Pharmacotherapy for Respiratory Disorders Essay Paper

Bronchoconstriction, inflammation, and loss of lung elasticity are the most common processes that result in respiratory compromise. Bronchoconstriction can be treated with adrenergic agonists, cholinergic antagonists, and some other compounds. Inflammation is treatable with corticosteroids. Obstruction of the airways can also occur with infection and increased secretions. The infection is treated with antibiotics. Because the antibiotics and steroids have been covered elsewhere, this chapter focuses on the bronchodilators. Most of this will be a review from autonomics.

Drugs used in the treatment of bronchoconstriction include inhaled corticosteroids, β-agonists, cholinergic antagonists, and methylxanthines.

If you add cromolyn and the leukotriene modifiers, which are prophylactic agents, and corticosteroids for chronic treatment, you are all set.

Most of these drugs are now administered by inhalation. This gets the drug to the site of action and limits the systemic effects.

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Interleukin-5 (IL-5) antibodies will also reduce inflammation by binding to IL-5 and blocking its binding to the IL-5 receptor on the surface of eosinophils. Since IL-5 is the major cytokine involved in growth, differentiation, and activation of eosinophils, it makes sense that inhibiting the action of IL-5 will reduce production of eosinophils and reduce airway inflammation. Two IL-5 antibodies are available at this time—reslizumab and mepolizumab (note ‘mab’ ending).Pharmacotherapy for Respiratory Disorders Essay Paper

Inhaled short-acting β2-agonists are the most effective drugs available for treatment of acute bronchospasm and for prevention of exercise-induced asthma. β2-Selective agents are preferred, to avoid the cardiac effect of β1-activation. Use of long-acting β2-agonists has been associated with an increased risk of asthma-related death, intubation or hospitalization, and it is no longer recommended that long-acting β2-agonists be used as monotherapy for asthma.

There are a number of β-agonists that are used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

In an emergency, such as the bronchoconstriction associated with anaphylaxis, epinephrine can be used. Use of a short-acting β-agonist more than two to three times a week means that the asthma is not well controlled and adjustments to baseline medication need to be made. Long-acting β-agonists can be used in combination with inhaled corticosteroids to control asthma symptoms.

The respiratory system extends from the nose and upper airway to the alveolar surface of the lungs, where gas exchange occurs. Inhaled tobacco smoke moves from the mouth through the upper airway, ultimately reaching the alveoli. As the smoke moves more deeply into the respiratory tract, more soluble gases are adsorbed and particles are deposited in the airways and alveoli. The substantial doses of carcinogens and toxins delivered to these sites place smokers at risk for malignant and nonmalignant diseases involving all components of the respiratory tract including the mouth.

Consider, for example, the lungs of a 60-year-old person with a 40-pack-year1 smoking history starting at age 20 years. By age 60 years, this person will have inhaled the smoke from approximately 290,000 cigarettes and will bear a substantial risk for chronic obstructive pulmonary disease (COPD) and lung cancer. The dose of inhaled toxic particles and gases received from each of these cigarettes varies depending on the nature of the tobacco, the volume and number of puffs of smoke drawn from the cigarette, the amount of air drawn in through ventilation holes as the smoke is inhaled, and local characteristics within the lung that determine the diffusion of toxic gases and the deposition of particles. Because of this repetitive and sustained injurious stimulus, the repair and remodel process that heals the damaged lung tissue takes place at the same time the lung’s defenses continue to deal with this unrelenting inhalation injury.Pharmacotherapy for Respiratory Disorders Essay Paper

This chapter addresses the mechanisms by which tobacco smoke causes diseases other than cancer in the lower respiratory tract: the trachea, bronchi, and lungs. Beginning with the first Surgeon General’s report in 1964 (U.S. Department of Health, Education, and Welfare [USDHEW] 1964), cigarette smoking has been causally linked to multiple diseases and to other adverse effects on the respiratory system (Table 7.1). In addition to causing lung cancer and COPD, smoking increases the risk of death from pneumonia and causes chronic bronchitis (U.S. Department of Health and Human Services [USDHHS] 2004). Typically, the lungs of smokers show evidence of diffuse changes affecting the lining of the airways, the epithelium, and the structure of the bronchioles, which are the smaller air-conducting tubes.

Causal conclusions on smoking and diseases of the respiratory tract other than lung cancer: the 2004 and 2006 reports of the Surgeon General.

Previous reports of the Surgeon General have also addressed the effects of smoking on the respiratory tract. In discussing the plausibility of associations of cigarette smoke with chronic bronchitis and emphysema, the 1964 report gave full consideration to the nature of tobacco smoke and its effects on the respiratory tract (USDHEW 1964). That report concluded that cigarette smoking “… is the most important of the causes of chronic bronchitis in the United States…” (p. 302) and that “a relationship exists between pulmonary emphysema and cigarette smoking, but it has not been established that the relationship is causal” (p. 302). The 1984 report, which focused on COPD, covered mechanisms by which smoking affects the lung’s structure and function and the deposition and toxicity of cigarette smoke in the lung (USDHHS 1984). The report concluded that “cigarette smoking is the major cause of chronic obstructive lung disease in the United States…” (p. vii). The mechanisms of lung injury were considered further in the 1990, 2004, and 2006 reports (USDHHS 1990, 2004, 2006).

Air pollution has become a major global threat to human health. Historically, multiple major episodes of air pollution occurred world wide in the early twentieth century have produced severe health outcomes. Most tragically, the “killer fog” in London in 1952 has caused 12,000 unexplained deaths and severe long-term effects in human health.1Even in 2012, indoor and outdoor air pollution still caused an estimated 6.5 million deaths, which covers 11.6% of total global deaths.2 Exposure to air pollutants mostly occurs in industrial and rural areas due to various manufacturing, traveling, and living activities. Multiple review articles and meta-analyses have described a direct impact of air pollutants on respiratory responses and diseases.3, 4, 5, 6, 7 We will focus on the liaison of the later onset of respiratory diseases in childhood and adulthood with early life exposure to air pollutants at prenatal and perinatal stages.Pharmacotherapy for Respiratory Disorders Essay Paper

