Miscellaneous for Asthma

1- Abstract

2- Introduction

3- Examples of medications

4- Mechanism of action

5- Dose

6- Side effects

7- Benefits

8- Drug – Drug interaction

9- Drug – food interaction

10- Monographs

1- Abstract 

• Asthma is a complex and heterogeneous lung disease characterized by variable clinical presentations (phenotypes) and underlying mechanisms (endotypes). The primary pathological process in asthma is often driven by T helper type 2 (Th2) inflammation, mediated by cytokines such as IL-5, IL-4, and IL-13. This type of inflammation is responsible for about 50% of mild-to-moderate asthma cases and a significant portion of severe asthma cases.

2- Introduction

• Asthma is a chronic inflammatory disorder of the airways associated with bronchial hyper-responsiveness (BHR), reversible airflow limitation and recurrent symptoms of wheezing, chest tightness and cough. Etiologies includes genetic and environmental factors that together create a state of persistent inflammation of the lower respiratory tract that can be worsened by various trigger factors like allergen exposure, smoking, drugs and exercise. Cross-sectional surveys estimate that the prevalence of asthma has increased by about 38% in the past two decades. Explanations for this increased prevalence include a parallel rise in the prevalence of obesity and allergic rhinitis, as well as the levels of air pollution.

3- Examples of medications

• Examples of miscellaneous medications for asthma include several drug :

 1. Leukotriene Modifiers: Medications like montelukast (Singulair) and zafirlukast (Accolate) block leukotrienes, which are chemicals in the immune system that contribute to inflammation and asthma symptoms 

 2. Theophylline: This bronchodilator is taken daily in pill form and helps relax the airways. It is used for mild asthma and particularly for managing nighttime symptoms. Regular blood tests are often needed to ensure proper dosing due to potential side effects 

 3. Mast Cell Stabilizers: Cromolyn sodium (Intal) is an example that helps prevent the release of inflammatory substances from mast cells, reducing airway inflammation and bronchoconstriction).

 4. Anticholinergics: Ipratropium (Atrovent) and tiotropium (Spiriva) are used to prevent muscle tightening around the airways. These are typically added to other treatments for better control of asthma symptoms.

 5. Biologics: These are advanced treatments for severe asthma that target specific pathways in the immune system. Examples include omalizumab (Xolair), mepolizumab (Nucala), benralizumab (Fasenra), and reslizumab (Cinqair).

4- Mechanism of action

• -Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. 

• These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. 

• The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. 

• The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not posess any bronchodilator, antihistamine, or corticosteroid activity. 

5- Dose

1. Mild Intermittent Asthma 

   - Medication: Low-dose inhaled corticosteroids (ICS) as needed with a short-acting beta-agonist (SABA) for quick relief.

2. Mild Persistent Asthma 

   - Medication: Daily low-dose ICS plus a SABA as needed, or a combination low-dose ICS/formoterol used both as maintenance and relief therapy.

3. Moderate Persistent Asthma 

   - Medication: Low-dose ICS/long-acting beta-agonist (LABA) with SABA as needed, or low-dose ICS/formoterol as both maintenance and relief.

4. Severe Persistent Asthma 

   - Medication: Medium- or high-dose ICS/LABA combinations, potentially adding other treatments like tiotropium or biological agents (e.g., anti-IgE, anti-IL5) for patients who do not respond to standard therapies.

5. Specialized Treatments:

   - In cases of difficult-to-treat or severe asthma, additional therapies such as oral corticosteroids, biologics, and referral to a specialist for personalized treatment plans might be required.

6-Side effect 

• Inhaled Corticosteroids: These can cause oral thrush (a fungal infection in the mouth), hoarseness, and throat irritation. Using a spacer and rinsing the mouth after use can help mitigate these effects.

•  Short-acting Beta Agonists (e.g., Albuterol): Common side effects include jitteriness, increased heart rate, and shakiness. These symptoms are generally temporary and should pass within a few hours.

•  Long-acting Beta Agonists (LABAs): When used alone, these have been linked to severe asthma attacks. Therefore, they are typically prescribed in combination with inhaled corticosteroids. Side effects can include muscle cramps and heart palpitations.

• Leukotriene Modifiers (e.g., Montelukast): These can sometimes cause psychological side effects such as agitation, aggression, depression, and suicidal thoughts. It’s important to monitor for these reactions and consult a doctor if they occur.

• Theophylline: This bronchodilator can cause side effects like insomnia and gastroesophageal reflux. Regular blood tests are often required to ensure the correct dosage.

7- Benefits 

• Asthma medications provide several significant benefits, helping to manage symptoms and improve overall quality of life for individuals with asthma. These benefits vary depending on the type of medication used:

1. Inhaled Corticosteroids: These are the most effective long-term control medications for asthma. They reduce inflammation and swelling in the airways, leading to fewer asthma symptoms and attacks.

2. Long-acting Beta Agonists : These medications help to open the airways and reduce inflammation, providing long-term control of asthma symptoms, especially nighttime symptoms.

3. Leukotriene Modifiers: These oral medications block the action of leukotrienes, substances in the immune system that contribute to asthma symptoms. They help in preventing asthma attacks.

4. Quick-relief (Rescue) Medications: These include short-acting beta agonists like albuterol, which provide rapid relief from acute asthma symptoms. They are essential during an asthma attack as they quickly relax the muscles around the airways, making breathing easier.

8- Drug – Drug interaction

• The risk or severity of adverse effects can be increased when Omalizumab is combined with these drugs:

1. Aducanumab

2. Alemtuzumab

3. Alirocumab

4. Adalimumab

5. Abciximab 

• Theophylline can interact with a wide range of medications, leading to either increased or decreased levels of theophylline in the blood.

Some examples of drug interactions with theophylline include:

1. Increased Theophylline Levels:

- Ciprofloxacin

- Erythromycin

- Fluvoxamine

- Cimetidine

- Propranolol

2. Decreased Theophylline Levels:

    - Carbamazepine

    - Phenytoin

    - Rifampin

    - Smoking

    - Barbiturates

9- Drug – food interaction 

• Theophylline can interact with certain food sand beverages , potentially affecting its absorption or metabolism.

Some examples of drug-food interactions with theophylline include:

1. Caffeine:

Caffeine-containing beverages like coffee ,tea, and some soft drinks can increase the level of theophylline in the blood ,potentially leading to toxicity.

2. Grape fruit Juice:

Grape fruit juice can inhibit the metabolism of theophylline ,leading to increased blood level sand potential toxicity .It's best to avoid consuming grape fruit juice while taking theophylline.

3. High-FatMeals:

Consuming high-fat meals shortly before or after

taking theophylline may delay its absorption and

reduce its effectiveness .It's advisable to take theophylline.