Effectiveness of LABA-LAMA in COPD Treatment

Introduction:

The function of the lung is gaseous exchange. Carbon dioxide produced by the cellular metabolic processes is expelled out of the body, and oxygen, necessary for cellular activity, is inhaled. The elasticity of the lung tissue and morphology of the alveoli help in this process. Diseases in which the elasticity of the lung is lost make the breathing process difficult. As the normal gaseous exchange is lost, the normal physiological function of the body is impaired. Chronic obstructive pulmonary disease is a type of obstructive disorder of the lungs that makes breathing difficult. Over the years, several medications have been used in such cases to make breathing easier for such patients.

What Is COPD?

Chronic obstructive pulmonary disorder (COPD) is among the most common noninfectious inflammatory lung disorders. The main risk factor for such disorder is smoking, secondary smoking, and exposure to noxious stimuli like toxic gases, metals, and chemicals. Around 10 percent of the world's population is suffering from this disorder. This is responsible for around 3 million deaths in the world. This is caused by the progressive limitation of the respiratory tract.

Pathophysiology of COPD:

1. This is an inflammatory condition that involves lung tissue, airway pathways, and vasculature of the lung.

2. This inflammation is associated with the generation of free radicals and free oxygens. As a result, the oxidative stress upon the tissues is increased gradually. This leads to protease-antiprotease imbalances in the lungs. Neutrophils and macrophages are responsible for releasing inflammatory mediators.

3. All these factors are associated with the destruction of the alveolar sac. In the early stage, the destruction of the alveolar sac and constant irritation is associated with increased production of mucus. That's why, in the early stage of chronic obstructive pulmonary disease, patients complain of cough with sputum. This stage is known as chronic bronchitis. This is also associated with reduced mucociliary clearance and increased permeability of the airspace epithelial barrier.

4. The next phase of chronic obstructive pulmonary disease is known as emphysema. In this stage, the alveolar sac's destruction leads to obstructive lung changes. As discussed, the inflammatory process is responsible for the destruction of elastin fibers of the respiratory cartilage. This is the reason behind the collapse of the respiratory epithelium.

5. The destruction of elastin fibers is also associated with the imbalance of the protease–antiprotease. In healthy conditions, proteases are associated with cellular repair and regeneration processes. As the balance is altered in chronic obstructive pulmonary disorder, the repair of the fibers and cells is impaired. This causes the activation of fibroblasts and fibrosis of the lungs.

The symptoms of chronic obstructive pulmonary disease are:

1. Significant respiratory distress and shortness of breath.

2. Wheezing during respiration.

3. Tightness in the chest.

4. Chronic cough with white or yellow-colored sputum.

What Are the Bronchodilators?

Bronchodilators are a group of drugs that are used for the treatment of COPD. The function of the bronchodilator is to expand the airway passage and relaxation of the smooth muscles of the respiratory tract. As a result, the respiratory difficulty related to COPD is eliminated. Different types of bronchodilators are used in OPD are:

1. Short-Acting Bronchodilators: These types of bronchodilators act quickly within 15 -20 minutes of inhalation, and such bronchodilators are effective for relatively less duration. On the basis of drug types, bronchodilators are of two types; short-acting beta-agonists (SABA. Levalbuterol) and short-acting muscarinic antagonists (SAMA; Albuterol and Ipratropium belong to this group). These drugs are taken through various devices like inhalers, nebulizers, and metered dose inhalers (MDI; a pressurized device to deliver drugs).

2. Long-Acting Bronchodilators: These types of medicines are used to control breathing disorders in COPD patients. However, these drugs don't provide relief quickly but reduce respiratory distress for a longer duration of time. These drugs are of two types: LABAs (long-acting beta-2 agonists) and LAMAs (long-acting muscarinic antagonists).

What Is LABA?

These are long-acting beta-2 agonists. These drugs act on beta-2 adrenergic muscle receptors of the respiratory smooth muscles and increase the intercellular messenger. This causes the relaxation of muscles. Salmeterol, Indacaterol, Olodaterol, and Formoterol belong to this group of drugs. The mechanism of action of such drugs are:

• These drugs cause relaxation of the smooth muscles of the airway tract and help in bronchodilation.

• Effective lung volume is increased.

• Smooth muscle relaxation causes an increase in the inspiratory capacity. This is associated with a reduction in dyspnea (difficulty in breathing).

• The episode of exacerbations (sudden onset of respiratory distress) is reduced by the action of these drugs.

On the basis of their daily uses, these drugs can be differentiated into two types. Once daily, long-acting beta-2 agonists are known as ultra-LABA. Indacaterol (IND), Olodaterol (OLO), and Vilanterol (VIL) belong to ultra-Laba group. These drugs are taken once daily and are much more efficient than traditional LABA. Fumarate (FF) or Propionate (FP) and Salmeterol (SAL) are traditional LABA that is administered twice daily.

What Is LABA-LAMA?

The respiratory distress of COPD patients is mainly caused by blockage and loss of elasticity of the alveoli. The attachment of the alveoli is lost in this process. The upper airway tract is less affected by COPD. That is why LABA, which causes bronchial smooth muscle relaxation, is not effective in COPD cases. Long-acting muscarinic antagonists act on the M3 muscarinic receptors in airway smooth muscles. They bind more effectively to M3 muscarinic receptors and for a prolonged duration of periods. These drugs regulate the calcium concentration in the bronchial smooth muscles and cause more effective relaxation of the bronchial muscles.

For these reasons fixed dose combination of LABA-LAMA is used nowadays. The combined effect of both drugs helps to reduce respiratory difficulties more effectively. The proposed drugs combinations are:

• Umeclidinium/Vilanterol

• Tiotropium/Olodaterol

• Glycopyronium/Indacaterol

• Glycopyrrolate/Formoterol

• Aclidinium/Formoterol.

The formulation and combination of LABA-LAMA drugs are unique. Such drugs cannot be administered with the help of normal inhalers. Special devices are developed for this purpose. Active devices are based on energy which is needed for the production of aerosols. In passive devices, aerosol production is dependent upon the inhalation of the air stream. In such conditions, pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), and soft mist inhalers (SMI) are used for drug delivery.

To increase the efficiency of these drug combinations, corticosteroids are used to help reduce pulmonary inflammation. This is known as triple-drug therapy.

Conclusion:

Chronic obstructive pulmonary disease is a serious respiratory problem. Smoking and pollution are closely related to such problems. Long-acting beta-2 agonists alone can not eliminate all respiratory problems. A fixed-dose combination of LABA-LAMA can be beneficial in such cases. But rigid dosing, difficult availability, and costly drug delivery devices are potential drawbacks to this system.