal thinning/bruising
- Cataracts/glaucoma
- Glucose metabolism
- Cushing’s syndrome
21
Q
ICS + Linear Growth in Children
A
- Potential risks are well balanced by benefits
- Low to medium doses of ICS may have the potential of decreasing growth velocity but the effect is NOT sustained in subsequent years of treatment
- Cohort studies following children for more than 10 years suggest final height is attained
- Initial decrease in height persisted as a reduction in adult height
- Mean adult height was 1.2 cm lower in budesonide group compared to placebo
22
Q
ICS Low/Medium Doses + Children
A
NO AE on:
- Bone mineral density
- Subcapsular cataracts
- Flaucoma
- Clinically insignificant effects on HPA Axis
23
Q
ICS + Bone Mineral Density
A
- Suggests cumulative dose relationship in adults
- If there is a risk of osteoporosis, consider bone-protecting therapy
24
Q
ICS + Ocular Effects
A
- High cumulative lifetime exposure may increase prevalence of cataracts
- Increase risk of glaucoma if family history
25
Q
ICS + Dermal Thinning
A
- Occurs with ICS, dose dependent
- Threshold dose is variable
26
Q
ICS + Glucose Metabolism
A
Not clinically significant changes
27
Q
Reducing ICS AE
A
- Using holding chamber
- Rinse month (rinse and spit)
- Using lowest dose possible
- Using in combo with LABA
28
Q
LABA
A
- Not a substitute for anti-inflammatory therapy
- Not for monotherapy
- Beneficial with ICS
- Not for acute symptoms or exacerbations (at least 20 minutes onset)
- Tolerance with chronic admin
- Partial loss of protective effects of against methacholine, histamine, and exercise
- Bronchodilator response not decreased
- Responsiveness to SABA slightly decreased (increase dose by 1 puff)
29
Q
LABA Max Doses
A
- Salmeterol: 100 mcg
- Formoterol: 24 mcg
- Vilanterol: 25 mcg
Exceeding levels causes increased riskof asthma related deaths
30
Q
Mono-LABA for Asthma
A
- Serevent: Salmeterol
- DPI: 1 inhalation BID
- 50 mcg/inhalation
31
Q
LABA Interactions
A
- May increase the risk of CV AEs
- Use with CYP3A4 inhibitors increase salmeterol plasma levels
- Avoid: ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquiavir, telithromycin
- Causes: prolonged QTc intervals, palpitations, tachycardia
32
Q
Montelukast
A
- Singulair
- Leukotriene Modifier
- 4 mg QHS =<5 y.o.
- Options of oral granules or chewable tablets depending on age (can mix into food)
- 5 mg QHS - 6-14 y.o.
- 10 mg QHS >=15 y.o.
- Well tolerated: stomach pain, cough, headache are common SE
33
Q
Zafirlukast
A
- Accolate
- Leukotriene Modifier
- 10 mg BID (5-11 y.o.)
- 20 mg BID (>=12 y.o.)
- Liver toxicities - watch for signs of liver dysfunction/decline
- Interacts with Warfarin and increases prothrombin time by ~35%
- Food can reduce bioavailability - separate 1 hour before or 2 hours after meals
34
Q
Zileuton
A
- Zyflo CR
- 12 y.o.+
- 600 mg BID
- Within 1 hour after meals
- CI: active liver disease
- Monitor Liver Function: Serum ALT before treatment, monthly for first three months, every 2–3 months for remainder of first year, then periodically
- Interacts with theophylline (doubles []), warfarin (increases prothrombin time), and propranolol (doubles AUC)
35
Q
Churg-Strauss-like Syndrome
A
- Marked by circulating eosinophilia, heart failure, and eosinophilic vasculitis
- Rarely reported in patients receiving montelukast or zafirlukast
- Unclear cause
- Rare: 1 case in 15,000-20,000 patients
36
Q
Neuropsychiatric Events + Singulair
A
- Possible association between behavior/mood changes, suicidality, and suicide
- Updated to be included in package inserts
37
Q
Long-Acting Anticholinergic
A
- Spiriva Respimat
- Tiotropium Bromide
- 2 inhalations QD
- Add-on to ICS +/- LABA
- Approved for 6 y.o.+
- Caution: narrow-angle glaucoma, prostatic hyperplasia, bladder-neck obstruction
- Monitor for anticholinergic SE in those with moderate to severe renal function
38
Q
Menthylxanthines
A
- Monotherapy and adjuncive therapy with ICS
- NOT recc. for <4 y.o.
