Asthma and COPD: SABAs vs. LABAs

Short-Acting Beta-Agonists (SABAs) vs. Long-Acting Beta-Agonists (LABAs)

• The mechanism of action (MOA), indications, and step-wise therapy for asthma and COPD are key aspects
• Pulmonary pharmacology focuses on drug actions in the lungs, airway effects, and therapies for airway obstruction like asthma and COPD

Asthma & COPD

• Asthma is a chronic inflammatory condition involving airway inflammation and smooth muscle contraction

• COPD is characterized by respiratory tract inflammation, air trapping, hyperinflation, and alveolar wall destruction

• The therapeutic approach for asthma includes bronchodilators, which relax airway smooth muscle, and anti-inflammatory drugs

• COPD treatment relies mainly on bronchodilators, with inflammation often resistant to corticosteroids

• Inhalation is the preferred route of drug delivery, directly targeting airways and reducing systemic side effects

• Oral administration requires higher doses compared to inhaled, with dosages typically 20:1

• Intravenous route is reserved for severely ill patients; biologics are given subcutaneously

• Bronchodilators include β2 adrenergic agonists, theophylline, and anticholinergic agents

• Therapeutic challenges in asthma involve chronic inflammation and structural changes, requiring corticosteroids that aren't always curative

• COPD involves progressive airflow obstruction and inflammation, often complicated by comorbidities

• Inhalers, such as pressurized metered-dose inhalers, dry powder inhalers, and nebulizers, are vital for effective drug delivery

• Spacers are helpful to ensure medication reaches the airways, rather than being deposited in the mouth tissues

• Considerations when choosing an appropriate drug delivery device is particle size and device suitability for different age groups

Beta-2 Adrenergic Agonists

• Inhaled β2-selective agonists are structural variants, modified to confer β-receptor selectively to norepinephrine and epinephrine
• Activation of β2 receptors leads to bronchial smooth muscle relaxation via the Gs-adenylyl cyclase-cAMP-protein kinase A pathway
• There is indirect inhibition of the release of bronchoconstrictor mediators from inflammatory cells, like histamine, reducing mucosal edema and ACh release
• Additional effects that agonists produce prevent mediator release, increase mucus secretion, and decrease neurotransmission in airway cholinergic nerves
• Mediation of prevention of microvascular leakage to resist bronchial mucosal edema development after exposure to mediators

SABA (Short-Acting Beta-2 Agonists)

• "Rescue" meds are short-acting beta-2 agonists & "control" meds are long-acting beta-2 agonists
• MOA: Inhaled Short Acting Beta-2 Agonists. Rapid-acting and effective bronchodilators are used as needed for symptom relief
• Mainstay of treatment of acute asthma (rescue therapy). SABAs should be used on demand for symptom control
• If SABAs are required frequently, therapy should be stepped up
• Commonly used SABAs are albuterol (ProAir, Ventolin, Proventil ®) and levalbuterol (Xopenex ®), R isomer of albuterol
• If patients experiences cardiac side effects from albuterol, levalbuterol has less cardiac activity -Metaproterenol (Alupent ®) is liquid taken by mouth or for use in nebulizers -Pirbuterol (Maxair ®) is inhaled
• SABAs include metered-dose inhalers (MDIs) and nebulizer inhalable formulations -SABAs have a rapid onset of action of 1-5 minutes as well as a half-life of 6 hours or less

LABA (Long-Acting Beta-2 Agonists)

• Long-acting β2 agonists (LABAs) provides prolonged bronchodilation that is commonly used with inhaled corticosteroids (ICS)
• Combination inhalers with LABAs and corticosteroids are convenient, improve following directions, and provide complementary synergistic actions
• LABAs with a duration of action of 12 hours or more can occur due to their high fat solubility -Fat solubility concentrates in the lipid bilayer of smooth muscle cell membranes
• For asthma, LABAs should always be used in combination with an anti-inflammatory to reduce uncontrolled tissue inflammation.

