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PHARMACOLOGICAL PROPERTIES OF DRUGS USED IN BRONCHIAL ASTHMA
IN A MODERN INTERPRETATION
¹Davurova Laylo
²Khimmatova Maryam
³Dovurov Ulugʻbek
¹Assistant Professor, Department of Clinical Pharmacology, Samarkand State Medical
University
²^³Faculty of Pharmacy, Samarkand State Medical University, students of group 503
https://doi.org/10.5281/zenodo.14787190
Abstract.
During an exacerbation of bronchial asthma, patients independently take 2-4
inhalations of albuterol or another short-acting beta-agonist (no more than 3 times at 20-minute
intervals) and, if possible, measure peak expiratory flow rate (PEF). ). If treatment is effective
(reduction in symptoms, PEF > 80% of baseline), hospitalization is not required. If treatment is
ineffective, symptoms are severe, or PEF is persistently < 80%, follow the treatment program
recommended by your doctor or go to the emergency department.
Keywords:
Pathophysiology, Clinical manifestations, Diagnostics, Treatment.
INTRODUCTION
Inhaled bronchodilators (beta-2 agonists and anticholinergics) are the mainstay of
treatment for bronchial asthma in the intensive care unit. In adults and older children, albuterol
inhalation using a metered-dose inhaler (MDI) and spacer is as effective as nebulizer use. Aerosol
therapy is preferred in young children because of the difficulty in adjusting metered-dose inhalers
and spacers. It should be noted that, contrary to popular belief, there is no evidence to support the
use of continuous beta-2 agonist nebulization over intermittent use. Data suggest that the
bronchodilator effect is improved when the device is operated with a helium-oxygen mixture
(heliox) rather than oxygen. Given the lower density of helium, it helps deliver bronchodilators to
the distal airways. However, the technical aspects of using helium for nebulization (availability,
calibration of helium concentration, need to use special masks to avoid dilution with room air)
limit its widespread use.
Subcutaneous adrenaline solution 1 mg/ml (1:1000) or terbutaline are alternatives for use
in children. Terbutaline may be preferred because of its lower cardiovascular effects and longer
duration of action compared to epinephrine, but it is expensive and is no longer manufactured in
large quantities.
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Subcutaneous administration of beta-2-agonists in adults carries an increased risk of
adverse cardiovascular effects. However, clinically significant adverse effects are rare and
subcutaneous administration may be beneficial in patients who do not respond to maximal doses
of inhaled therapy or who are not receiving effective nebulizer therapy (e.g., patients with severe
cough, poor breathing, or uncooperative patients).
Nebulized ipratropium may be used concomitantly with nebulized albuterol, only in
patients who do not respond adequately to albuterol. Some data support the use of high-dose beta-
2 agonists and ipratropium concomitantly as first-line therapy.
RESEARCH METHODS AND APPROACHES
Systemic corticosteroids (prednisone, prednisolone, methylprednisolone) should always be
given except in cases of mild exacerbations. They are not needed in patients whose PEF has
returned to normal after 1 or 2 doses of a bronchodilator. Intravenous and oral administration are
probably equally effective. Methylprednisolone can be given intravenously if an intravenous line
is already in place and can be switched to oral administration as needed or convenient. In general,
higher doses (50–60 mg prednisone once daily) are recommended for the treatment of more severe
exacerbations requiring inpatient treatment, while lower doses (40 mg once daily) are intended for
the outpatient treatment of milder exacerbations. Although there is insufficient information on the
optimal dose and duration of therapy, most clinical guidelines recommend 3–5 days in children
and 5–7 days in adults, and the severity and duration of exacerbations should be taken into account
( 1, 2 ).
Theophylline is not used in acute asthma attacks.
Magnesium sulfate relaxes smooth muscles, but its effectiveness in treating asthma
exacerbations in the emergency department is debated.
Antibiotics are indicated only if history, examination, or chest X-ray suggest an underlying
bacterial infection. Most infections that cause asthma exacerbations are likely to be viral in
etiology.
Supplemental oxygen is indicated for hypoxemia and should be given via nasal cannula or
face mask at a flow rate or concentration sufficient to maintain oxygen saturation >90%.
Reassurance and reassurance are the best approaches if the asthma exacerbation is caused
by anxiety. Anxiolytics and morphine are relatively contraindicated because they are associated
with respiratory depression and morphine can cause an anaphylactoid reaction due to histamine
release from mast cells; these drugs can increase mortality and the need for mechanical ventilation.
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If patients do not return to baseline within 4 hours of receiving intensive emergency care,
hospitalization is usually required. The criteria for hospitalization vary, but typical indications
include:
a.
No improvement.
b.
Development of fatigue
c.
Relapse after retreatment with beta-2-agonists
d.
Significant decrease in PaO2 (< 50 mmHg)
e.