- Low therapeutic index
- Serum [] = 5-15 mcg/mL
- Therapy MUST be individualized to achieve optimal response and minimal SE
39
Q
Menthylxanthines SE
A
- Nausea
- Irritability
- Insomnia
- Headache
- Vomiting
- Tachyarrhythmias
- Ventricular arrhythmias, seizures
- *Minor SE do not always occur before life-threatening events**
40
Q
Menthylxanthines Interactions
A
- Drug/Disease: Viral illness, CHF, cirrhosis, cigarette smoking, etc.
- Drug/Drug: cimetidine, macrolides, quinolones, CYP1A2 and CYP3A3
41
Q
Cromolyn
A
- Alternative treatment for mild, persistent asthma
- Nebulizing solution
- 1 vial QID, may decrease to TID
- 4-6 weeks trial to determine max benefit
- Very safe
- Preventative treatment before exercise with SABA
42
Q
Xolair
A
- Omalizumab
- Biologic
- Humanized mAb against IgE
- Binds circulating IgE regarless of specificiity
- USed as adjunctive therapy in patients >= 12 y.o. who have allergies and SEVERE, persistent asthma
- Causes anaphylaxis in 0.1% - box warnings
- Specialty Pharmacy Tx
43
Q
Nucala
A
- Mepolizumab
- Biologic
- Interleukin-5 antagonist
- Indication: add-on maintenance for severe asthma in patients >= 12 y.o. with eosinophilic phenotype
- SQ injection - 100 mg q4w
- AE: headache, back pain, fatigue, injection site rxn
44
Q
Cinqair
A
- Reslizumab
- Biologic
- Interleukin-5 antagonist
- Indication: add-on for severe asthma >= 18 y.o. with eosinophilic phenotype
- IV infusion q4w
- Box warning: anaphylaxis
45
Q
Fasenra
A
- Benralizumab
- Biologic
- Interleukin-5 alpha-directed cytolytic monoclonal antibody
- Indication: severe asthma, >= 12 y.o., eosinophilic phenotype
- SQ injection q4w for 3 doses, then q8w
46
Q
Dupixent
A
- Dupilumab
- Biologic
- Interleukin-4 and interleukin-13 inhibitor
- Indication: add-on moderate-severe asthma, >= 12 y.o., eosinophilic phenotype OR OCS dependent asthma
- SQ qow
47
Q
Systemic Glucocorticoid Therapy
A
- Control chronic symptoms in people with severe asthma
- Use lowest dose possible
- Decrease toxicities by alternate day therapy
- Use inhaled steroids
- Tapering is necessary
- Shit ton of AEs
48
Q
Prednisone Dosing
A
- 2 mg/kg/day
- Max: 60 mg/day
- Make repeated attempts to reduce dose and maintain control of symptoms
49
Q
Quick Relief Medications
A
- SABA
- Anticholinergics
- Oral steroids
50
Q
SABA
A
- Most effective medication for relief of acute bronchospasm
- Using >2 days/week = inadequate control of asthma
- Regularly scheduled, daily, chronic use is NOT recommended
51
Q
SABA Examples
A
- Ventolin
- Proventil
- ProAir
- Xopenex (Levalbuterol)
- Metaproterenol
Variety of dosage forms
52
Q
Chronic SABA Use
A
- Does not improve control of symptoms
- Some patients get increases risk of exacerbations
- Some patients have decreased lung fxn - mechanism unclear but possibly due to a polymorphism in B2 receptor
53
Q
Anticholinergics
A
- Ipratropium (Atrovent)
- Indication: Relief of acute bronchospasm (NOT chronic therapy)
- Additive effects to B2 agonists in acute settings possibly
- Alt. for patients with B2 agonist intolerance
- Treatment of choice for bronchospasm due to Beta blockers
54
Q
Oral Steroids
A
- Used to treat asthma exacerbation
- Treatment of impending episodes of severe asthma unresponsive to bronchodilator therapy
- Outpatient: 1-2 mg/kg/day for 3-10 days, max of 60 mg/day
- Dose/duration depends on patient’s response and past history
- MUST taper
- TON of SE
- More than 3 courses per year => re-evaluate asthma management plan
55
Q
Management Points
A
- Goal = control asthma
- Initiating therapy: monitor 2-6 week intervals to ensure goal achieved
