an initiative of - calrightmeds...2019/12/02 · laba/ics or laba/lama/ics, chronic bronchitis, and...

An initiative of

OVERVIEW OF DRUGS

FOR ASTHMA/COPD

Asthma Medications

• Reliever Medications

• Controller Medications

• Add-On Controller Medications

Asthma Medications


• Short-Acting Beta2-Agonist bronchodilators (SABA)

• Low-dose ICS-formoterol

• Short-Acting Muscarinic Antagonists (SAMA)



Short-Acting Beta2-Agonists (SABA)

• Racemic Albuterol (S and R), Levalbuterol (R-albuterol)

• MOA: Beta2 receptor activation -> cAMP production ->

relaxation of airway smooth muscles

• Adverse effects

• Tremor

• Tachycardia

Short-Acting Beta2-Agonists (SABA)

• Inhaled SABAs provide quick relief of asthma

symptoms and bronchoconstriction including in

acute exacerbations

• Pre-treatment of exercise-induced

bronchoconstriction

• Use only as-needed and at the lowest

dose/frequency required

• Tolerance develops rapidly with regular use due

to reduced number of beta-2 receptors in lung

Asthma Medications




• Short-Acting Antimuscarinics (SAMA)



Low-dose ICS-formoterol

• ICS MOA: anti-inflammatory – block late-phase reaction

to allergens, reduce airway hyperresponsiveness, inhibit

inflammatory mediators

• LABA MOA: bronchodilator that increases cAMP->

decreases intracellular calcium -> produces smooth

muscle relaxation


• Low dose Beclometasone-formoterol or

Budesonide-formoterol

• Reliever for patients prescribed as-needed

controller therapy for mild asthma

• Substantially reduces the risk of severe

exacerbations compared with SABA-only

treatment


• Low dose Beclometasone-formoterol or

Budesonide-formoterol

• Reliever for patients with moderate-severe

asthma prescribed maintenance and reliever

treatment

• Reduces risk of exacerbations compared with

using as-needed SABA treatment, with similar

symptom control

Asthma Medications




• Short-Acting Muscarinic Antagonist (SAMA)



Short Acting Muscarinic Antagonist

(SAMA)


(SAMA)• MOA: inhibits bronchoconstriction by blockage of

muscarinic cholinergic receptors

• Adverse effects:

Dryness of mouth, bitter taste

• DOC for:

• Beta2 agonist intolerance

• Beta-blocker induced bronchospasm


(SAMA)• Long-term use:

less effective reliever than SABAs

• Short-term use in acute asthma:

added to SABA reduces risk of hospital admission

Asthma Medications



• Inhaled Corticosteroids (ICS)

• ICS and Long-acting beta2-agonist bronchodilatory combinations

(ICS-LABA)

• Leukotriene modifiers


Inhaled Corticosteroids

• Most effective anti-inflammatory medication

• Reduce symptoms

• Increase lung function

• Improve qualify of life

• Reduce risk of exacerbations and asthma-related

hospitalizations and death


• Low dose ICS provides most of the clinical benefit for

most patients

• Some patients may need medium dose ICS if asthma

uncontrolled despite good adherence/technique with low

dose ICS

• High dose ICS needed by very few patients

• Long-term use: increased risk of local/systemic side effects



• Inhaled, Local: oropharyngeal candidiasis, dysphonia

• Use spacer device; rinse and spit after use

• Oral, Systemic: osteoporosis, cataract, glaucoma,

adrenal suppression, dermal thinning

• Less common vs oral steroids

• Risk increased with long-term high dose ICS

ICS Bioavailability

• ~10-50% of MDI dose delivered to the lungs

• Nearly all of the amount delivered to the lungs is bioavailable.