Air pollutants

Air pollutants have complex chemical and physical features dependent on the sources of pollutants. Outdoor air pollutants are either derived from human activities, such as industrial emissions, road traffic, residential heating, shipping, air traffic, construction, agricultural activities, war and fire accidents, or from natural hazards, such as earthquake, tsunami, volcanic eruption, spontaneous forest fires, and extreme temperature.8, 9 Although natural hazards occur independent of human activities, they affect the living environment, health, and lives of humans as hazardous events.4, 10Indoor air pollutants are generally released from smoking, building materials, air conditioning, house cleaning or air refreshing proucts, heating, lighting, and wood, fuel, or coal usage in cooking.6 Chemically, these pollutants can be presented as the vapor forms of inorganic pollutants, such as ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2), or as the vapor forms of organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), monocyclic hydrocarbons benzene, toluene, xylene, and aliphatic chemicals.4, 5 The particulate forms of air pollutants, however, usually consist of an inner carbon core with various organic pollutants and/or heavy metals on the surface (Fig. 1). The most harmful forms of particulate matter (PM) include PM10 (<10 μm in aerodynamic diameter), fine particles PM2.5 (<2.5 μm), and ultrafine particles (less than 0.1 μm or 100 nm), which can be released from diesel engines, volcanoes, asbestos, unpaved roads, plowing, burning fields, lint, pollens, and spores.11, 12 Detailed chemical components of these air pollutants have been summarized in multiple reviews4, 5, 6, 13, 14, 15 and we will focus on the health impact of these air pollutants with different chemical and physical natures. The principal nonmalignant respiratory diseases caused by cigarette smoking—COPD, emphysema, chronic bronchitis, and asthma—are defined in Table 7.2. The definitions indicate that chronic bronchitis is a specific set of symptoms, whereas emphysema refers to a particular pattern of lung damage. COPD comprises a clinical syndrome characterized by limitation in airflow; persons with COPD often have chronic bronchitis as well, and their lungs typically display emphysema. Other nonmalignant respiratory diseases that have been linked to smoking include asthma and idiopathic pulmonary fibrosis (USDHHS 2004), but the evidence has not reached a level of certainty sufficient to warrant a conclusion of cause and effect.Pharmacotherapy for Respiratory Disorders Essay Paper The nonmalignant respiratory diseases caused by smoking contribute substantially to the burden of morbidity and mortality attributable to smoking in the United States (Table 7.1). In 2005, the Centers for Disease Control and Prevention (CDC) estimated that an average of 123,836 deaths per year could be attributed to lung cancer caused by smoking for the period 1997–2001 (CDC 2005). CDC estimated an additional 90,582 deaths from COPD and 10,872 from pneumonia and influenza annually. Great advances have been made in our understanding of how smoking causes these diseases. Research has been facilitated by methods that directly assess changes in the lungs. Methods for obtaining biologic material from human lungs include bronchoalveolar lavage (BAL), a technique that allows recovery of cellular and noncellular components of the epithelial surface of the lower respiratory tract (Cantrell et al. 1973; Hunninghake et al. 1979; Reynolds 1987). BAL is of value in the study of immune and inflammatory mechanisms in the lower airways, because most of the cells recovered are believed to be derived from both air spaces and lung interstitium. Lung tissue obtained by biopsy or autopsy procedures can be used for cellular, protein, and nucleic acid assays. Exhaled breath condensate provides information about the composition of epithelial lining fluid (ELF) that can be used to detect inflammation and redox disturbance (Paredi et al. 2002). Blood samples may be used to assess systemic inflammatory responses, and blood cells serve as a source of nucleic acids. Characteristics of Tobacco Smoke Tobacco smoke, which comprises an aerosol (a mixture of solid and liquid particles) and gases, has thousands of chemical components, including many well-characterized toxins and carcinogens (International Agency for Research on Cancer [IARC] 2004). Many of these components are in the gas phase, and others are components of the particles. Nicotine, for example, is bound to particles in mainstream smoke. The chemical components in tobacco smoke were covered comprehensively in IARC Monograph 83 (IARC 2004) and described in previous reports of the Surgeon General. Numerous components of the smoke have the potential to injure the airways and alveoli. Components of tobacco smoke with the potential to injure the lungs through a variety of mechanisms are listed in Table 7.3. Some components adversely affect host defenses; others act through specific or nonspecific mechanisms. Notably, cigarette smoking has very strong oxidant potential in that both the gas and tar phases contain high concentrations of free radicals (Repine et al. 1997). Many of the components of cigarette smoke are the targets of regulations because of their toxic effects: these include nitrogen dioxide, carbon monoxide, and various metals. For information on the toxic effects of components, see reports of the U.S. Environmental Protection Agency (EPA) and other agencies (USEPA 1993, 2000; USDHHS 2000) and standard resources in toxicology (Gardner et al. 2000; Klaassen 2001).Pharmacotherapy for Respiratory Disorders Essay Paper Selected components of cigarette smoke and potential mechanisms of injury. Assessment of toxic effects of cigarette smoke in the respiratory tract requires consideration of the complexity of the mixture inhaled and the possibility of synergistic interactions among its many components. Although it is little studied, the possibility of numerous interactions has great plausibility because of the myriad components of cigarette smoke and the interlocking pathways of lung injury. Dosimetry of Tobacco Smoke in the Respiratory System To protect the lungs from injury, the respiratory tract has an elegant set of mechanisms for handling the particles and gases in inhaled air (Figure 7.1). These defenses include physical barriers, reflexes and the cough response, the sorptive capacity of the epithelial lining, the mucociliary apparatus, alveolar macrophages, and immune responses of the lung (Schulz et al. 2000). These defenses are critical because of the substantial volume of air inhaled daily: about 10,000 liters per day are inhaled by an adult. Even harmful substances present at low concentrations may eventually achieve a toxic dose after sustained exposure. In addition, high-level exposures, particularly when sustained, may overwhelm the lung's defenses, and some agents have the potential to reduce the efficacy of these defenses. Cigarette smoke, for example, contains components that impair mucociliary clearance (Table 7.3). Lung defenses. Source: Cook 2000. Reprinted with permission from Elsevier Health, © 2000.Pharmacotherapy for Respiratory Disorders Essay Paper The size of particles in the smoke inhaled directly from a cigarette (mainstream smoke) has been studied in a variety of systems. These studies indicate that the mass median aerodynamic diameter of particles is 0.3 to 0.4 micrometers (μm) (Martonen 1992; Bernstein 2004). Particles of this size penetrate to and are deposited in the deep lung. The handling of particles by the lung's defense mechanisms depends on their size (Figure 7.2). Large particles (e.g., many pollens and road dust) are removed in the upper airway, largely by impaction (USDHHS 1984). Small particles, with a mean aerodynamic diameter less than about 2.5 μm, reach the lungs, where they deposit in airways and alveoli by impaction, sedimentation, or diffusion. About 60 percent of the particles inhaled in mainstream smoke are deposited. Although these particles are subject to handling by the mucociliary apparatus and alveolar macrophages, removal is not complete because of their very high numbers in the lungs of long-term smokers, which show evidence of a substantial burden of retained particles. Similarly, evidence shows that smokers clear these particles at a reduced rate (Cohen et al. 1979; USDHHS 1984; Kreyling and Scheuch 2000). Fractional deposition of inhaled particles in the human respiratory tract. Source: Oberdörster et al. 2005. Reprinted with permission from Environmental Health Perspectives, © 2005. Figure based on data from the International Commission (more...) The removal of gases in the respiratory tract is accomplished through sorption by the liquid that lines the epithelial layer (Kreyling and Scheuch 2000). Both the site and the efficacy of removal of gases depend on the solubility of the gas. Highly soluble gases are removed high in the respiratory tract, but insoluble gases (e.g., carbon monoxide) may reach the alveoli and diffuse across the alveolar-capillary membrane. These dosimetric considerations indicate a high potential for lung injury in active smokers, who inhale a rich mixture of gases and particles that penetrates throughout the lungs, with deposit of particles and sorption of gases in the two anatomic sites most critical to respiration, the airways and alveoli.Pharmacotherapy for Respiratory Disorders Essay Paper Major Pulmonary Diseases Caused by Smoking This section provides a brief overview of the principal diseases of the lung that are caused by smoking. A brief description of pathophysiology and pathogenesis is provided as background for the more comprehensive discussions of mechanisms. These topics are covered in great detail elsewhere (Mason et al. 2005) and were addressed in the 1984 and 2004 Surgeon General's reports (USDHHS 1984, 2004). Chronic Bronchitis The symptom complex of chronic bronchitis has been investigated for decades. In the 1950s, the British Medical Research Council suggested that a diagnosis of chronic bronchitis was warranted when the symptoms of chronic cough and production of sputum were present on most days of the month for at least three months in two consecutive years without any other explanation (BMJ1965). This proposal is reflected in the current definition of chronic bronchitis (Table 7.2). Earlier, Reid (1960) had used the size of the mucous gland layer as a predictor for the postmortem diagnosis of this condition but did not implicate the inflammatory process in the pathogenesis of either enlargement of the gland or the production of excess mucus. Subsequent studies of lung tissue surgically removed from cancer patients (Figure 7.3) have shown that the symptoms of chronic bronchitis are associated with an inflammatory response involving the mucosal surface, submucosal glands, and gland ducts, particularly in the small bronchi that are 2 to 4 millimeters (mm) in diameter (Mullen et al. 1985; Saetta et al. 1997). In addition, longitudinal studies of chronic bronchitis in persons with normal lung function have clarified that its presence does not predict future progression to more severe obstructive lung disease (Fletcher et al. 1976; Saetta et al. 1997). Presence of chronic bronchitis in persons who already have limited airflow, however, is predictive of a more rapid decline in lung function and a higher risk of hospitalization than are seen with a similar limitation of airflow but no chronic bronchitis (Saetta et al. 1997).Pharmacotherapy for Respiratory Disorders Essay Paper Comparison of normal bronchial gland (A) with enlarged bronchial glands (B and C) from a patient with chronic bronchitis. Source: Hogg 2004. Reprinted with permission from Elsevier, © 2004. Note: (A) Histology of bronchus with epithelial lining (more...) The inflammatory immune cells that infiltrate the epithelium, subepithelium, and glandular tissue in chronic bronchitis include the polymorphonuclear neutrophils (PMNs), macrophages, CD8-positive (CD8+) and CD4-positive (CD4+) T lymphocytes, and B cells that are part of the adaptive inflammatory immune process (Di Stefano et al. 1996; O'Shaughnessy et al. 1997; Saetta et al. 1997). This chronic inflammation, consisting of enlargement of the mucous glands and remodeling of the walls of both large and small bronchi reflects a deregulated healing process in tissue persistently damaged by the inhalation of tobacco smoke (Hogg 2004). The consequences of this process include both the development of a chronic cough and the accumulation of excess mucus in the airway's lumen. However, this inflammatory process has little influence on airflow limitation unless it extends to the small conducting airways that account for much of the increase in airway resistance in COPD. Studies reported from the laboratory of Snider and associates in Israel (Breuer et al. 1993) were the first to show that elastase from PMNs was an important agent for the secretion of mucus by epithelial goblet cells. Later, Nadel (2001) and other investigators (Takeyama et al. 1999, 2000, 2001a,b; Burgel et al. 2000; Lee et al. 2000; Kohri et al. 2002) extended these observations by linking the PMN-induced production of mucin to stimulation of EGFR. They showed that PMN elastase triggered the cleavage of membrane-tethered transforming growth factor alpha (TGFα), allowing it to attach to the external binding site of EGFR. This step is followed by phosphorylation of the intracellular component of this receptor and stimulation of downstream signaling pathways that activate the expression of the MUC5AC gene and lead to the production of mucus (Takeyama et al. 1999). This type of experiment established that EGFR and its ligands provide a regulatory axis for the production of mucin that involves several membrane-bound ligands of EGFR, such as TGFα and heparin-binding EGF. Nadel (2001) has also shown that reactive oxygen species (ROS) can bypass the extra-cellular sphere of influence of this regulatory axis. Other studies have shown that ROS can directly activate EGFR's intracellular domain (Burgel et al. 2000; Takeyama et al. 2000; Kohri et al. 2002).Pharmacotherapy for Respiratory Disorders Essay Paper In many Asian nations, particularly China, air pollution is increasingly being recognised as an important emerging environmental and public health issue. A previous work has shown that levels of ambient air pollution are associated with an elevated incidence of respiratory diseases and reported the prevalence of respiratory symptoms,1particularly asthma, pulmonary emphysema and chronic bronchitis.2Atmospheric pollution caused by particulate matter less than 2.5 μm in diameter (PM 2.5) is reported to be particularly acute in China and in surrounding countries as a result of wind dispersal. This is a growing public health issue in the region, especially given that PM 2.5 is capable of penetrating deep into the lung tissue and precipitating a number of respiratory diseases.3 Japan was also severely affected during its period of accelerated economic growth in the wake of post-war reconstruction in the 1960s, with both air pollution and the prevalence of respiratory diseases rising markedly. In Kurashiki, a city located in the Okayama Prefecture, there were reports of pulmonary toxicity owing to oxidant air pollutants rising by a factor of 1.73 among the city's inhabitants in the period leading up to 1970 as