- Follow-up: regular follow-up at 1-6 mo. intervals depending on level of control
- Step-down therapy: good control has been achieved and maintained for 3 months, lung fxn reaches a plateau
56
Q
School Children Special Considerations
A
- Monitor growth in children receiving corticosteroids
- Encourage active participation in physical activity
- Provide written asthma management plan for school AND home
- Involve children in plan development
57
Q
Older Adults Special Considerations
A
- High prevalence of coexisting obstructive lung disease
- Asthma meds could aggravate preexisting conditions: cardiac disease, osteoporosis
- Aspirin and beta blockers could exacerbate asthma
- Essential to review patient technique with meds/devices
- Increased AE
58
Q
Bronchodilator AE + Older Adults
A
- Airway response to bronchodilators changes with age
- Patients with preexisting ischemic heart disease may experience a tremor and tachycardia
- Concomitant use of anticholinergics and beta2-agonists may be beneficial
59
Q
Theophylline AE + Older Adults
A
- CL is reduced, increased [blood]
- Potential for drug interactions
60
Q
Corticosteroids AE + Older Adults
A
- Systemic CS can provoke confusion, agitation, changes in glucose metabolism
- ICS - dose-dependent reduction in bone mineral content
61
Q
Pregnancy + Asthma
A
- Stepwise approach
- Budesonide = preferred ICS
- Albuterol = preferred rescue
62
Q
EIB
A
- Exercise-Induced Bronchospasm
- Anticipate with all patients
- Notify teachers and coaches
- Diagnosis: cough, SOB, chest pain/tightness, wheezing, or endurance problems during exercise
- Conduct exercise challenge or have patient undertake a task that evokes the symptoms
- 15% decrease in PEF or FEV1 = EIB compatible
63
Q
Managing EIB
A
- SABA used shortly before exercise
- Lengthy warm-up period before exercise may preclude medication
- Long-term control therapy, if appropriate
64
Q
Alternatives Remedies
A
- No scientific basis for use
- Glucosamine-chondroitin sulfate may exacerbate asthma
65
Q
OTC Products
A
- Primatene Tables - ephedrine/guaifenesin
- Primatene Mist - Epinephrine
- Asthmanefrin - Racepinephrine (use with EZ Breath Atomizer)
66
Q
OTC + Pharmacist Role
A
- Determine the pattern of use in those using OTC
- Self-treatment may delay necessary medical care which could result in resistant, acute, severe attacks
- If symptoms occur >1-2x per week OR nocturnal asthma ==> DOCTOR
67
Q
Drug-Induced Pulmonary Disease
A
- ASA/NSAIDs
- Inhaled Medications
- ACE Inhibitors
- Chemo Agents
- Amiodarone
- Beta-blockers
68
Q
ASA/NSAID Bronchospasm
A
- AERD
- Prevalence: <5% in those with asthma
- Up to 40% in those with asthma and chronic rhinosinusitis with nasal polyps (Samter’s Triad)
- Usually diagnosed in adulthood
- Develops over years - ASA sensitivity appears during progression
69
Q
ASA/NSAID Bronchospams PResentation
A
- Minutes to hours after ingestion
- Nasal/ocular symptoms: congestion, rhinorrhea, conjuctivitis, periorbital edema
- Asthma symptoms
- Abdominal cramps
- Epigastric pain
- Hypotension
- Can be separate or blended
70
Q
ASA/NSAID Bronchospasm Management
A
- Avoid ASA/COX-1 inhibiting NSAIDS
- Desensitization and continuous aspirin therapy by slowing increasing doses of oral aspirin
- Use Tylenol or COX-2 selective NSAIDs
71
Q
Inhaled Agents - Bronchospasm
A
- Nonspecific bronchial irritant effect
- Usually NOT caused by medication - propellant, delivery, pH, osmolality, temperature, preservative
- Albuterol, cromolyn, ICS, pentamidine, N-acetyl cysteine
