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Flashcards in Chronic Asthma - Drugs Deck (71):
1

Asthma Controllers

-ICS
-LABA

2

Asthma Add-Ons

-Leukotriene modifiers
-LAMA
-OCS
-Methylxanthines
-Cromolyn
-Biologics

3

Asthma Relievers

-SABA
-Anticholinergics
-Systemic corticosteroids

4

ICS

-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

ICS Beneficial Actions

-Increase the number of B2-adrenergic receptors, improving responsiveness to stimulation
-Reduce mucus production and hypersecretion
-Reduce airway edema

6

ICS + Daily Use Benefits

-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

ICS Response to Therapy

-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

Comparative Dosing of ICS

-Not equivalent
-Comparisons are estimated with few data to directly compare them
-Clinical judgement is the most important determinant of dosing

9

Beclomethasone HFA: 6-11 y.o. Dosing

-Low Dose: 50-100 mcg
-Medium Dose: >100-200 mcg
-High Dose: >200 mcg

10

Budesonide DPI: 6-11 y.o. Dosing

-Low Dose: 100-200 mcg
-Medium Dose: >200-400 mcg
-High Dose: >400 mcg

11

Budesonide Neb: 6-11 y.o. Dosing

-Low Dose: 250-500 mcg
-Medium Dose: >500-1000 mcg
-High Dose: >1000 mcg

12

Fluticasone Propionate HFA: 6-11 y.o. Dosing

-Low Dose: 100-200 mcg
-Medium Dose: >200-500 mcg
-High Dose: >500 mcg

13

Fluticasone Propionate DPI: 6-11 y.o. Dosing

-Low Dose: 100-200 mcg
-Medium Dose: >200-400 mcg
-High Dose: >400 mcg

14

Beclomethasone HFA: >=12 y.o. Dosing

-Low Dose: 100-200 mcg
-Medium Dose: >200-400 mcg
-High Dose: >400 mcg

15

Budesonide DPI: >= 12 y.o. Dosing

-Low Dose: 200-400 mcg
-Medium Dose: >400-800 mcg
-High Dose: >800 mcg

16

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

-Low Dose: 100 mcg
-High Dose: 200 mcg

17

Fluticasone Propionate HFA/DPI: >= 12 y.o. Dosing

-Low Dose: 100-250 mcg
-Medium Dose: >250-500 mcg
-High Dose: >500 mcg

18

ICS Drug Interactions

-Potent inhibitiors: CYP3A4
-Examples: Ritonavir, ketoconazole

19

ICS Local Effects

-Oropharyngeal candidiasis
-Dysphonia
-Reflex cough and bronchospasm

20

ICS Systemic Effects

-HPA Axis Suppression (most important)
-Impaired growth in children
-Decreased bone density
-Dermal thinning/bruising
-Cataracts/glaucoma
-Glucose metabolism
-Cushing's syndrome

21

ICS + Linear Growth in Children

-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

ICS Low/Medium Doses + Children

NO AE on:
-Bone mineral density
-Subcapsular cataracts
-Flaucoma
-Clinically insignificant effects on HPA Axis

23

ICS + Bone Mineral Density

-Suggests cumulative dose relationship in adults
-If there is a risk of osteoporosis, consider bone-protecting therapy

24

ICS + Ocular Effects

-High cumulative lifetime exposure may increase prevalence of cataracts
-Increase risk of glaucoma if family history

25

ICS + Dermal Thinning

-Occurs with ICS, dose dependent
-Threshold dose is variable

26

ICS + Glucose Metabolism

Not clinically significant changes

27

Reducing ICS AE

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

28

LABA

-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

LABA Max Doses

-Salmeterol: 100 mcg
-Formoterol: 24 mcg
-Vilanterol: 25 mcg

**Exceeding levels causes increased riskof asthma related deaths**

30

Mono-LABA for Asthma

-Serevent: Salmeterol
-DPI: 1 inhalation BID
-50 mcg/inhalation

31

LABA Interactions

-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

Montelukast

-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

Zafirlukast

-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

Zileuton

-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

Churg-Strauss-like Syndrome

-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

Neuropsychiatric Events + Singulair

-Possible association between behavior/mood changes, suicidality, and suicide
-Updated to be included in package inserts

37

Long-Acting Anticholinergic

-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

Menthylxanthines

-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

Menthylxanthines SE

-Nausea
-Irritability
-Insomnia
-Headache
-Vomiting
-Tachyarrhythmias
-Ventricular arrhythmias, seizures
**Minor SE do not always occur before life-threatening events**

40

Menthylxanthines Interactions

-Drug/Disease: Viral illness, CHF, cirrhosis, cigarette smoking, etc.
-Drug/Drug: cimetidine, macrolides, quinolones, CYP1A2 and CYP3A3

41

Cromolyn

-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

Xolair

-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

Nucala

-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

Cinqair

-Reslizumab
-Biologic
-Interleukin-5 antagonist
-Indication: add-on for severe asthma >= 18 y.o. with eosinophilic phenotype
-IV infusion q4w
-Box warning: anaphylaxis

45

Fasenra

-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

Dupixent

-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

Systemic Glucocorticoid Therapy

-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

Prednisone Dosing

-2 mg/kg/day
-Max: 60 mg/day
-Make repeated attempts to reduce dose and maintain control of symptoms

49

Quick Relief Medications

-SABA
-Anticholinergics
-Oral steroids

50

SABA

-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

SABA Examples

-Ventolin
-Proventil
-ProAir
-Xopenex (Levalbuterol)
-Metaproterenol

**Variety of dosage forms**

52

Chronic SABA Use

-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

Anticholinergics

-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

Oral Steroids

-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

Management Points

-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

School Children Special Considerations

-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

Older Adults Special Considerations

-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

Bronchodilator AE + Older Adults

-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

Theophylline AE + Older Adults

-CL is reduced, increased [blood]
-Potential for drug interactions

60

Corticosteroids AE + Older Adults

-Systemic CS can provoke confusion, agitation, changes in glucose metabolism
-ICS - dose-dependent reduction in bone mineral content

61

Pregnancy + Asthma

-Stepwise approach
-Budesonide = preferred ICS
-Albuterol = preferred rescue

62

EIB

-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

Managing EIB

-SABA used shortly before exercise
-Lengthy warm-up period before exercise may preclude medication
-Long-term control therapy, if appropriate

64

Alternatives Remedies

-No scientific basis for use
-Glucosamine-chondroitin sulfate may exacerbate asthma

65

OTC Products

-Primatene Tables - ephedrine/guaifenesin
-Primatene Mist - Epinephrine
-Asthmanefrin - Racepinephrine (use with EZ Breath Atomizer)

66

OTC + Pharmacist Role

-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

Drug-Induced Pulmonary Disease

-ASA/NSAIDs
-Inhaled Medications
-ACE Inhibitors
-Chemo Agents
-Amiodarone
-Beta-blockers

68

ASA/NSAID Bronchospasm

-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

ASA/NSAID Bronchospams PResentation

-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

ASA/NSAID Bronchospasm Management

-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

Inhaled Agents - Bronchospasm

-Nonspecific bronchial irritant effect
-Usually NOT caused by medication - propellant, delivery, pH, osmolality, temperature, preservative
-Albuterol, cromolyn, ICS, pentamidine, N-acetyl cysteine