Significant increase in PaCO2 (> 40 mmHg)
f.
A significant increase in CO2 pressure indicates progressive respiratory
failure.
RESEARCH RESULTS
To improve the work of breathing, patients who are deteriorating despite aggressive
treatment may require noninvasive positive pressure ventilation (NIPPV). In the event of
respiratory failure, endotracheal intubation and invasive mechanical ventilation may be required.
NVP can be used to avoid intubation at the beginning of a severe exacerbation and should be
considered in patients with acute respiratory distress syndrome with an unreasonably high PaCO2
relative to the tachypnea level. The procedure is indicated in patients with tachypnea (respiratory
rate > 25 breaths/min), accessory muscles of respiration involved, PaCO2 > 40 but < 60 mmHg
Art., and hypoxia. Mechanical ventilation should be used instead of NIPPV only in the following
cases:
Глава 1
PaCO2 > 60 mmHg Art.
Глава 2
Change of consciousness
Глава 3
Excessive secretion of the respiratory tract
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Глава 4
Facial cranial anomalies (e.g., surgical, traumatic) that may interfere
with noninvasive ventilation.
Глава 5
If there is no significant improvement after 1 hour of NVP, the issue
of artificial ventilation should be carefully considered.
In cases of intubation and mechanical ventilation, sedation may be used to reduce the work
of breathing, but the routine use of muscle relaxants should be avoided because interactions with
corticosteroids may result in prolonged neuromuscular weakness. Ketamine may be used to
intubate the patient while awake, provided the physician is aware of its use and side effects (e.g.,
laryngospasm, rigidity, and bronchospasm).
Volumetric cyclic ventilation is commonly used in the assist-control mode because it
provides continuous alveolar ventilation in the presence of high and variable airway resistance.
The device should be set to a relatively low respiratory rate and a relatively high flow rate (> 80
L/min), which allows for increased expiratory flow and minimizes automatic positive expiratory
pressure (auto-PEEP). The initial tidal volume can be set to 6–8 ml/kg of ideal div weight, and
external PEEP should be used to facilitate the patient's initiation of mechanical ventilation and to
minimize machine synchronization during automatic PEEP. High peak airway pressures are
common because they result from high airway resistance and high inspiratory flow rates. In such
patients, peak airway pressures do not reflect the degree of lung expansion due to alveolar pressure.
However, if the plateau pressure exceeds 30–35 cm H2O, st., then the tidal volume of the device
should be reduced to limit the risk of pneumothorax. When tidal volume reduction is necessary,
moderate hypercapnia ("permissive hypercapnia") is acceptable, but if the arterial pH falls below
7.10, slow administration of sodium bicarbonate to maintain the pH at 7.20 to 7.25 may be
considered, especially in the presence of hemodynamic instability. Patients can usually be weaned
from the ventilator quickly once the airway obstruction is relieved and arterial PaCO2 and pH
normalize. (For more information, see Respiratory Failure and Mechanical Ventilation.)
Other therapy
Other treatments for asthma exacerbations have been reported to be effective, but none
have been fully studied. A mixture of helium and oxygen (heliox) is used to improve ventilation
by reducing the work of breathing and reducing the turbulent flow caused by helium, a less dense
gas than oxygen. Despite the theoretical advantages of heliox, research results have yielded
conflicting results regarding its effectiveness; its use may also be limited by its unavailability and
inability to provide high concentrations of oxygen at the same time (since helium is 70–80% of
the inhaled gas). However, heliox may be useful for treating patients with vocal cord dysfunction
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In patients with asthma, general anesthesia with agents such as sevoflurane and isoflurane
induces bronchodilation by an unclear mechanism, either through a direct relaxant effect on airway
smooth muscle or by attenuation of cholinergic regulation of arousal.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to
Aspergillus species (usually A. fumigatus) that occurs primarily in patients with asthma and, less
commonly, cystic fibrosis. Immune reactions to Aspergillus antigens lead to airway obstruction
and, if untreated, to bronchiectasis and pulmonary fibrosis. The signs and symptoms are consistent
with those of bronchial asthma, with productive cough, sometimes fever, and anorexia. To confirm
the diagnosis, skin testing for Aspergillus is performed and levels of IgE, circulating precipitins,
and antibodies to A. fumigatus are determined. In refractory cases, treatment is with corticosteroids
and itraconazole.
Allergic bronchopulmonary aspergillosis develops when the airways of a patient with
asthma or cystic fibrosis are colonized by Aspergillus species (fungi found in soil).