yearly average SO3 levels increased. The majority of pollution-related deaths in this period was due to acute exacerbation of asthma. Although patients do not commonly recover fully from pollution-related respiratory diseases, FEV1/FVC ratios (calculated by dividing FEV1 by FVC) may return to within the normal range once air quality is improved.4 As a result, Japan passed the Pollution-Related Health Damage Compensation Law in 1973 with the aim of identifying designated air pollution victims within affected areas for compensation. Patients with a diagnosis of bronchial asthma, chronic bronchitis or pulmonary emphysema and who had been resident in any designated air pollution zone for a specified period of time were legally recognised as pollution victims. These designated victims were fully reimbursed the costs of all related medical treatment by the state. However, patients' lung function, as measured using FEV1/FVC ratios, was not among the diagnostic criteria used to determine eligibility for compensation, as no agreed clinical definition for chronic obstructive pulmonary disease (COPD) existed at that time. Pollution is known to cause and exacerbate a number of chronic respiratory diseases. The World Health Organisation has placed air pollution as the world's largest environmental health risk factor. There has been recent publicity about the role for diet and anti-oxidants in mitigating the effects of pollution, and this review assesses the evidence for alterations in diet, including vitamin supplementation in abrogating the effects of pollution on asthma and other chronic respiratory diseases. We found evidence to suggest that carotenoids, vitamin D and vitamin E help protect against pollution damage which can trigger asthma, COPD and lung cancer initiation. Vitamin C, curcumin, choline and omega-3 fatty acids may also play a role. The Mediterranean diet appears to be of benefit in patients with airways disease and there appears to be a beneficial effect in smokers however there is no direct evidence regarding protecting against air pollution. More studies investigating the effects of nutrition on rapidly rising air pollution are urgently required. However it is very difficult to design such studies due to the confounding factors of diet, obesity, co-morbid illness, medication and environmental exposure.Pharmacotherapy for Respiratory Disorders Essay Paper Tobacco smoke has been shown to contain high levels of PM 2.5, and is likely to be associated with many health issues in common with air pollution. Tobacco use has been shown to reduce lung function, as measured using FEV1/FVC ratios, and has also been identified as a cause of COPD and other tobacco-related diseases. The WHO Framework Convention on Tobacco Control was therefore adopted in 2003.5 However, tobacco use remains a significant public health issue. According to a WHO report, more than 1.1 billion people globally are regular smokers.6 Furthermore, Asia accounts for a third of the total world cigarette consumption, and there has been a local rise in air pollution.7 Both air pollution and tobacco smoke have been shown to reduce patients' FEV1/FVC ratios, to increase the risk of obstructive ventilatory defects and to exacerbate existing respiratory symptoms. Tanaka et al4have reported that when air quality is improved, the annual change in patients' FEV1 can return to within the normal range. However, the association of ongoing tobacco use with respiratory function and pulmonary symptoms in patients with already reduced FEV1/FVC ratios resulting from bronchial hypersensitivity due to air pollution has not yet been elucidated. For this analysis of national registry data, we defined comparator countries as the EU15+ countries (excluding the UK). Previous reports have used the EU15+ countries as an appropriate comparator group for health issues in the UK because of similar or higher health expenditure in these countries.8 This group of countries included the EU member states before May 2004, not including the UK (that is, Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, and Sweden), as well as Australia, Canada, the US, and Norway. We obtained data for respiratory disease mortality for the countries of interest from the WHO Mortality Database.9 The database contains country level data for deaths by age, sex, and cause of death from 1955 onwards, as reported annually by WHO member states from their local death registration systems. Data are reported as crude mortality in each country per year. For each country and year, we grouped data within the age groups provided by the World Standard Population, stratified by sex. We then calculated age standardised death rates per 100 000 people in the specific age group by using population data and the World Standard Population.10We included data from 1985 to 2015 as these were the most recent data available for most countries. Almost complete data were available for each country studied with a total of 30 of 570 (5%) missing data elements across all countries over the observation period.Pharmacotherapy for Respiratory Disorders Essay Paper Diagnostic categories We included the following ICD (international classification of diseases) categories of respiratory diseases: infectious (including respiratory tuberculosis, influenza, and viral and bacterial pneumonias), neoplastic (including malignancy of trachea, bronchus, lung, and pleura), interstitial (including idiopathic pulmonary fibrosis, and unspecified interstitial lung diseases), obstructive (including asthma, chronic obstructive pulmonary disease, and bronchiectasis), and other (including pneumothorax, pulmonary oedema, and other unspecified respiratory disorders). A list of the ICD-9 and ICD-10 codes (9th and 10th revisions, respectively) used in this analysis is provided in supplementary table 1. We used both ICD-9 and ICD-10 codes for overall respiratory disease covering the period 1985 to 2015. We used ICD-10 codes for the analysis of subcategories of respiratory disease covering the period 2001 to 2015. This was decided a priori to prevent introduction of discrepancies through coding changes. Statistical analysis We computed age standardised death rates for respiratory disease mortality in the UK and computed the median composite age standardised death rate in the remaining EU15+ countries. We tested for significant differences between the UK and EU15+ countries by using mixed effects regression models for change in mortality using the PROC GENMOD procedure in SAS version 9.4. Each model included all available data years for all countries with estimates for individual country intercepts. We constructed a model which included predictor terms: country (UK or EU15+), year, and the interaction of country with year. We used auto regression to account for within country correlations. The outcome variable was the log of mortality. The coefficient results of this model multiplied by 100 are interpreted as symmetric percentage differences.11 Significance in the models was defined as P<0.05. We used locally weighted scatter plot smoother to assess trends in mortality from overall respiratory disease as well as subcategories of respiratory diseases.Pharmacotherapy for Respiratory Disorders Essay Paper Secondly, we repeated the same modelling strategy for repeated measures by using subcategories of respiratory diseases (infectious, neoplastic, interstitial, obstructive, and other) to compare trends between the UK and EU15+ countries. Whereas our analysis of overall respiratory disease mortality assessed trends over a 30 year period by using both the ICD-9 and ICD-10 classification systems, we chose a priori to analyse the subcategories of respiratory disease mortality by using the ICD-10 classification system to ensure maximum comparability of disease coding. We grouped mortality by ICD-10 chapter. For this analysis, we computed age standardised death rates in each subcategory of respiratory disease and constructed data series plots for graphical inspection. Owing to the risk of multiple testing, we corrected using the Bonferroni method the level of significance for the five subcategories of respiratory disease, giving P<0.01 as statistically significant for the subgroup analyses. Sensitivity analysisWe performed one post hoc confirmatory analysis. For data deposited in the WHO Mortality Database, the preferred sources of information are death registration data, including medical certification of the cause of death and cause of death coded by using ICD categories. One possible explanation for the observed greater mortality in the UK than in EU15+ countries could include differences in medical certification and hospital discharge coding practices between comparator countries. Therefore, after completing the primary analysis to compare respiratory disease mortality, we considered the possibility that differences between health systems for death registration could contribute to the overall differences between the UK and EU15+ countries. We performed a post hoc sensitivity analysis to investigate this possibility and, for this analysis, we assessed trends in mortality for other common broad disease categories, including cardiovascular and cerebrovascular diseases, as well as renal diseases, and compared age standardised death rates for each category of disease. This sensitivity analysis, therefore, compared the UK with EU15+ countries for non-respiratory diseases to consider the possibility that coding practices alone might have contributed to the observed difference in respiratory disease mortality.Pharmacotherapy for Respiratory Disorders Essay PaperCommon Types of Respiratory Medications Used for Treating Breathing ProblemsRespiratory medicines are designed to assist you breathe better while treating different kinds of breathing problems such as wheezing and respiratory shortness. These include inhaling medications with nebulizer devices in a mist-like form. Various kinds of medicines can be recommended by doctors for the treatment of chronic obstructive pulmonary disease (COPD), cystic fibrosis, asthma and more. These include the following:Antimicrobial medicationsThese are used for the treatment of breathing infections. These medicines include tobramycin (TOBI), ribavirin (Virazole), pentamidine (Nebupent) etc. Such kinds of medicines are used for managing breathing infections.CorticosteroidsThese are actually a type of steroids which are designed to reduce swelling in the airways. One of the most well-known instances of Corticosteroids is Budesonide (Pulmicort Respules).Bronchodilator medicationsThese are used in order to open and relax the air passages. Metaproterenol (Alupent) and ipratropium (Atrovent) are two of the common examples of these drugs.Short-acting beta agonistsThese are actually a type of bronchodilators which can open as well as relax airways which have got narrowed down. Levalbuterol HCl (Xopenex) and albuterol sulfate (AccuNeb) are some of the instances of this group of drugs.Long-acting beta agonistsThese kinds of bronchodilators can be used along with inhaled corticosteroids. Formoterol (Perforomist) and arformoterol (Brovana) are two instances of these medicines. Doctors can prescribe these with inhaled corticosteroids as a combination in their prescription for respiratory disorder patients.Racemic epinephrineThese are used for treating croup, severe attacks of asthma and other emergency respiratory cases.MucolyticsSuch kinds of drugs are used for thinning, loosening and clearing out secretions of mucus from lungs. Dornase alfa (Pulmozyme) and acetylcysteine (Mucomyst) are two of the major examples of these medicines.Pharmacotherapy for Respiratory Disorders Essay PaperCombination medicationsAlbuterol (DuoNeb) / ipratropium are the combination drugs which are generally found to be very useful for alleviating respiratory symptoms. These assist in reducing swelling of the airways.IV antibioticsThese can be used for the treatment of acute cases of infection, such as bacterial pneumonia or bacterial bronchitis. These are used in an intravenous manner for curing the respiratory problems of patients.Supplemental oxygenIt can be used for raising the level of oxygen in bloodstream. Doctors can recommend some steps for the treatment of thick mucus, wheezing, coughing, shortness of breath and inflammation in the air passage. Some methods can be taught by a nurse or a respiratory therapist to show you the ways of conducting those at home.The pharmaceutical industry is constantly developing new medications for patients with respiratory conditions, and while that is certainly a good thing, it can leave respiratory therapists feeling as if they are always playing catch up.What do AARC members do to stay informed about the respiratory medications prescribed for their patients? We asked members of the AARC's Specialty Sections to weigh in.Additional resourcesLisa Pisarek, RRT, CPFT, considers herself lucky when it comes to obtaining information about new medications. As a member of a busy physician practice, she benefits from the many drug reps that come by to speak to the physicians."I also work per diem in a local community hospital," she said. "My fellow staff at the hospital are often unfamiliar with new inhalers that I am fortunate to already know all about."Michael McPeck, RRT, FAARC, is a specialist in aerosol science, but even he finds it hard to keep up with new medications. First, there are so many coming on the market, and second, so many of them now come with their own dedicated delivery device.He taps into his professional contacts, pharma marketing, and online sources to remain on track. Two web-based resources he recommends are Orally Inhaled Nasal Drug Products, a weekly subscription blog and website, and Inhalation Drug Delivery Specialist, which operates on LinkedIn.The web is the go-to place for new drug info for John Rivituso, RRT-NPS, CPFT, as well."There is a site called First Word that I receive emails from every day," Rivituso said. "It's free and has updates on the pharma industry, including drugs that have received FDA approval and those that have not."Robert Erickson, RRT-NPS, RPFT, looks to his professional organizations and other well-known sources to remain current."In addition to being a 40+ year member of the AARC, I am an allied member of the ACCP and an avid reader of the pulmonary section of Medscape," Erickson said. "These two additional resources keep me ahead of the curve and keep the staff ready for new inhaled drugs in the pipeline."He helps his staff and the students who rotate through his department stay up to date by preparing an abbreviated drug sheet that provides them with a quick way to review the latest medications.Pharmacotherapy for Respiratory Disorders Essay Paper Aids to smoking cessation Smokers should be strongly encouraged to stop; smoking cessation advice and support, together with various pharmaceutical products are available for those who wish to do so. Nicotine replacement allows some individuals to ease the effects of tobacco withdrawal. Nicotine can be administered in various forms, including lozenges, gum, transcutaneous patches and by inhalation. Pharmaceutical agents with demonstrable benefits in selected individuals include bupropion, originally an antidepressant, and varencicline, a selective nicotine receptor agonist. Bronchodilators Bronchodilators vary in both their mode and duration of action and they can be administered by various routes. The