Asthma & COPD Flashcards
What are the therapeutic targets?
- smooth muscle dysfunction
- airway inflammation
2 broad categories for the treatment of asthma
- bronchodilators
- anti-inflammatory agents
Bronchodilators
used to relieve acute symptoms and for control therapy; asthma attacks
Anti-inflammatory Agents
used to control or prevent symptoms
B2AR Agonists
2 kinds
SABAs: short-acting B2-selective agonists
LABAs: long-acting B2-selective agonists
Mainly treats SMOOTH MUSCLE DYSFUNCTION
Bronchodilators
3 types
- epinephrine
- ephedrine
- isoproterenol
Epinephrine
- bronchodilator
- non-selective adrenergic agonist
Ephedrine
- bronchodilator
- non-selective adrenergic agonist
- releases NE
Isoproterenol
- bronchodilator
- non-selective beta agonist
- not used as much anymore
SABAs
Short-Acting B2-Selective Agonists
- little rationale for choice among SABAs
- maximal bronchodilation is achieved in 15-30 minutes; persists 3-4 hours
- used for relief of acute asthma symptoms and brochospasms
FAST
LABAs
Long-Acting B2-Selective Agonists
- potent selective B2-agonists that are delivered by metered-dose or dry powder inhalers
- duration of action is >_ 12 hours, due to high lipid solubility
- NOT RECOMMEND AS MONOTHERAPY
- – lack any anti-inflammatory actions
- –WORK WELL WITH inhaled corticosteroids to improve asthma control
SLOW
Catch with LABAs
CAN NEVER BE GIVEN BY ITSELF
- continued use causes airways to be refractory/non-responsive
- NEED to pair with INHALED CORTICOSTEROIDS
Methylxanthines
(PDE inhibitors)
Mechanism
- catalyze breakdown of PDE and blunt response
- relax smooth muscle b/c keep cAMP around by preventing breakdown
Methylxanthines
PDE inhibitors
- relax bronchial smooth muscle
- anti-inflammatory properties
- reduce release of inflammatory mediators and cytokines
Theophylline
in treatment of asthma
- Methylxanthines
- effective for treatment of asthma
- – must be CAREFULLY regulated
- not widely used because of narrow TI; used when asthma is unresponsive to other drugs
Theophylline TI
Narrow TI
Which drug has a narrow TI
Theophylline
mathylxanthine
Muscarinic Receptor Antagonists
(SAMRA, LAMRA)
Mechanism
- block M2R/M3R receptors
- inhibits contraction from occurring
(rather than inducing dilation)
Anti-muscarinics
- not used much anymore
- – B2-selective agonists preferred
- has role in parasympathetic pathways
- many times COMBINED with B2-agonist to enhance dilatory effects
Smooth Muscle Dysfunction
- leads to (4 things)
leads to:
- bronchoconstriction
- bronchial hyperreactivity
- hyperplasia/hypertrophy
- inflammatory mediator release
Airway Inflammation
leads to:
- inflammatory cell infiltration/activation
- mucosal edema
- cellular proliferation
- epithelial damage
- basement membrane thickening
Anti-inflammatory agents
3 Types
- leukotriene modifiers
- corticosteroids
- biologics
Leukotrienes in Asthma
potent bronchoconstrictors and are associated with
- mucus hypersecretion
- increased bronchial reactivity
- mucosal edema
Leukotriene Modifiers
Strategy for Therapeutic Use
- inhibit 5-lipoxygenase (first step)
- – Zileuton
- block binding of LTD4 to CysLT receptor (inhibits further down the pathway
- – Zafirlukast
- – Montelukast
Leukotriene Modifiers
Considerations for Use
ALL ORAL
- all have different mechanisms
Zileuton
- dosage
- inhibits
Leukotriene Modifiers
- dosed 2 or 4x/day
- inhibits multiple CYPs
Zafirlukast
Leukotriene Modifiers
- dosed 2x/day
- inhibits multiple CYPs
Montelukast
Leukotriene Modifiers
- dosed 1x/day
- no hepatic toxicity and does NOT inhibit CYPS
- most widely used
Corticosteroids Therapeutic use in Asthma - target - effects - how administered
target: glucocorticoid receptors
- inhibit eosinophilic influx
- inhibit airway mucosal inflammation
- reduce frequency of exacerbations if administered chronically
- potentiate effects of B2 agonists (make effective for longer)
- oral steroids for urgent, short-term treatment (can be given high dose oral if emergent)