• ~50-80% of MDI dose without a spacer is swallowed

• High first-pass metabolism or use of space can ↓oral bioavailability

Estimated Comparative Daily Dosages

for Inhaled Corticosteroids

Asthma Medications




• ICS and Long-acting beta2-agonist bronchodilatory

combinations (ICS-LABA)



ICS-LABA

• LABA Adverse effect: tachycardia, headache, cramps

• ICS-LABA is safe for asthma when used in combination

• LABA monotherapy should not be used in asthma:

increased risk of asthma-related death

ICS-LABA

• Addition of LABA to ICS

• Improves symptoms, lung function, and reduces

exacerbations in more patients, more rapidly, than

doubling the dose of ICS

• Maintenance and reliever treatment with low dose ICS-

formoterol reduces exacerbations compared with

maintenance therapy with SABA as reliever

Asthma Medications




• ICS and Long-acting beta2-agonist bronchodilatory combinations

(ICS-LABA)



Leukotriene Modifiers

• Montelukast, Pranlukast, Zafirlukast, Zilueton (tablets)

• MOA: inhibits leukotriene activity -> anti-inflammatory

effects

• Leukotrienes 100-1000x more potent bronchoconstrictor than

histamine

• Attracts inflammatory cells -> more mucus production

• Adverse effects: Few side effects except elevated liver

function test with zileuton and zafirlukast

Leukotriene Modifiers

• Used as an option for controller therapy, particularly in

children

• Used alone: less effective than low dose ICS

• Added to ICS: less effective than ICS-LABA

Asthma Medications




• Long-acting Muscarinic Antagonist

• Anti-IgE

• Antil-IL5 and anti-IL5R

• Anti-IL4R

• Systemic corticosteroids

Long-Acting Muscarinic Antagonist

(LAMA)

Tiotropium bromide 1.25mcg (soft mist inhaler)

2 puffs once daily

• Adverse effects: dry mouth

• Add-on option at Step 4 or 5 for patients with history of

exacerbations despite ICS ± LABA

Asthma Medications




• Long-acting anticholinergic

• Anti-IgE


• Anti-IL4R


Anti-IgE

• Omalizumab (subcutaneous)

• Add-on option for patients with severe allergic asthma uncontrolled

on high dose ICS

• Serum IgE: 30-700IU/ml

• MOA: inhibits the binding of IgE to the surface of mast

cells and basophils -> limits release of mediators of the

allergic response (histamines, leukotrienes, etc)

• Adverse effect: injection site reactions are common but

minor. Anaphylaxis is rare.

Antil-IL5 and Anti-IL5R

• Anti-IL5:

• Mepolizumab (subcutaneous)

• Reslizumab (IV)

• Anti-IL5 Receptor

• Benralizumab (subcutaneous)

• Add-on options for patients

with severe eosinophilic asthma

uncontrolled on high dose

ICS-LABA

• Adverse effect: injection site reactions are common but minor.

Anti-IL4R

• Dupilumab (subcutaneous)

• Add-on option for patients with severe eosinophilic or Type 2

asthma uncontrolled on high dose ICS-LABA, or requiring

maintenance OCS

• Adverse effect: injection site reactions are common but

minor.

Asthma Medications




• Long-acting anticholinergic

• Anti-IgE


• Anti-IL4R


Systemic Corticosteroids

• Prednisone, Prednisolone, Methylprednisolone,

Hydrocortisone

• Oral corticosteroid (OCS) therapy preferred

• Short-term treatment (5-7days): for severe acute

exacerbations, with main effects seen after 4-6 hours

• Long-term: may be required for patients with severe

asthma

Systemic Corticosteroids


• Short-term: hyperglycemia, fluid retention sleep

disturbance, reflux, appetite increase, mood changes

• Long-term: cataract, glaucoma, hypertension, diabetes,

adrenal suppression, osteoporosis, dermal thinning

COPD Medications

• Bronchodilators

• Beta2-Agonists

• Antimuscarinics

• Methylxanthines

• Combination bronchodilator therapy

• Anti-inflammatory Agents

• Inhaled Corticosteroids

• Phosphodiesterase-4 (PDE4) Inhibitors

• Oral Glucocorticoids

• Antibiotics

Bronchodilators

• Central to symptom management and commonly given on

a regular basis to prevent/reduce symptoms

• Inhaled bronchodilators recommended over oral

bronchodilators

• Regular and as-needed use of SABAs or SAMAs improve

FEV1 and symptoms.

• Combinations of SABA/SAMA are superior compared to

either alone in improving FEV1 and symptoms.