commonly used inhaled bronchodilators are listed in table 1. All are aimed essentially at relaxing the smooth muscle of the airway wall and they are very widely used, both in adults and children, either as sole or adjunctive treatment for asthma and chronic obstructive pulmonary disease (COPD), and for other conditions characterised by diffuse airway narrowing, e.g. bronchiectasis.Among the most frequently used bronchodilators are the β-sympathomimetic agonists, which mimic the action of the sympathetic nervous system by selectively stimulating the β2receptors on bronchial smooth muscle. They are most commonly administered via inhalation, traditionally from a metered-dose inhaler (MDI). However, careful attention to inhaler technique is important, as many individuals experience difficulty in coordinating the manoeuvres necessary for effective inhalation with the traditional 'press and breathe' inhaler. Detailed guidance on the available inhaler devices and their use has recently been published by a task force set up jointly by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM). Devices used to overcome problems with inhaler technique include inhalation via a 'spacer' (figure 1a) and breath-activated inhalers (figure 1b). Alternatively, the drug can be inhaled as a very fine dry powder (dry powder inhaler (DPI)) (figure 1c) or as a soft mist (soft mist inhaler (SMI)) (figure 1d). Sometimes (during an acute asthma attack, for example) larger doses are inhaled as a nebulised solution driven by a flow of air or oxygen (usually available only in hospital) or by a portable, electrically powered compressor  Pharmacotherapy for Respiratory Disorders Essay PaperShort-acting β2-agonists are a mainstay of treatment for symptomatic relief and for acute exacerbations of asthma and COPD, while longer-acting agents are used on a regular basis to produce background bronchodilatation in patients with chronic airway obstruction, usually in conjunction with an inhaled steroid (table 1).Anti-muscarinic drugs inhibit the action of the parasympathetic nervous system and produce bronchodilatation by reducing the tone of the airway smooth muscle; as with β 2 -agonists (together with which they are often used), both short- and long-acting versions are available. Administration is by inhalation, which avoids the side-effects of widespread parasympathetic inhibition.The methylxanthine bronchodilator drug theophylline is a nonspecific inhibitor of the enzyme phosphodiesterase (PDE). It is administered orally; its more soluble derivative, aminophylline, is given intravenously and has been a traditional method of treating acute asthma attacks. Theophylline is, however, less favoured nowadays as side-effects are frequent and blood level monitoring is desirable for control of the appropriate dose. More recently developed, specific PDE inhibitors include the PDE4 inhibitors (e.g. roflumilast) which have bronchodilator and anti-inflammatory effects in COPD and the PDE 5 inhibitors (e.g . sildenafil) used in the treatment of pulmonary hypertension. Corticosteroids Corticosteroids, such as prednisolone (given orally) or methyl prednisolone (given parenterally), are powerful anti-inflammatory agents used in a wide range of medical conditions. In respiratory practice, steroids are used most commonly by inhalation in the long-term treatment of asthma and COPD. Oral or intravenous steroids are the mainstay of treatment of acute asthma; in most cases, regular treatment for 5–10 days suffices and a similar approach has been shown to hasten recovery in acute exacerbations of COPD.When introduced in the 1970s, inhaled steroids revolutionised the long-term treatment of asthma, as they allowed better control of the condition without the side-effects of oral steroids, which had been widely used previously. Though  less effective than in asthma, regular inhaled corticosteroid treatment has also been shown to benefit patients with severe COPD, by reducing the frequency of exacerbations. An inhaled steroid is usually administered twice daily from an MDI or DPI and, increasingly, a steroid is combined with a long-acting β2-agonist in the same inhaler  Pharmacotherapy for Respiratory Disorders Essay Paper   ORDER  HERE NOW   Category Duration of action Generic name Proprietary name (manufacturer) β2-agonist Short Salbutamol Ventolin (GSK), Airomir (Graceway Pharmaceuticals) Terbutaline Bricanyl (AstraZeneca) Long Salmeterol Serevent (GSK) Formoterol Oxis (AstraZeneca), Foradil (Schering Plough and Novartis), Atimos (Chiesi) Indicaterol Onbrez (Novartis) Antimuscarinic Short Ipratropium Atrovent (Boehringer Ingelheim) Long Tiotropium Spiriva (Boehringer Ingelheim and Pfizer) Corticosteroid Beclomethasone Becotide (GSK), Qvar (Teva), Clenil (Chiesi) Budesonide Pulmicort (AstraZeneca) Fluticasone Flixotide (GSK) Mometasone Asmanex (Merck, Sharpe and Dohme) Ciclesonide Alvesco (Takeda) Compound preparations Salmeterol+fluticasone Seretide (GSK) Formoterol+budesonide Symbicort (AstraZeneca) Table 1 – Commonly used inhaled therapy for asthma and chronic obstructive pulmonary disease. Oral steroids are also used for the longer-term treatment of some types of interstitial lung disease, particularly sarcoidosis, hypersensitivity pneumonitis and some of the interstitial pneumonias. Long-term oral steroid treatment is, however, accompanied by frequent side-effects, against which the benefit of suppressing troublesome symptoms (usually breathlessness) has to be balanced. Antibiotics For respiratory infections, antibiotics can be given either as a short course (5–10 days for acute infective exacerbations of COPD, for example) or on a longer-term basis, particularly for chronic bronchial infection (in cystic fibrosis (CF) or non-CF bronchiectasis, for instance).Ideally, antibiotic treatment is tailored to the specific infecting organism(s), but often, especially in COPD, this may not be apparent or may come to light only after a couple of days when culture results become available; consequently, a broad-spectrum antibiotic is usually prescribed in order to cover the most likely pathogens. Most infective exacerbations of COPD are due initially to viral infection, which is not generally susceptible to conventional antibiotics; however, this is often superseded by bacterial infection, at which stage the sputum becomes purulent and an antibiotic is indicated.Pharmacotherapy for Respiratory Disorders Essay PaperIn nonimmunocompromised patients, less severe community-acquired pneumonia usually responds to a broad-spectrum antibiotic, e.g. one of the β-lactam (penicillin) family. However, combinations of antibiotics are used when pneumonia is more severe and specifically targeted treatment is desirable when the infecting agent is likely to be less susceptible to the commonly used broad-spectrum agents, for instance Mycoplasma pneumoniae, Staphylococcusaureus or Legionella pneumophila (Legionnaires' disease).With chronic bronchial infection, as in CF or bronchiectasis, longer-term antibiotic treatment may be indicated, particularly to control pathogens such as Pseudomonas aeruginosa; some, such as tobramycin, can be given effectively as an aerosol by nebulisation.The treatment of tuberculosis (TB) and related mycobacterial infections requires specific antibiotics, which are given in combination for a prolonged period (at least 6 months for TB and up to 24 months for non-tuberculous mycobacteria). The most frequently used combination for TB comprises isoniazid plus rifampicin for 6 months, supplemented by pyrazinamide and ethambutol for the first 2 months. Identifying the drug sensitivity of the infecting organism is particularly important due to the increasing frequency of drug-resistant strains. Other drugs Diuretics Diuretics are frequently used in patients with chronic fluid retention ('cor pulmonale') due to severe pulmonary hypertension, either primary or secondary to advanced COPD. Anticoagulation and thrombolytic agents Anticoagulation is the usual primary treatment in acute pulmonary embolism, with thrombolytic agents used if embolism is sufficiently extensive to compromise cardiac output. Vasodilators Specific vasodilator and other drugs are increasingly used to improve the pulmonary circulation in patients with primary pulmonary hypertension. Mucolytic drugs Mucolytic drugs, such as carbocisteine and dornase alpha (DNAse) reduce the viscosity ('stickiness') of sputum and aid expectoration, e.g. in CF, where they may reduce the frequency of acute exacerbations. Mucolytic drugs may also reduce the frequency of exacerbations in COPD. Cytotoxic drugs Cytotoxic drugs are used in the treatment of lung cancer and mesothelioma. Although not likely to be curative, some agents, usually in combination, prolong average life-expectancy in small cell lung cancer and they are increasingly used as palliative treatment of nonsmall cell lung cancer.Some cytotoxic drugs are also useful in the treatment of certain types of interstitial diseases and pulmonary vasculitis; for example, cyclophosphamide in granulomatosis with polyangiitis (Wegener's). Tumour growth modifiers Biological therapy with drugs such as those that inhibit the enzyme tyrosine kinase is effective against cancers that express certain genes (e.g. the epidermal growth factor receptor); this type of 'tailored' approach to certain lung cancers offers hope for greater therapeutic success in future. Comorbidity Many patients with respiratory disease also require medication for comorbid disease: for instance, in cases of coexisting ischaemic heart disease and COPD, which are common comorbidities due to their shared smoking aetiology.Pharmacotherapy for Respiratory Disorders Essay Paper Nonpharmacological therapy Oxygen Oxygen is widely used in patients with advanced respiratory disease, both in hospital and, on a long-term basis, in the patient's home. Indications include both the relief of symptoms and prolongation of survival. In general, oxygen is only likely to be beneficial when the level of oxygen in the arterial blood (arterial oxygen tension (PaO2)) is low; it is not a general panacea for breathlessness, as this often results from factors other than shortage of oxygen. Therefore, accurate assessment is essential before oxygen is prescribed; this includes confirmation of hypoxaemia when the patient  is breathing air and demonstration of improvement when breathing oxygen.Several different methods for administering oxygen are available (figure 2). The optimal method for an individual patient depends on the nature and severity of the underlying condition, as well as the situation in which oxygen is to be used. In very ill patients in hospital with severe hypoxaemia (e.g. in acute respiratory distress syndrome, extensive pneumonia or severe acute asthma), high-flow oxygen, via  a face mask or in conjunction with assisted ventilation, may be required. However, in patients with exacerbations of severe COPD, uncontrolled high-flow oxygen can result in progressive retention of carbon dioxide (hypercapnia) and respiratory acidosis, which itself may be life-threatening. In this situation, therefore, it is necessary to restrict the concentration or flow of oxygen being breathed. Low-flow oxygen can be delivered comfortably via small nasal cannulae (figure 2a and 2b), but this does not give precise control of the inspired oxygen concentration. The latter can be controlled by use of a mask that operates on the Venturi principle, where the concentration of oxygen breathed by the patient is relatively independent of the oxygen flow rate. Such masks allow only a small increase of inspired oxygen concentration – for example to 24% or 28%, compared to the 21% present in room air – but in COPD this is usually sufficient to relieve life-threatening hypoxaemia, while at the same time minimising the risk of serious hypercapnia.Long-term oxygen at home has been shown to improve the life-expectancy of patients with severe hypoxaemia resulting from advanced COPD. To achieve this, oxygen treatment needs to be given for as long as possible each day (minimum: average 15 out of 24 hours). It is delivered most conveniently by an oxygen concentrator (which, as the name implies, concentrates the oxygen from room air) or by using a large tank of liquid oxygen, from which a small cylinder can be refilled as required. Patients who show worsening oxygenation ('desaturation') during exercise may benefit from breathing oxygen during exertion; this can be supplied by a refillable small liquid oxygen tank or by a portable concentrator.However, even severely hypoxaemic patients may not show desaturation during exercise and so prescription of ambulatory oxygen should be preceded by specialist assessment and the demonstration of both desaturation when breathing room air and improved performance when breathing oxygen. Physiotherapy Physiotherapy is particularly helpful as an aid to clearing bronchial secretions, for example in acute exacerbations of COPD and in patients with chronic production of infected sputum, as in CF and bronchiectasis. Various techniques are used, including postural drainage and forced expiration; often, these are taught to patients who continue to use them regularly at home. Other important aspects of physiotherapy, including exercise and muscle training, are employed as part of pulmonary rehabilitation (see chapter 29). Ventilatory support Intermittent positive pressure ventilation The traditional method of mechanically assisting the ventilation of seriously ill patients in hospital is by intermittent positive pressure ventilation (IPPV), in which the patient's airway is connected to a ventilator that blows air (usually with supplementary oxygen) into the lungs, with the ventilator set to deliver a specified volume or pressure. The air is delivered into the trachea via an endotracheal tube, or if ventilation needs to continue for a prolonged period, via a tracheostomy tube. Modern ventilators are highly sophisticated and allow a range of modes and patterns of ventilation, including total ventilation, in which the machine does all the work, and various 'assist' modes, in which the ventilator detects and then supplements each inspiratory effort. Noninvasive ventilation Over the past 20 years, noninvasive ventilation (NIV) has increasingly been used. It offers several advantages: in particular, the need for sedation is avoided; the patient retains the ability to cough and communicate; and the risk of further infection associated with intubation of the airway is minimised. Ventilation is achieved by delivering air (with or without supplementary oxygen) via a tight-fitting face mask applied to the nose, or nose and mouth (the range of patient 'interfaces' is the same as is used for delivering continuous positive airway pressure (CPAP) for treating obstructive sleep apnoea syndrome (OSAS) – see below). In most respiratory departments, NIV is now first-line management for  patients requiring ventilatory assistance for acute exacerbations of COPD. It is also increasingly used for long-term nocturnal domiciliary ventilation in certain groups of patients with chronic hypercapnia. It is particularly suitable and effective for chronic respiratory failure due to severe respiratory muscle weakness (e.g. various muscular dystrophies or motor neurone disease/amyotrophic lateral sclerosis) or severe deformity of the chest wall (e.g. scoliosis). Long-term domiciliary NIV is also used in some patients with severe COPD, but