Single-Drug Combination Inhalers

• Formoterol (Perforomist), Salmeterol (Serevent Diskus), Arformoterol (Brovana)

• Combined with ICS: Symbicort ® (Budesonide + Formoterol) & Advair (Fluticasone + Salmeterol) Black Box Warning exists for asthma related death with LABA monotherapy with these considerations Long-acting beta-2 agonists such as formoterol or salmeterol may increase risk of asthma-related death

• LABAs should ONLY be used as additional therapy if patients remain inadequately controlled by low-to-medium dose inhaled corticosteroids

• Never prescribe a LABA alone for asthma; combine with inhaled corticosteroids and/or mostly as SABA rescue for asthma

• Okay to prescribe LAMAs only for COPD After one week of use, tolerance may develop with long term use. But it recovers after 3 days Pulse therapy is a potential option Formoterol combined with an ICS is the recommended rescue bronchodilator of choice for asthma This combination is more effective and safer than overuse short-acting β2 agonists LABAs combine with inhaled glucocorticoids from long-term control of moderate to severe symptoms

24-Hour LABAs

• Exists as Breco and Trelegy
• Formetrol has a “fast” onset compared to almeterol, perhaps due to intemmediate solubility
• These drugs suppress asthma symptoms for extended time periods
• In COPD, LABAs improvde symptoms while reducing both air trapping and exacerbations
• Long-term use may lead to desensitization of receptors
• β2 agonists may lead to muscle tremor, tachycardia, hypokalemia, and ventilation-perfusion mismatch

Adverse Affects of Beta-2 Agonists

• Muscle tremor, tachycardia, hypokalemia
• Restlessness and hypoxemia
• Metabolic effects

Tolerance

• Tolerance may develop to bronchoprotective effects but not usually to bronchodilator effects, especially in airway smooth muscle
• Continuous use of corticosteroids prevents the development of tolerance in airway smooth muscle

H1 Antihistamines

• Includes first and 2nd generation differences
• Differences in Side effects profile
• Includes histamine, bradykinin and their antagonists

H1 and H2 receptors are distributed widely in the periphery and in the CNS, and their activation by histamine can exert local or widespread effects H3 receptors are mainly expressed in the CNS, especially such as basal ganglia, hippocampus, and cortex H3 agonists promote sleep and wakefulness, H4 receptors are detected in GI tract, dermal fibroblasts, and other Histamine receptors includes four GPCRs, each with some clinical and therapeuric treatments for conditions

Histamine plays a mainrole in conditions allergic responses that play with some clinical treatment for modulations Histaminereceptor within modulation include function, learning and memory H1 and H2 cardiovascular function H1 Receptors causes histamine function Receptor antagonist First gerneratin in case of H1 has the side effect of sedation and antihistamine Second generation has fewer CNS side effects in certain populations

• First Generation includes; Doxepin, Diphenhydramine, Chlorpheniramine, and Cyproheptadine
• Second generation includes; Olopatadine, Acrivastine, Cetirizine, Loratadine, and have anti-inflammatory properties; allergies conjunctivitis

Smooth Muscle, they antagonist inhibit actions of H1 receptors Capillary Permeability, reduces histamine, causes edema wheels Mast cell-Stablilixing The first generation increases the risk of falls

Leukotriene receptor (LTRA)

• Inhibited 5 lypoxygenose, benefit management of asthma.

Antagonist receptor

• Inhaled 5 LTRA
• Inflammatory release in lipid 2 is increasing release and product formation
• Inhibit enzymes in response
• Prevents Bron,mucus,and histamine

Antinmuscrin agents

• SAMA/Lama in muscarinic

Short acting muscrin antagonists

• Available with SABA
• Ipratropium

Long acting

• Spirva: in copd
• Antimustrinic less affected than the other for asthma used Iprotropium, same indication used, contra in; Narrow glaucoma, prostatic, bladder Toitropium; once maintenance: approved long once maintenance

Pharmacodynamics

• Less affected: Beta agonists, effective reducing air Tiotropium: long, once in copd leading

LABAS

• Laba dual with benifitcial effects for lung function
• Most effective treatment for all functions

Phosphodisterate 4 inhibitors

• Chemistry: Methozandrine structure:similar to caffeine, and theramine Mechanism: inhibition of of primary.
• Andogonsin receptors

Arthrotex can limit steroid Large function: increase effective b2 and affordablility

• Additions can improve lung Theophylline should not work with other blood levels

The treatment

• Has high fever causing seizure and arrythmias Oral non selective; reduces exacerbations Low function, and reduced effects on symptoms on long

The inhibitors Mast cells Inhibitors for both Medications are all

Interleukins

• Reduce side and can hurt as reactions.

Biologic agents

• Xolair; ige
• Reduces symptoms that are Prophalactac- allergic Subutanciously

Anti tussives

• Opioid And no opioid