Corticosteroid Considerations
- ** Aerosol Rx most effective at minimizing systemic adverse effects ***
- lots of side effects when used long term
- use as little as possible to get desired results
Inhaled Corticosteroids
- bioavailability
- name 2
- extremely low bioavailability due to extensive first-pass hepatic metabolism
- – budesonide
- – fluticasone
Dual Controller Therapy in Asthma
ICS + LABA vs. increased-dose ICS
- much safer than LABA alone (DO NOT DO)
- helps mitigate patient being refractory to LABA or SABA
- escalating doses of ICS detrimental
ICS + LABA vs ICS + LTRA
*** patient dependent
Asthma control in patients using ICS + LABA
- dependent on severity
- used for exacerbation treatment
As disease gets more severe
add on additional therapies
- monoclonal antibodies only for those with severe asthma who is not responding to anything else
Biologics
Used For
used for:
- eosinophilic asthma
- allergic eosinophilic inflammation
- nonallergic eosinophilic inflammation
Omalizumab: Anti-IgE therapy
- mast cells BIG for allergic asthma: inhibit IgE & cut asthma off at the source (stops mast cell production)
- – lowers plasma IgE to undetectable levels
- injection
- lowers amount of corticosteroids needed
* indicated for use in patients with a positive skin test or in vitro reactivity to perennial aeroallergen*
Omalizumab Indication
Anti-IgE therapy
* indicated for use in patients with a positive skin test or in vitro reactivity to perennial aeroallergen*
Anti-IL5 or IL-5 Receptor therapy
- eosinophilic asthma
- affects maturation and differentiation of eosinophils; can also effect basophils
- injection
- ** Indicated for use in patients with eosinophilic asthma
Mepolizumab
Anti-IL5 or IL-5 Receptor therapy
Reslizumab
Anti-IL5 or IL-5 Receptor therapy
Benralizumab
Anti-IL5 or IL-5 Receptor therapy
Anti-IL5 or IL-5 Receptor therapy Indication
*** Indicated for use in patients with eosinophilic asthma
Anti-IL5 or IL-5 Receptor therapy
Benralizumab
Reslizumab
Mepolizumab
Mepolizumab & Reslizumab target CIRCULATING IL5
Benralizumab targets receptor level IL5
Clinical Pharmacology of Mild to Moderate Asthma
- bronchodilators are rapidly effective, safe, and inexpensive
- inhaled SABA on “as needed” basis
Additional treatment is necessary if:
- “rescue” therapy is required >2x/week
- nocturnal symptoms occur >2x/month
- FEV is <80% predicted
Clinical Pharmacology of Refractory and Severe Asthma
- ICS + LABA
- – marketed 2 in one inhalers
- if asthma is inadequately controlled– candidates for biologics
COPD
Irreversible
- common preventable and treatable disease
- progressive with enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases
- mainly effects older people
- symptoms worsen over time, with limited relief because so much destruction of lung
Drugs used in COPD
Bronchodilators
- anti-cholinergics
- B2 agonists
Clinical Pharmacology of COPD
inhaled bronchodilator and brochodilator-steroid combinations
Tiotropium Bromide (Spiriva)
COPD
- long-acting muscarinic receptor antagonists (LAMRAs)
Aclidinium Bromide (Tudorza)
COPD
- long-acting muscarinic receptor antagonists (LAMRAs)
Fluticasone-Vilanterol (Breo)
COPD
- corticosteroid-LABA combination
Budesonide-Formoterol (Symbicort)
COPD
- corticosteroid-LABA combination
Also used for asthma treatment
Revefenacin (Yupelri)
COPD
- LAMRA that specifically TARGETS M3 MUSCARINIC RECEPTORS OVER M2
Clinical Pharmacology of Acute COPD Symptoms
- inhalation of SABA, a SAMRA, or SABA-SAMRA combination
Clinical Pharmacology of Chronic COPD Symptoms
- LAMRA or a Corticosteroid-LABA combination is indicated
B2 Agonists
- naming
- Albuterol, Salmeterol, Formoterol
OL
Anti-muscarinics
- naming
- Tiotropium Bromide, Aclidinium Bromide
IUM Bromide
Leukotriene Receptor Antagonists
- Zafirlukast, Montelukast
KAST
Corticosteroids
- Fluticasone, Beclomethasone, Budesonide
SONE
Biologics
- Omalizumab, Mepolizumab, Benralizumab
MAB
budesonide
Inhaled corticosteroids
fluticasone
Inhaled corticosteroids