its indications in this condition require further investigation.Pharmacotherapy for Respiratory Disorders Essay Paper Continuous positive airway pressure CPAP is a simpler form of ventilatory support, which is used with one of two aims. CPAP delivered by a conventional ventilator is used in the management of very ill patients with severe hypoxaemia, as applying a continuous inflating pressure to the airway (in addition to the fluctuating pressure required to ventilate the lungs) increases lung volume, which is beneficial in improving oxygenation.In its alternative, and now much more common, application, CPAP is used as the treatment of choice in most patients with symptomatic obstructive sleep apnoea syndrome (OSAS) in order to overcome the narrowing or obstruction of the upper airway (pharynx), which is the prime mechanism of OSAS. In this situation, applying a positive pressure at the nose or mouth (or both) during sleep stabilises the upper airway; maintaining airway patency in this way prevents the recurrent apnoeas and the accompanying hypoxaemia and sleep disturbance which they cause. The pressure delivered is adjusted either manually or automatically to the level necessary to maintain the patency and stability of the airway and the patient is encouraged to use this treatment every night, usually indefinitely. Although some individuals experience discomfort or intolerance, the majority find that the improvement in daytime alertness, which is often dramatic, more than compensates for this. A variety of patient interfaces is available by which the pressure is delivered, via the nose or mouth or sometimes both (figure 3 – see also chapter 23). Radiotherapy In a minority of patients with nonsmall cell bronchial carcinoma, radical radiotherapy is used with the aim of achieving a cure. This approach is only appropriate for patients with small peripheral tumours, with no evidence of spread, and in whom surgical resection is not an option. The direction of the radiation beam can be focused more precisely by use of stereotactic methods of three-dimensional imaging.More commonly, radiotherapy is used, sometimes in combination with chemotherapy, in both small and nonsmall cell bronchial carcinoma, with the aim of achieving a partial or, occasionally, complete response, and also as palliative treatment to improve symptoms, particularly haemoptysis or pain due to bone invasion or metastasis. Thoracic surgery Surgical treatment is used for both malignant and nonmalignant respiratory disease. It is the treatment of choice for primary nonsmall cell bronchial carcinoma, and gives the best prospect of cure when the tumour appears technically resectable, there is no evidence of metastasis and the patient is fit for the procedure. Depending on the extent and position of the cancer, resection may involve removal of a whole lung (pneumonectomy), one or more lobes (lobectomy) or, less commonly, a lung segment (segmentectomy).Surgical treatment options for other respiratory conditions include: removal of benign tumours or of giant bullae; lung volume reduction surgery for selected patients with severe hyperinflation of the lungs due to emphysema; resection of lung abscess, severe localised bronchiectasis or lung affected by drug-resistant TB; and pleural surgery for empyema, persistent pneumothorax or extensive pleural thickening. The ultimate form of surgical treatment is lung transplantation, which is performed for a variety of end-stage lung diseases, most commonly nowadays for advanced CF.Further information can be found in chapter 32.Pharmacotherapy for Respiratory Disorders Essay Paper Chronic obstructive pulmonary disease (COPD) is a group of progressive lung diseases that make it difficult to breathe. COPD can include emphysema and chronic bronchitis.If you have COPD, you may have symptoms such as trouble breathing, cough, wheezing, and tightness in your chest. COPD is often caused by smoking, but in some cases it's caused by breathing in toxins from the environment.There is no cure for COPD, and the damage to the lungs and airways is permanent. However, several medications can help reduce inflammation and open your airways to help you breathe easier with COPD. Short-acting bronchodilators Bronchodilators help open your airways to make breathing easier. Your doctor may prescribe short-acting bronchodilators for an emergency situation or for quick relief use as needed. You take them using an inhaler or nebulizer.Examples of short-acting bronchodilators include: albuterol (Proair HFA, Ventolin HFA) levalbuterol (Xopenex) ipratropium (Atrovent HFA) albuterol/ipratropium (Combivent Respimat) Short-acting bronchodilators can cause side effects such as dry mouth, headache, or cough. These effects should go away over time. Other side effects include tremors (shaking), nervousness, and a fast heartbeat.If you have a heart condition, tell your doctor before taking a short-acting bronchodilator. Corticosteroids With COPD, your airways can be inflamed (swollen and irritated). Inflammation makes it harder to breathe. Corticosteroids are a type of medication that reduces inflammation in the body, making air flow easier in the lungs.Several types of corticosteroids are available. Some are inhalable and should be used every day as directed. They're usually prescribed in combination with a long-acting COPD drug.Other corticosteroids are injected or taken by mouth. These forms are used on a short-term basis when your COPD suddenly gets worse.The corticosteroids doctors most often prescribe for COPD are:Pharmacotherapy for Respiratory Disorders Essay Paper Fluticasone (Flovent), which comes as an inhaler that you use twice daily. Side effects can include headache, sore throat, voice changes, nausea, cold-like symptoms, and thrush. Budesonide (Pulmicort), which comes as a handheld inhaler or for use in a nebulizer. Side effects can include colds or thrush. Prednisolone, which comes as a pill, liquid, or shot. It's usually given for emergency rescue treatment. Side effects can include headache, muscle weakness, upset stomach, and weight gain. Methylxanthines For some people with severe COPD, the typical first-line treatments, such as fast-acting bronchodilators and corticosteroids, don't seem to help when used on their own.When this happens, some doctors prescribe a drug called theophyllinealong with a bronchodilator. Theophylline works as an anti-inflammatory drug and relaxes the muscles in the airways. Theophylline comes as a pill or liquid you take daily.Side effects of theophylline can include nausea or vomiting, tremors, headache, and trouble sleeping. Long-acting bronchodilators Long-acting bronchodilators are medications that are used to treat COPD over a longer period of time. They're usually taken once or twice daily using inhalers or nebulizers.Because these drugs work gradually to help ease breathing, they don't work as quickly as rescue medication. They're not meant to be used in an emergency situation.The long-acting bronchodilators available today are: aclidinium (Tudorza) arformoterol (Brovana) formoterol (Foradil, Perforomist) glycopyrrolate (Seebri Neohaler) indacaterol (Arcapta) olodaterol (Striverdi Respimat) salmeterol (Serevent) tiotropium (Spiriva) umeclidinium (Incruse Ellipta) Side effects of long-acting bronchodilators can include: dry mouth dizziness tremors runny nose irritated or scratchy throat upset stomach More serious side effects include blurry vision, rapid or irregular heart rate, and an allergic reaction with rash or swelling.Pharmacotherapy for Respiratory Disorders Essay Paper Combination drugs Several COPD drugs come as combination medications. These are mainly combinations of either two long-acting bronchodilators or an inhaled corticosteroid and a long-acting bronchodilator.Combinations of two long-acting bronchodilators include: glycopyrrolate/formoterol (Bevespi Aerosphere) glycopyrrolate/indacaterol (Utibron Neohaler) tiotropium/olodaterol (Stiolto Respimat) umeclidinium/vilanterol (Anoro Ellipta) Combinations of an inhaled corticosteroid and a long-acting bronchodilator include: budesonide/formoterol (Symbicort) fluticasone/salmeterol (Advair) fluticasone/vilanterol (Breo Ellipta) Roflumilast Roflumilast (Daliresp) is a type of drug called a phosphodiesterase-4 inhibitor. It comes as a pill you take once per day.Roflumilast helps relieve inflammation, which can improve air flow to your lungs. Your doctor will likely prescribe this drug along with a long-acting bronchodilator.Side effects of roflumilast can include: weight loss diarrhea headache nausea cramps tremors insomnia You should also tell your doctor if you have liver problems or depression before taking this medication. Asthma is the most prevalent chronic disease of childhood, and it causes significant morbidity and mortality in both adults and children. About 235 million adults and children worldwide have asthma.4 In the United States, asthma affects 8% of adults (18.7 million) and 9.3% of children (6.8 million).5 Asthma is the primary diagnosis for 14.2 million physician office visits, 1.8 million emergency department visits, and 3345 deaths annually.5 Asthma is also a significant economic burden in the United States, with costs totaling nearly $60 billion annually.6 Prescription medications are the single largest direct medical expenditure and account for 71% of direct medical costs.6 Asthma results from a complex interaction of genetic and environmental factors. There appears to be an inherited component because the presence of asthma in a parent is a strong risk factor for developing asthma in a child. This risk increases when a family history of atopy is also present. The presence of atopy is a strong prognostic factor for continued asthma as an adult. Environmental exposure also appears to be an important etiologic factor. Although asthma occurs early in life for most patients, those with occupational asthma develop the disease later upon exposure to specific allergens in the workplace. Exposure to secondhand smoke after birth increases the risk of childhood asthma.7 Adult-onset asthma may be related to atopy, nasal polyps, aspirin sensitivity, occupational exposure, or recurrence of childhood asthma. Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. In addition to generating high healthcare costs, COPD imposes a significant burden in terms of disability and impaired quality of life. Unlike many leading causes of death and disability, COPD is projected to increase in many regions of the world as the frequency of smoking is rising and the population is aging. The pharmacological treatment of COPD includes bronchodilators to relax smooth muscle, such as β2-agonists (salbutamol, terbutaline, and fenoterol, short-acting β2-agonists as well as salmeterol, formoterol, and indacaterol, and long-acting β2-agonists) and anticholinergics, such as ipratropium, oxitropium (short-acting anticholinergic), and tiotropium (long-acting anticholinergic). Although airway inflammation in COPD poorly responds to steroids, several inhaled corticosteroids (fluticasone, budesonide, and beclomethasone) are in use in combination with long-acting β2-agonists. Other medications include theophylline (both a bronchodilator and a phosphodiesterase inhibitor) and the phosphodiesterase-4 antagonists, such as roflumilast. Finally, a number of novel long-acting anticholinergics and β2-agonists with once- or twice-daily profiles are in development and clinical testing.Pharmacotherapy for Respiratory Disorders Essay Paper Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airway inflammation, a decline in lung function over time, and progressive impairment in quality of life. The disease has relatively high prevalence rates worldwide (5–13%) [1, 2] and is mainly caused not only by the inhalation of noxious substances, predominantly cigarette smoking in the Western world, but also by indoor air pollution, particularly in the developing countries.COPD is associated with high mortality and morbidity rates and a high economic and social burden, mainly due to the requirement for substantial and ongoing medical support [3, 4]. COPD is the fourth leading cause of death worldwide and is expected to be the third leading cause by 2030 [5]. It is generally believed that despite the availability of both national and international guidelines, COPD remains substantially underdiagnosed and undertreated and is rarely regarded as a health issue of top priority.For many years, smoking cessation has been known to be the single effective intervention for reducing the risk of developing COPD and slowing its progression down [6]. However, recent data from long-term trials have shown that initiating maintenance pharmacological treatment at early stages of the disease, when there is an opportunity to alter the progression of the disease and maximize patient benefit, may alter the clinical course of COPD and can be more effective than at later stages of the disease [7, 8]. Moreover, it has been demonstrated that despite the relative steroid insensitivity of airway inflammation in COPD, the combination of long-acting bronchodilator therapy with inhaled glucocorticosteroids (ICS) is beneficial for patients with severe COPD [9, 10]. Thus, early and optimal pharmacotherapy appears to be fundamental in the management of COPD.The aim of this paper is to summarize briefly the pharmacotherapy of stable COPD and to give an overview of the pharmacological profile of these medications. 2. Overview of Pharmacological Treatment in COPD In stable COPD pharmacotherapy is used to relieve symptoms, reduce the frequency and severity of acute exacerbations, reduce disease progression and mortality, and improve health status and increase exercise tolerance.Previously, it has been conceptualized that COPD treatment should follow a stepwise approach, depending exclusively on disease severity as assessed by spirometry. Initially in mild (stage I) COPD, active risk reduction should be pursued with the addition of short-acting bronchodilators as-needed. As the disease progresses and lung function declines (stage II–IV) regular (maintenance) treatment with one or more long-acting bronchodilators, such as a long-acting muscarinic antagonist (LAMA; also known as a long-acting anticholinergic) or long-acting -agonist (LABA), should be introduced alone or in combination with ICS.More recently, data about the clinical presentation of COPD have resulted in anewclassification of thedisease. As highlighted in the latest version of the GOLD document, airflow limitation (FEV1) alone is a poor descriptor of the disease status, and therefore the degree of airflow limitation has been amended by symptoms and exacerbation rate [11]. Four categories (A–D) have been established in which patients can be enrolled based on symptoms' scores and exacerbation history. Moreover, a model for initial pharmacological management has been proposed for each category allowing a more individualized treatment option for each subject.Beside the medications mentioned above, a number of other agents are used in the management of COPD, including mucolytics and methylxanthines. Nonetheless, most guidelines do not currently recommend the widespread use of these agents. Finally, it should be noted that each treatment regimen needs to be patient-specific, especially in older people where severe comorbidities are more common.The method of delivery is an important factor in the prescription of all medications in COPD. In general, inhaled therapy is preferred. For theophyllines, which are given orally, blood levels should be frequently checked as a result of the higher incidence of adverse effects which occur by the use of the oral route.A variety of inhaler devices are available, and the delivery of the drug to the lung depends on devices and techniques. Dry powder inhalers (DPIs) may be more convenient and possibly provide improved drug deposition in COPD patients when compared with simple metered-dose inhalers (MDI) [12]. Nonetheless, the issue is somewhat controversial, and deposition depends also on the available inspiratory flow (acceleration) depending on the severity of COPD. Nebulizer solutions, on the other hand, may be better for those who are severely overinflated and consequently may have low inspiratory flow rates. There is evidence that a significant proportion of patients have problems with inhaler technique [13], and therefore, the prescribing physician must ensure that the patient is taught how to use the prescribed device and that their technique is checked periodically. 