Pathophysiology
For unknown reasons, colonization in these patients leads to the production of antibodies
(IgE and IgG) and cellular immune responses (type I, III, and IV hypersensitivity reactions) to
Aspergillus antigens, which leads to frequent, recurrent exacerbations of asthma. Over time, the
immune responses, combined with the direct toxic effects of the fungus, lead to airway damage
with dilation and, ultimately, the development of bronchiectasis and fibrosis. Histologically, the
disease is characterized by airway obstruction with mucus, eosinophilic pneumonia, infiltration of
alveolar septa with plasma and mononuclear cells, and an increase in the number of bronchiolar
mucous glands and cuboidal cells
Rarely, other fungi, such as Penicillium, Candida, Curvularia, Helminthosporium, and
Drechslera, cause a similar syndrome called allergic bronchopulmonary mycosis; in this case,
bronchial asthma or cystic fibrosis are not present.
Aspergillus is present in the lumen of the airways, but invasion does not occur. Thus, it
must be distinguished from ABPA
Invasive aspergillosis affecting immunocompromised patients
Aspergillomas, which are clusters of Aspergillus, have been identified in patients with lung
cavities or cysts.
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Aspergillus pneumonia is rare and occurs in patients who have been taking low doses of
prednisone for a long time (for example, in patients with chronic obstructive pulmonary disease).
Despite clear differences, similar syndromes were observed.
Clinical manifestations
Symptoms resemble those of an exacerbation of bronchial asthma or pulmonary cystic
fibrosis; in addition, there is a cough with dirty green or brown sputum, and sometimes hemoptysis.
Fever, headache, and anorexia are common systemic signs of severe illness. Symptoms are
manifestations of airway obstruction, characteristic of which are wheezing and prolonged
exhalation, which are also observed during exacerbations of bronchial asthma.
Diagnostics
a.
History of bronchial asthma
b.
Chest X-ray or high-resolution computed tomography scan
c.
Aspergillus antigen skin test
d.
Aspergillus Aspergillus precipitins in blood
e.
Positive sputum culture for Aspergillus species (or less commonly other fungi)
f.
IgE level
g.
Eosinophil content in the blood
In patients with asthma or cystic fibrosis, the presence of recurrent exacerbations of the
disease, the presence of migratory or fixed infiltrates on chest radiography (often due to atelectasis
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due to the presence of mucus plug and bronchial obstruction), bronchiectasis on imaging and a
positive culture result for A. fumigatus, or marked peripheral blood eosinophilia should be
suspected.
CONCLUSION
When the diagnosis is suspected, the most appropriate first step is a skin prick test with
Aspergillus antigen, but serological testing using the Aspergillus precipitation test may be a more
practical initial test. An immediate allergic reaction to the test with clear skin signs (papules,
redness, and rash) is a reason to measure serum IgE levels and antibodies to Aspergillus
(precipitins), since up to 25% of patients with asthma without allergic bronchopulmonary
aspergillosis have a positive skin test. An IgE level > 1000 ng/ml (> 417 IU/ml) and a positive
precipitation indicate the diagnosis, which should be confirmed by measuring Aspergillus-specific
immunoglobulins (up to 10% of healthy patients have circulating precipitins). If ABPA is
suspected, the diagnosis is confirmed by the concentration of A. fumigatus-specific IgG and IgE
antibodies, if it is at least twice as high as in patients without ABPA.
Sputum and bronchoscopic Aspergillus cultures have low sensitivity and specificity for the
diagnosis of ABPA and are not included as diagnostic criteria.
In cases where test results are conflicting, such as when serum IgE levels are elevated but
A. fumigatus-specific immunoglobulins are not detected, the test should be repeated and the patient
followed over time to confirm or rule out the diagnosis.
Patients with stage I disease should receive 0.5–0.75 mg/kg of prednisone once daily for
2–4 weeks, then taper over 4–6 months. Chest radiography, blood eosinophil counts, and IgE levels
should be performed quarterly to monitor progress toward improvement, defined as the detection
of infiltrates, a ≥50% reduction in eosinophil counts, and a ≥33% reduction in IgE levels. Patients
who have progressed to stage II disease require only annual monitoring.
Stage II patients who relapse (stage III) receive another course of prednisone. Stage I or III
patients who fail prednisone therapy (stage IV) are candidates for antifungal agents. Itraconazole
200 mg twice daily for 16 months is used as a replacement for prednisone. In addition, pooled data
identify biologics such as omalizumab as steroid-sparing agents. Treatment of symptoms and
complications in stage V patients is usually supportive.
Itraconazole therapy requires monitoring of blood drug concentrations, liver enzymes,
triglycerides, and potassium levels.
All patients should be treated for the underlying disease, such as bronchial asthma or cystic
fibrosis. In addition, patients on long-term corticosteroid therapy should be carefully monitored
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for complications such as cataracts, diabetes mellitus, and osteoporosis; such patients may be given
prophylactic treatment to prevent bone demineralization and Pneumocystis jirovecii pulmonary
infection.
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