COPD Medications

• Bronchodilators

• Beta2-Agonists

• Antimuscarinics

• Methylxanthines






• Antibiotics

Short-Acting Beta2 Agonists (SABA)

• MOA: stimulates beta2-adrenergic receptors->↑ cyclic

AMP and produces functional antagonism to

bronchoconstriction -> relax airway smooth muscle

• Adverse effects: resting sinus tachycardia, potential to

precipitate cardiac rhythm disturbances in susceptible

patients

Long-Acting Beta2 Agonists (LABA)

Antimuscarinic Agents

• MOA: blocks the bronchoconstrictor effects of

acetylcholine on M3 muscarinic receptors expressed in

airway smooth muscle

• Adverse effects: dry mouth. *Inhaled antimuscarinics are

poorly absorbed which limits systemic effects


(SAMA)• Additional MOA: block the inhibitory neuronal receptor

M2, which potentially can cause vagally induced

bronchoconstriction

Long-Acting Muscarinic Antagonist

(LAMA)• Additional MOA: prolonged binding to M3 muscarinic

receptors, with faster dissociation from M2 muscarinic

receptors -> prolonged duration of bronchodilator effect

• Clinical trials have shown a greater effect on exacerbation

rates for LAMA treatment (tiotropium) versus LABA

treatment.

Methylxanthines

• MOA:

• PDE Inhibition: smooth muscle relaxation (ie, bronchodilation)

• Suppression of the response of the airways to stimuli

• Enhanced calcium uptake in muscle cells: increases diaphragmatic

muscles contractility


• Normal (10-15mcg/ml): N/V, tremor, tachycardia, HA, insomnia

• >20mcg/ml: arrhythmias, seizures

Methylxanthines

• Patients can be adequately treated with serum levels in

the 8-12 mcg/mL

• Theophylline addition to salmeterol produces greater

FEV1 improvement than salmeterol alone

• Evidence for modest bronchodilator effect compared to

placebo in stable COPD

• Data do not support a role for low-dose theophylline in

reducing the frequency of COPD exacerbations

• Theophylline not recommended unless other long

acting bronchodilators are unavailable or

unaffordable

Combination LABA/LAMA

• LABA/LAMA combination treatment increases FEV1 and

reduces symptoms and exacerbations compared to

monotherapy

COPD Medications

• Bronchodilators

• Beta2-Agonists

• Antimuscarinics

• Methylxanthines






• Antibiotics


• ICS alone does not modify long-term decline nor mortality

in COPD patients

• Chronic use of ICS increases the risk of pneumonia in

patients with severe COPD

Combination LABA/ICS

• Consider when exacerbations continue despite

appropriate long-acting bronchodilator therapy.

• Patients with blood eosinophil counts ≥ 100 cells/mcL

shown to have benefit with the addition of an ICS.

• May be used first-line in patients with blood eosinophil

counts ≥ 300 cells/mcL, or in patients who also have

asthma. Can combine with LAMA.

Triple Inhaled Therapy

• Adding a LAMA to existing LABA/ICS improves lung

function and patient reported outcomes – exacerbation

risk.

PDE4 Inhibitors

Roflumilast 250-500mcg PO daily

• MOA: PDE4 inhibitors prevents breakdown of cAMP ->

decreases inflammation and may promote airway smooth

muscle relaxation

• Consider use in patients with exacerbations despite

LABA/ICS or LABA/LAMA/ICS, chronic bronchitis, and

severe to very severe COPD (FEV1<50%)

• Beneficial effects report to be greater in patients with prior

history of hospitalization due to exacerbation

Oral Glucocorticoids

• MOA: inhibits multiple inflammatory cytokines, reduces

airway inflammation

• Benefit in COPD is less pronounced than in asthma

• Utilized in acute management of exacerbations

• Chronic daily treatment not recommended – lack of

benefit vs systemic complications

Antibiotics

• Macrolides for 1 year in patients prone to exacerbations

reduced exacerbation risk compared to usual care

• Azithromycin 250mg/day or 500mg 3x/week

• Erythromycin 500mg bid

• Preferentially for former smokers

• Azithromycin: increased incidence of bacterial resistance

and hearing test impairments

Drugs used in Both Asthma/COPD

• Bronchodilators

• Beta2-Agonists

• Long-Acting Anticholinergic: Tiotropium


• Combination ICS/LABA

• Oral Corticosteroids

An initiative of

an initiative of - calrightmeds...2019/12/02 · laba/ics or laba/lama/ics, chronic bronchitis, and...

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