3. Bronchodilators Medications that increase the forced expiratory volume in 1 sec (FEV1) or improve other spirometric parameters, usually by altering airway smooth muscle tone, are termed bronchodilators. The use of bronchodilators is one of the key elements in the treatment of COPD, although there is often limited reversibility of airflow obstruction. Nevertheless, the regular use of bronchodilators significantly contributes to many other goals of treatment (see above), especially to symptoms' relieve and improvement of health-related quality of life.Three types of bronchodilator are in common clinical use: (1) -adrenoceptor agonists, (2) anticholinergic drugs, and (3) methylxantines. Bronchodilators are given either on an as-needed basis or on a regular basis. There is evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting agents. 3.1. -Receptor Agonists The principal action of -receptor agonists is to relax airway smooth muscle by stimulating -adrenergic receptors, which increases the intracellular concentration of cyclic adenosine monophosphate (cAMP) and activates protein kinase A. In human airways, -adrenergic receptors are all -receptors. In asthma, -agonists are the most effective bronchodilators available. In COPD the degree of functional reversibility in response to bronchodilators is variable. There is some evidence that patients, who respond better to -agonists, may have more eosinophilic cells in their sputum and exhibit elevated fractional exhaled nitric oxide (FENO) concentration in exhaled breath [14]. These patients are often considered to have an "asthmatic" phenotype.Short-acting inhaled -agonists such as salbutamol, terbutaline, and fenoterol have a relatively rapid onset of bronchodilator effect, which usually wears off within 4–6 hours [15]. Salbutamol is almost 30 times as much selective for  receptors as for  [15]. Its R-isomer is mainly responsive for bronchodilatation when used as an aerosol. Salbutamol is hydrolyzed in tissues and blood to yield the active compound, such as colterol. Over 70% of the inhaled drug is excreted in the urine within three days. Salbutamol is also accessible in tablets, as well as formulations for intramuscular and intravenous applications. Terbutaline is also relatively selective on -receptors (such as on -receptors of bronchial, vascular, and uterine smooth muscles). Terbutaline is also used intravenously to relax smooth muscles and inhibit uterine contractions. Finally, levalbuterol is another effective short-acting bronchodilator that can be applied in COPD patients. Salbutamol and levalbuterol are chemically identical except that they are different enantiomers.LABAs such as salmeterol and formoterol are formulated for twice-daily dosing, have a duration of effect of 12 hours or more with no loss of effectiveness overnight or with regular use in COPD patients [16, 17]. These agents have been shown to reduce the need for rescue medication, improve symptoms and patient-related outcomes, and have a favorable safety profile [18, 19]. Formoterol has a faster onset of action than salmeterol [20], which may be relevant to some patients, especially for morning symptoms. Arformoterol, the (R,R)-enantiomer of formoterol, can be an effective alternative for patients who cannot use conventional inhaler devices, since this drug is available as a nebulized solution.Salmeterol is not used to relieve a COPD attack that has already started [15]. As its dose is low, systemic level of salmeterol is either undetected or very low. A dose of about 12 μg of formoterol has the effect of 50 μg of salmeterol. Salmeterol is metabolized by cytochrome P450 3A4 to α-hydroxysalmoterol, while formoterol is O-demethylated by various CYP enzymes (cytochrome P450 2D6, 2C9, and 2C19, 2A8). Finally, it should be noted that the disease-modifying properties of LABAs are still controversial. These agents improve lung functions, dyspnoea, health-related quality of life, and exacerbation rate but may have no effect on rate of decline in lung function and mortality.Indacaterol, a novel -agonist approved already by both the EMA and the FDA for the treatment of COPD, is currently the only once-daily LABA available for this disease. Since the lung function improvement achieved by indacaterol appears to be slightly better compared to other twice-daily LABAs [21], indacaterol could become a highly effective therapeutic option for the maintenance treatment of COPD. Metabolism of indacaterol was hydroxylation on benzylic carbon, glucuronidation, and oxidative cleavage [15]. Mode of administration, chemical structure, lipophilicity (), and half time of elimination  Pharmacotherapy for Respiratory Disorders Essay Paper 3.2. Anticholinergics The most important effect of anticholinergic medications, such as ipratropium, tiotropium, and oxitropium bromide appears to be blockade of the action of acetylcholine on M3 receptors [22]. Current short-acting drugs also block M2 receptors and modify transmission at the preganglionic junction, although these effects may be less important in COPD. Ipratropium is probably the most frequently used short-acting anticholinergic drug at present. Although it improves lung function and quality of life of COPD patients, the rate of lung function decline, as a hallmark of COPD, may not be affected by ipratropium treatment [22]. In general, the bronchodilating effect of short-acting inhaled anticholinergics lasts longer than that of short-acting -agonists, with some bronchodilating effect lasting up to 8 hours after administration.Tiotropium is the only LAMA currently licensed for use in COPD [23]. Tiotropium has been formulated for once-daily dosing, providing 24-hour bronchodilation, and has a selectivity for M1 and M3 receptors. The clinical database for tiotropium has confirmed an excellent clinical profile for this agent, including symptom improvement, decreased hyperinflation, reduced dyspnea, and improved quality of life [24, 25]. Moreover, treatment with tiotropium reduces the frequency of exacerbations [26] and improves the effectiveness of pulmonary rehabilitation [27]. Therefore, tiotropium is generally recommended for the treatment of all symptomatic patients requiring maintenance treatment.Nevertheless, in recent years some concerns have been raised about tiotropium's safety. In particular, disparate sources have identified stroke and cardiovascular events as possible adverse outcomes. In 2008, Singh et al. published a meta-analysis of 17 randomized clinical trials evaluating the cardiovascular risk associated with inhaled anticholinergic agents [28]. Authors concluded that the use of these drugs was associated with a significantly increased risk of major adverse cardiovascular events, including death from cardiovascular causes, myocardial infarction, and stroke. In contrast, the UPLIFT trial did not show an increased risk of myocardial infarction, death from cardiovascular causes, or death from any cause in its comparison of tiotropium with placebo [29]. Disparate results were then discussed in several forums. Finally, the FDA concluded that because of the strength of the UPLIFT data, the absence of strong signal related to stroke or cardiovascular events with tiotropium, and the potential methodological limitations of the meta-analysis of Singh et al. [28], the current data do not support the assumption of increased risk of stroke, heart attack, or death associated with tiotropium treatment [30].Combining bronchodilators with different mechanisms and durations of action may increase the degree of bronchodilation for equivalent or lesser side effects. For example, a combination of a short-acting -agonist and an anticholinergic produces greater and more sustained improvements in FEV1 than either drug alone [31]. Similarly, the addition of an LABA to an LAMA has been shown to be more effective than either agent alone, without increased side effects [32] and is now included as an option for patients who fail in long-acting bronchodilator monotherapy in most guidelines. Patient involvement To better understand the direct implications of this work on patient knowledge and experience across health systems, we presented our findings to patients with a variety of chronic lung conditions from countries used in this investigation. Specifically, we circulated the results of the current investigation to a total of six patients among the network of the European Federation of Allergy and Airways Diseases Patients Associations and the European Lung Foundation: three with Bronchiectasis (two from the UK, one from the Netherlands), two with Asthma (one from the UK, one from the Netherlands), as well as one with idiopathic pulmonary fibrosis (from Ireland). Patients were asked to comment on the potential implications of this research as well as areas of focus for future research. Patients responded to four questions: all questions were equal to every patient although everyone responded according to their experience, their national healthcare system, and their disease. Responses from patients are summarised as a general answer (non-disease specific) Pharmacotherapy for Respiratory Disorders Essay Paper Respiratory diseases pose a large health burden across health systems and consistently rank among the most fatal diseases across developed countries.1 Chronic obstructive pulmonary disease, lower respiratory tract infections, lung cancer (including tracheal tumours), and tuberculosis have resulted in 2.9 million, 2.4 million, 1.7 million, and 1.2 million deaths, respectively in 2016.1 Poor outcomes from respiratory diseases are consistent across different health systems with lung cancer, chronic obstructive pulmonary disease, and lower respiratory tract infections being consistently leading causes of death. The United Kingdom has previously been highlighted as an outlier with higher mortality and morbidity attributed to respiratory disease than other western countries.2 Previous analysis comparing UK mortality with western Europe, the United States, Canada, and Australia has shown that the UK ranked poorly for respiratory disease.3 When years of life lost were estimated, the UK ranked 17th of 19 for chronic obstructive pulmonary disease and 18th of 19 for lower respiratory tract infections.3 For less common respiratory diseases such as idiopathic pulmonary fibrosis, the UK has also been identified as an outlier compared with other health systems with similar health related expenditure.4 Deaths from respiratory diseases are amenable to healthcare. The UK has ranked poorly in reports comparing amenable mortality in similar health systems.5 Although measuring outcomes from broad disease categories might have many explanations, this comparative approach remains valuable in assessing overall health system performance. Whether increased respiratory disease mortality in the UK is attributable to smoking, pollution, other environmental factors, or to the delivery of healthcare, requires further evaluation and validation with an independent dataset. Our primary aim was to compare the trends in mortality from respiratory disease in the UK with Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, Australia, Canada, the US, and Norway (also known as the European Union (EU)15+ countries). We performed an observational analysis of the World Health Organization Mortality Database to compare death rates from primary respiratory diseases. We have previously used data from the WHO Mortality Database to assess changes in trends from cardiovascular and cancer mortality,6 and used similar trend analysis to assess UK regional variation in cancer mortality.7 In the current analysis, we have used an independent dataset and longitudinal data to assess trends over a long observation period.Pharmacotherapy for Respiratory Disorders Essay Paper Facts about smoking and respiratory diseases According to the Centers for Disease Control and Prevention (CDC), diseases caused by smoking kill more than 480,000 people in the U.S. each year. In fact, smoking is directly responsible for almost 90% of lung cancer and COPD deaths. Even with antismoking campaigns and health warnings, many people continue to smoke or start to smoke every year. About 8% of kids under age 18 are current tobacco users. What are the risks linked to smoking? Smokers increase their risk of lung disease, including lung cancer. But they also increase their risk of other illnesses such as heart disease, stroke, and mouth (oral) cancer. Risks from smoking, as they relate to lung disease, include the following: Chronic obstructive pulmonary disease (COPD). This includes: Chronic bronchitis. This is a long-term (chronic) inflammation of the large airways (bronchi). Symptoms include coughing mucus over a long period. Emphysema. This chronic lung condition affects the air sacs (alveoli) in the lungs. Symptoms include shortness of breath, coughing, fatigue, sleep and heart problems, weight loss, and depression. Lung cancer. This is an abnormal growth of cells that can result in lumps, masses, or tumors. It may start in the lining of the bronchi, or other areas of the respiratory system. Smoking, including secondhand smoke, is the leading cause of lung cancer. Symptoms of lung cancer include: Cough Chest pain Shortness of breath Wheezing Recurring lung infections Bloody or rust-colored sputum Hoarseness Swelling of the neck and face Pain and weakness in the shoulders, arms, or hands Unexplained fever Other cancers. Smoking increases the risk of lung and oral cancer. But it also increases the risk of other respiratory system cancers. These include cancer of the nose, sinuses, voice box, and throat. Smoking also increases the risk of many other cancers of GI (gastrointestinal), urinary, and female reproductive systems. The symptoms of smoking-related lung diseases may look like other lung conditions or health problems. If you have any symptoms of lung disease, see your healthcare provider as soon as possible.Pharmacotherapy for Respiratory Disorders Essay Paper How dangerous is secondhand smoke? Secondhand smoke is smoke that is exhaled by smokers and smoke emitted from the burning end of a lit cigarette, cigar, or pipe. It causes more than 7,000 lung cancer deaths each year in people who don't smoke. It can also lead to lung conditions and heart disease. Symptoms linked to secondhand smoke exposure may include: Eye, nose, and throat irritation Coughing Too much mucus in the airways Chest discomfort or pain Children and infants exposed to tobacco smoke are more likely to experience ear infections, and asthma. They are also at a higher risk for sudden infant death syndrome (SIDS) than children and infants not exposed to secondhand smoke.   