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820 > Chronic Asthma - Drugs > Flashcards

Chronic Asthma - Drugs Flashcards

1
Q

Asthma Controllers

A
  • ICS

- LABA

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2
Q

Asthma Add-Ons

A
  • Leukotriene modifiers
  • LAMA
  • OCS
  • Methylxanthines
  • Cromolyn
  • Biologics
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3
Q

Asthma Relievers

A
  • SABA
  • Anticholinergics
  • Systemic corticosteroids
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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
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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
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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
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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
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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
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9
Q

Beclomethasone HFA: 6-11 y.o. Dosing

A
  • Low Dose: 50-100 mcg
  • Medium Dose: >100-200 mcg
  • High Dose: >200 mcg
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10
Q

Budesonide DPI: 6-11 y.o. Dosing

A
  • Low Dose: 100-200 mcg
  • Medium Dose: >200-400 mcg
  • High Dose: >400 mcg
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11
Q

Budesonide Neb: 6-11 y.o. Dosing

A
  • Low Dose: 250-500 mcg
  • Medium Dose: >500-1000 mcg
  • High Dose: >1000 mcg
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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
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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
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14
Q

Beclomethasone HFA: >=12 y.o. Dosing

A
  • Low Dose: 100-200 mcg
  • Medium Dose: >200-400 mcg
  • High Dose: >400 mcg
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15
Q

Budesonide DPI: >= 12 y.o. Dosing

A
  • Low Dose: 200-400 mcg
  • Medium Dose: >400-800 mcg
  • High Dose: >800 mcg
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16
Q

Fluticasone Furoate DPI: >= 12 y.o. Dosing

A
  • Low Dose: 100 mcg

- High Dose: 200 mcg

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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
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18
Q

ICS Drug Interactions

A
  • Potent inhibitiors: CYP3A4

- Examples: Ritonavir, ketoconazole

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19
Q

ICS Local Effects

A
  • Oropharyngeal candidiasis
  • Dysphonia
  • Reflex cough and bronchospasm
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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
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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
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22
Q

ICS Low/Medium Doses + Children

A

NO AE on:

  • Bone mineral density
  • Subcapsular cataracts
  • Flaucoma
  • Clinically insignificant effects on HPA Axis
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23
Q

ICS + Bone Mineral Density

A
  • Suggests cumulative dose relationship in adults

- If there is a risk of osteoporosis, consider bone-protecting therapy

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24
Q

ICS + Ocular Effects

A
  • High cumulative lifetime exposure may increase prevalence of cataracts
  • Increase risk of glaucoma if family history
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25
Q

ICS + Dermal Thinning

A
  • Occurs with ICS, dose dependent

- Threshold dose is variable

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26
Q

ICS + Glucose Metabolism

A

Not clinically significant changes

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27
Q

Reducing ICS AE

A
  • Using holding chamber
  • Rinse month (rinse and spit)
  • Using lowest dose possible
  • Using in combo with LABA
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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)
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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

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