ORDER  NOW   What are the benefits of quitting smoking? People who quit smoking can actually reverse some of the lung damage. Other benefits of quitting smoking may include the following: Decreased risk for lung disease Decreased risk for heart disease Decreased risk for cancer Reduced cigarette stains on fingers and teeth Reduced occurrence of cough Elimination of stale cigarettes smell on clothing and hair Improved smell and taste Saving money by not buying cigarettes How does cigar smoking affect a person's risk of lung cancer and other types of cancer? Cigars actually pose the same, if not greater, risk as cigarettes for oral cancer. Although many cigar smokers do not inhale, their risk for oral, throat, and esophageal cancers is the same as for cigarette smokers. Consider these facts from the CDC:Pharmacotherapy for Respiratory Disorders Essay Paper Compared with nonsmokers, cigar smokers who inhale are more likely to develop oral cancer, esophageal cancer, and laryngeal cancer. Cigar smokers who inhale and smoke 5cigars a day may have a lung cancer risk similar to one-pack-a-day cigarette smokers. Secondhand smoke from cigars contains toxins and cancer-causing agents (carcinogens) similar to secondhand cigarette smoke, but in higher concentrations. How do people stop smoking? Quitting smoking is very difficult. The following tips can help you quit using tobacco products: Think about why you want to quit. Make a list of the reasons. Set a quit date. Try to pick a time when you have as little stress as possible. Ask for support and encouragement from family, friends, and coworkers. If you don't already exercise, start to increase your physical activity to improve your health. Try to get enough sleep each night and eat healthy. Along with exercise, healthy sleeping and eating habits will help you cope with quitting. Join a smoking cessation program or support group. These programs are available in most communities. There are also programs available by phone and online: Try the Smokefree.gov website. Try your state's quitline. Call 800-QUIT-NOW (800-784-8669). Medicines to help you stop smoking There are both prescription and over-the-counter medicines that can help you stop smoking. Talk with your healthcare provider about these medicines and whether or not any of them are right for you. Over-the-counter medicines: Nicotine patch. Nicotine is delivered through the skin. Nicotine gum. Gum delivers nicotine quickly. Nicotine lozenge. Lozenges are like hard candy. Prescription medicines:Pharmacotherapy for Respiratory Disorders Essay Paper Nicotine nasal spray. Nicotine is also delivered quickly. Nicotine inhaler. Using an inhaler is like smoking cigarettes. Antidepressant medicine (bupropion). It helps to lessen cravings for nicotine. Varenicline tartrate. It helps to lessen the discomfort of quitting. It also lessens the pleasure you get from smoking. Long-term effects of air pollution include serious diseases like cancer. The highly polluted city air slowly metamorphoses our healthy and pink colored lung tissues into darkened particles of smog, dust, and other pollutants, making the lungs more vulnerable to infection. The highly sensitive respiratory system can be damaged in a number of ways. Environmental pollution: One of the potent dangers is the environmental pollution. The environment smog contains many chemicals. Many of these chemicals are exhausted by the vehicles and the industries. What is more, several household cleaning products also emit such poisonous gases. Cigarette smoke: This is yet another dangerous emission. The passive smokers are the hardest hit. Burning fags pose a serious threat to our respiratory system. Tobacco smoke contains over 40 chemicals including the dangerous tar. Most of them are known causes of cancer. Approximately 90 per cent of lung cancer cases among men, and more than 70 per cent among women have been traced to smoking. Besides tar several other chemicals enter our lungs from a burning cigarette. The tar from a single cigarette temporarily immobilizes the cilia of the upper and lower tracts of the respiratory route. The tar also temporarily paralyzes the macrophages in the lung alveoli. When the cleansing and filtering functions are made inactive, the lungs and the air passages are laid bare to the different particles, viruses and bacteria that are airborne besides of course the tar. These substances settle down in the lungs' mucous layers. It takes almost an hour for the paralyzed cilia to recover. But repeated paralyzing from the heated tar eventually kills them. Mucus builds up as a result of repeated smoking. The accumulated mucus blocks the smaller air passages. The obstruction triggers the "smoker's cough". This familiar reflex cough is the distressed lung's effort to clear the air routes. Indoor air pollution: This is one of the most dangerous but often disregarded dangers. The offices and homes are mostly bases of indoor air pollution. Many cleaning compounds besides furniture and synthetic carpets, certain construction materials, and even air fresheners emit hazardous gases. These remain highly concentrated in unventilated or AC rooms. The most vulnerable sections of people exposed to these respiratory dangers are children, elderly people and those having a history of respiratory illnesses. These people generally spend most of their time within the four walls. The indoor air pollutants not only weaken our lungs but also invite infections.Pharmacotherapy for Respiratory Disorders Essay Paper Occupational risks: Many professionals are daily exposed to impurities released by their activities. These workers run a high risk of suffering from respiratory diseases. Mention may be made of people picking cotton, those working in work in farms or shipyards, mechanics installing brake insulation or lining. Other people who suffer from such risks are miners, construction workers, quarry workers, stone cutters, and sandblasters among others. Government and NGO Monitoring Of Pollution All the governments have their independent agencies to monitor the pollution levels. There are also non-governmental agencies (NGOs) that carry out this activity. The OSHA (Occupational Safety and Health Administration) in USA, for instance, issues regulations for protection of workers. It has made mandatory the wearing of air masks with filters for certain jobs. The EPA (Environmental Protection Agency) monitors and also regulates the pollutants released into the air by different organizations and industries. In spite of such efforts, across the world, various types of respiratory illnesses have registered a rise. Disorders and Diseases of the Respiratory System Any portion of the respiratory tract can be affected by the disorders and diseases of the respiratory system. Though the common ailments of the respiratory system are trivial, yet at times they can be life threatening as well. Common cold, running nose & stuffy nose: Viruses cause colds by targeting the pharynx and the nasal passages. First, the viruses infiltrate the body through the respiratory system. Then, they target the cells in the nasal passage membranes. But before they can destroy the cells, the body's immune system fights back. The immune system increases the flow of blood to the area. Such reinforcement of white blood cells leads to swelling of the membranes. This causes the stuffy nose. Increase in mucous secretions to neutralize the viral attack leads to the runny nose. Mentionably, the infection can affect the sinuses - membrane-lined cavities located within the head, besides the middle ear and the lower respiratory tract. Hay fever & asthma: These are allergic reactions of the respiratory system. These conditions are caused when the immune system is irritated by irritants like dust or pollen. The symptoms of hay fever are sneezing, watery eyes, and runny nose. It is a seasonal reaction when there is abundance of pollens in the air. Asthma attacks are generally mild. But, they can be life threatening too. A person suffering from asthma experiences difficulty in breathing. It occurs as the bronchi and bronchioles get inflamed and remain constricted temporarily. Laryngitis: Laryngitis is an inflammation of the larynx. Laryngitis is caused by various factors. They can be diverse like voice overuse, cigarette smoke or viral infection. Laryngitis leaves different effects on the voice. Till the inflammation subsides, it can either get hoarse, or get reduced to a whisper. Bronchitis: Bronchitis refers to membrane inflammation. The membranes lining the bronchioles or the bronchi get inflamed. Bronchitis occurs due to bacterial or viral infection. Bronchitis can also happen from irritating chemicals. Pneumonia: This infection of the alveoli is caused by viruses or bacteria. Pneumonia is a potentially serious state of the lungs. In pneumonia the alveoli gets inflamed after fluid builds up. This gathering of fluid and the consequent inflammation impedes the flow of carbon dioxide and oxygen between the alveoli and capillaries. Tuberculosis: Also known as TB, it is caused by the tuberculosis bacterium. The lungs are primarily attacked in TB. At times, other body tissues also get affected. Un-addressed, the lung infection can even destroy the lung tissues. Earlier, tuberculosis was controlled by antibiotics. However, the bacterium has evolved an antibiotic-resistant strain posing a grave health problem. Emphysema: This non-contagious disease affects alveolar tissue gets partially destroyed.Pharmacotherapy for Respiratory Disorders Essay Paper The remaining alveoli gets enlarged and weakened. During exhalation, the bronchioles collapse. As a result, air remains trapped inside the alveoli. In the long run, emphysema affects the patient's ability for exchanging oxygen and carbon dioxide. The circulatory system also fails to function. This causes breathing problems. Emphysema can occur due to genetic factors besides infection, smoke, smog, and cigarette. Lung cancer: The main cancer causing agents are uranium, asbestos, and tobacco smoke. Genetic reasons can also cause cancer. The respiratory cancerous tumors are formed in the lung tissue (alveolar), the bronchioles or the bronchi. Early detection of such tumors can halt their progression to other parts of the body. Then the treatments are more effective, and the prognosis for recovery is rather good. Unfortunately, 85 per cent of the lung cancers are diagnosed at a later stage when the tumors have already spread. In such extreme cases, the prognosis is poor. Respiratory Distress Syndrome: It is also called RDS. The dysfunction refers to a cluster of symptoms. All point to severe malfunctioning of lungs. IRDS: Premature infants may suffer from Infant Respiratory Distress Syndrome (IRDS). IRDS happens when the alveoli fail to fully expand during inhalation. Alveoli expansion needs a chemical called surfactant. However, among the premature infants, the undeveloped alveoli fail to produce enough surfactant. The common treatment for IRDS is administration of air and surfactant through a breathing tube. This administration enables the alveoli to produce surfactant. ARDS: Adult Respiratory Distress Syndrome (ARDS) occurs when the lungs get severely injured. Many automobile accidents, poisonous gases, or lung inflammation can cause such a dysfunction. ARDS patients generally have to battle for life with 50 per cent survival rate. Alternative Treatment for Respiratory Diseases Many traditional and alternative health systems like Yoga, Ayurveda, Unani and Homoeopathy have various means of treating the different types of respiratory disorders. Yoga has simple breathing exercises called 'Pranayam' that have proven track records. The other alternative health systems like Ayurveda, Unani and homoeopathy also have viable strategies to effectively treat the respiratory ailments. However, prior to taking recourse to any of them, one should consult experts of those systems. The purpose of the present study, carried out among a population of confirmed pollution victims living in a designated pollution-affected area, was to determine the association between tobacco use and measures of respiratory function and prevalence of pulmonary symptoms for a period up to 30 years after an improvement in air quality. In particular, we sought to compare these associations in patients with and without diagnosed obstructive ventilatory defects resulting from exposure to air pollution. The present study was embedded in a retrospective cross-sectional analysis of lung function and respiratory symptoms in designated victims of pollution-related illness in Kurashiki between their initial evaluation (from 1976 to 1988) and follow-up in 2009. Study subjects were drawn from the register of pollution victims in Kurashiki. All study participants met the following conditions, as determined by the Public Relief System of Kurashiki City, in accordance with the Pollution-Related Health Damage Special Measures Law (1969) and the Pollution-Related Health Damage Compensation Law (1973): (1) they had resided or were employed within a designated air pollution zone and (2) they were diagnosed with chronic bronchitis, asthma or emphysema by a medical practitioner.Pharmacotherapy for Respiratory Disorders Essay Paper In accordance with the Public Nuisance Countermeasures Law (1967), registered victims were entitled to various forms of compensation including a monthly consultation with a doctor, yearly assessments of respiratory symptoms consisting of a detailed questionnaire and spirometry tests. These patients received treatment with inhaled corticosteroids and long-acting β2 agonists and expectorants, which may have caused improvements in lung function.8 However, this study did not collect detailed data regarding the treatment regimen, and we were therefore unable to evaluate the association between tobacco use and treatment. Of the 419 203 total residents (204 958 male, 214 245 female), 3838 (0.9%) were officially classified as designated pollution victims in the period up to 1988. The records of these 3838 residents were reviewed in 2009 with the permission of the Kurashiki City Public Office (figure 1). Of the 1392 remaining 'officially designated victims of pollution-related illness', we screened 774 individuals aged ≥65 years for inclusion in the study and to focus the study on elderly people. The elderly people have a higher risk factor for the onset of COPD and show remarkably more respiratory symptoms of COPD, as we restricted this study to patients aged over 65 years . After excluding 44 records that did not have complete spirometry data, the resulting sample size was 730 individuals. Ahead of World No Tobacco Day (31 May), the World Health Organization is highlighting the damage tobacco causes to lung health: over 40% of all tobacco-related deaths are from lung diseases like cancer, chronic respiratory diseases and tuberculosis. WHO is calling on countries and partners to increase action to protect people from exposure to tobacco. "Every year, tobacco kills at least 8 million people. Millions more live with lung cancer, tuberculosis, asthma or chronic lung disease caused by tobacco," said WHO Director-General Dr Tedros Adhanom Ghebreyesus. "Healthy lungs are essential to living a healthy life. Today – and everyday – you can protect your lungs and those of your friends and family by saying no to tobacco."Pharmacotherapy for Respiratory Disorders Essay Paper In 2017, tobacco killed 3.3 million users and people exposed to second-hand smoke from lung-related conditions, including: 1.5 million people dying from chronic respiratory diseases 1.2 million deaths from cancer (tracheal, bronchus and lung) 600 000 deaths from respiratory infections and tuberculosis More than 60 000 children aged under 5 die of lower respiratory infections caused by second-hand smoke. Those who live on into adulthood are more likely to develop chronic obstructive pulmonary disease (COPD) later in life. WHO is urging countries to fight the tobacco epidemic through full implementation of the WHO Framework Convention on Tobacco Control (WHO FCTC) and enforcing effective tobacco control actions, including WHO's recommended "MPOWER" policy measures, for example by reducing demand for tobacco through taxation, creating smoke-free places and cessation support. The Organization also encourages parents and community leaders to take steps to safeguard the health of their families and communities by informing them of and protecting them from the harms caused by tobacco. Exposure to tobacco impacts greatly on the lung health of people around the world, including in the following ways: Lung cancer: Tobacco smoking is the primary cause for lung cancer, responsible for over two thirds of lung cancer deaths globally. Second-hand smoke exposure at home or in the workplace also increases risk of lung cancer. Quitting smoking can reduce the risk of lung cancer: after 10 years of quitting smoking, risk of lung cancer falls to about half that of a smoker. Chronic respiratory disease: Tobacco smoking is the leading cause of chronic obstructive pulmonary disease (COPD), a condition where the build-up of pus-filled mucus in the lungs results in a painful cough and agonizing breathing difficulties. The risk of developing COPD is particularly high among individuals who start smoking at a young age, and those exposed to second-hand smoke, as tobacco smoke significantly slows lung development. Tobacco also exacerbates asthma, which restricts activity and contributes to disability. Early smoking cessation is the most effective treatment for slowing the progression of COPD and improving asthma symptoms. Across the life-course: Infants exposed in-utero to tobacco smoke toxins, through maternal smoking or maternal exposure to second-hand smoke, frequently experience reduced lung growth and function. Young children exposed to second-hand smoke are at risk of the onset and exacerbation of asthma, pneumonia and bronchitis, and frequent lower respiratory infections. Smokers should ensure they never smoke in the presence of an infant or young child.Pharmacotherapy for Respiratory Disorders Essay Paper Tuberculosis. Tuberculosis (TB) damages the lungs and reduces lung function, which is further exacerbated by tobacco smoking. About one quarter of the world's population has latent TB, placing them at risk of developing the active disease. People who smoke are twice as likely to fall ill with TB. Active TB, compounded by the damaging lung health effects of tobacco smoking, substantially increases risk of disability and death from respiratory failure. TB sufferers should take immediate steps to quit tobacco to enable their TB treatment regime to be effective. Air pollution: Tobacco smoke is a dangerous form of indoor air pollution: it contains more than 7 000 chemicals, 69 of which are known to cause cancer. Though smoke may be invisible and odourless, it can linger in the air for up to five hours. How tobacco relates to the SDGs: In order to achieve the Sustainable Development Goal (SDG) target of a one-third reduction in NCD premature mortality by 2030, tobacco control must be a priority for governments and communities worldwide. The world is not on track to meet this target. Subscribe to the WHO newsletter → Media Contacts Paul Garwood More recent work in transgenic mice has found that overexpression of epithelial sodium ion channels resulted in excess reabsorption of epithelial sodium and volume depletion of periciliary fluid (Mall et al. 2004). The depletion of the periciliary fluid layer interferes with the frequency of ciliary beats and results in decreased clearance and adherence of mucus to the airway surface. Results of this study showed that depletion of the periciliary fluid in animals is associated with the accumulation of mucus in the lumen of both large and small airways, leading to greater susceptibility to infection of the lower respiratory tract and early death.Pharmacotherapy for Respiratory Disorders Essay Paper Chronic Obstructive Pulmonary Disease The hallmark of COPD is chronic airflow obstruction demonstrated with spirometry and the accompanying dyspnea and limitation of activity. Maximum expiratory flow is determined by the product of the resistance to flow in the small conducting airways (centimeters of water [H 2O] per liter per second) and the elastic recoil of the lung parenchyma that drives expiratory flow (liters per centimeter of H2O). The product of these two variables, the time constant, characterizes the rapidity with which the lung fills and empties during respiration. Surprisingly, the time constant of the lung remains stable over a wide range of breathing frequencies in healthy lungs, but if disease increases either the compliance as in emphysema or the resistance as in obstruction of small airways, the time required to empty the lung is prolonged (Otis et al. 1956). The presence of a fixed limitation in airflow can be diagnosed by using a spirometer to measure the volume of air that can be forcibly expired from the lungs in one second (forced expiratory volume [FEV1]) and then determining its ratio to forced vital capacity (FEV1/FVC) after the administration of a bronchodilator. The classic cohort study of the natural history of chronic bronchitis and emphysema performed by Fletcher and colleagues (Lancet 1965; Fletcher 1976) used this type of measurement to test the hypothesis of a sequence beginning with tobacco smoking and then moving to symptoms of chronic bronchitis or recurrent chest infections and, finally, chronic limitation of airflow. The natural history of the decline in FEV developed by Fletcher and colleagues (1976) to summarize findings of a six-year longitudinal study of men working in West London is illustrated in Figure 7.4. Subsequent studies have confirmed these findings (USDHHS 1984). The horizontal lines added to the Fletcher diagram indicate the boundaries of the five-stage classification of the severity of COPD by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The measurements used were FEV1 and FEV1/ FVC (Pauwels et al. 2001; GOLD 2006). According to this classification, GOLD stage 0 defines persons with a normal FEV1 and FEV1/FVC who have symptoms attributable to significant exposure to tobacco smoke as being at risk for developing COPD. Those with mild, moderate, severe, or very severe COPD are placed in GOLD stages 1 through 4, respectively (Takeyama 2001b). Natural history of decline in forced expiratory volume with aging measured in a group of working men in West London over about six years. Source: Hogg 2004. Reprinted with permission from Elsevier, © 2004. Note: Adapted from Fletcher et al. 1976. (more...) Fletcher and colleagues (1976) observed that only 15 to 25 percent of the smokers in the study developed air-flow limitation, and they showed that smoking cessation slowed the rate of decline in FEV1 in those who stopped smoking permanently. In subsequent studies of various populations, only a minority of smokers developed COPD. This repeated finding indicates a role for genetic factors that may determine susceptibility to cigarette smoke. These investigators rejected the hypothesis of a pathogenetic continuum from smoking to obstructive bronchitis. Most persons who developed airflow limitation during the study had no evidence of chronic bronchitis, a finding that was not consistent with the hypothesis of a continuum from smoking to bronchitis to obstruction. Subsequent studies have confirmed that the presence of chronic bronchitis in persons with normal lung function (GOLD stage 0) does not predict progression of disease (Vestbo and Lange 2002). Using data from the Copenhagen City Heart Study, however, Vestbo and colleagues (1996) found that the symptoms of chronic bronchitis were associated with an accelerated decline in FEV1. Acute exacerbations, a concern in treatment of COPD, are attributed to viral infections (Monto et al. 1975; Smith et al. 1980; Seemungal et al. 2001), bacterial infections, and occupational and environmental air pollution; an important residual of cases had no obvious cause (Pauwels et al. 2001; Rabe et al. 2007). Some unexplained exacerbations of COPD might be attributable to latent viral infection, because such infections can deregulate the expression of adhesion proteins that might initiate this response (Gonzáles et al. 1996; Keicho et al. 1997). Although Fletcher and colleagues (1976) found that these exacerbations had no effect on the rate of decline of FEV1 in the working men in West London, the U.S. Lung Health Study showed that such exacerbations were associated with a more rapid decline in persons with mild disease who continued to smoke (Kanner et al. 2001). Subsequently, other investigators found that frequent exacerbations in patients with more severe COPD, especially those resulting from a higher bacterial load, were associated with more accelerated decline in FEV1 (Donaldson et al. 2002; Wilkinson et al. 2003). Collectively, these data suggest that when lung defenses become compromised in the later stages of COPD, chronic infection might play a role in the pathogenesis of the airflow limitation.Pharmacotherapy for Respiratory Disorders Essay Paper Obstruction of Small Airways Although spirometric measurement of FEV1 and the FEV1/FVC provides a reliable method for diagnosing airflow limitation and classifying its severity, spirometry cannot distinguish the contributions of either the obstruction of small airways or emphysematous destruction to the airflow limitation in COPD. Direct measurements of pressures and flows within the lung have shown that the small bronchi and bronchioles (<2 mm in diameter) are the major sites of airway obstruction in COPD (Hogg et al. 1968; van Brabandt et al. 1983; Yanai et al. 1992). This obstruction is related to an inflammatory process that thickens the airway wall, fills the lumen with exudates containing mucus, and narrows the airway by depositing connective tissue in the airway wall (Figure 7.5). McLean (1956) and Leopold and Gough (1957) recognized that an inflammatory process was present in the small bronchi and bronchioles of lungs affected by centrilobular emphysema. Leopold and Gough (1957) hypothesized that centrilobular emphysema resulted from an extension of this process from the small conducting airways into the respiratory bronchioles. Later, Matsuba and Thurlbeck (1972) demonstrated an excess deposition of connective tissue in the adventitia of the small conducting airways in advanced emphysema and suggested that peribronchiolar fibrosis narrowed the airway lumen. In addition, cross-sectional studies of the pathology of COPD have shown that the peripheral inflammatory immune process found in the lungs of all smokers is amplified in severe (GOLD stage 3) and very severe (GOLD stage 4) COPD (Fletcher et al. 1976; Hogg et al. 2004). More recent evidence indicates that at these levels of disease severity, these changes are associated with an increase in the adaptive immune response. These findings may reflect the response to an antigenic stimulus from a limited number of antigens that might be microbial or possibly from autoantigens that develop within the damaged lung tissue (Agustí et al. 2003; Voelkel and Taraseviciene-Stewart 2005). Nature of an obstruction in the small conducting airways (<2 millimeters in diameter). Source: Hogg 2004. Reprinted with permission from Elsevier, © 2004. Note: A normal airway (A) is compared with another airway (B) in which the lumen (more...) Emphysema Emphysema was first described by René Laënnec in 1834 on the basis of observations made on the cut surface of postmortem human lungs that had been air-dried in inflation (Laënnec 1834), but the concept that emphysematous destruction produced airflow limitation by decreasing the elastic recoil forces required to drive air out of the lung was not fully developed until 1967 (Mead et al. 1967). The earliest concept regarding the pathogenesis of emphysema postulated that overinflation compressed the lung capillaries, leading to atrophy of lung tissue; this concept was mentioned in major textbooks of pathology as late as 1940 (McCallum 1940). As mentioned previously (see "Obstruction of Small Airways" earlier in this chapter), McLean (1956) and Leopold and Gough (1957) were the first to implicate the inflammatory response in the pathogenesis of alveolar destruction in their early descriptions of centrilobular emphysema, but skepticism about this association persisted because of the possibility that preterminal bronchopneumonia may have been responsible for the inflammation observed in the postmortem studies. The subsequent demonstration that emphysema could be produced experimentally by depositing the enzyme papain in the lung (Gross et al. 1964), combined with observational studies showing the association between emphysema and deficiency of α1-antitrypsin (AAT) (Laurell and Eriksson 1963), led naturally to the hypothesis that the pathogenesis of emphysema was based on a functional proteolytic imbalance within the inflammatory response induced by tobacco smoke(Gadek et al. 1979). Currently, emphysema is defined as "abnormal, permanent enlargement of air spaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis" (Snider et al. 1985, p. 183). The condition can now be diagnosed and quantified during life by several techniques. Postmortem examinations have provided indirect information on the prevalence of emphysema (Thurlbeck 1963; Ryder et al. 1971).Pharmacotherapy for Respiratory Disorders Essay Paper An important study from the United Kingdom (Ryder et al. 1971) found emphysema in 62 percent (219) of 353 consecutive postmortem examinations. On average, when present, the condition occupied 12.6 percent (range, 0.5 to 95 percent) of total lung volume. Smoking history was established in 179 of the 353 patients, and emphysema was present in 75 percent (80) of the 106 smokers. The mean proportion of total lung volume occupied by emphysema in smokers was 10.8 percent (range, 0 to 90 percent). Emphysema was also present in 28 percent (21) of 73 nonsmokers, but the mean proportion of the lung taken up by emphysema in nonsmokers was only 1.7 percent (range, 0 to 40 percent). In addition, the nonsmokers lived longer than the smokers (aged 64.8 versus 60.2 years; p <0.05) and emphysema appeared at a later age (Ryder et al. 1971). A laboratory study of more than 400 lungs removed from patients being treated for lung cancer (Hogg 2004) confirmed that a small proportion of smokers had emphysema and that the proportion with emphysema increases with the number of pack-years of smoking. However, the dose-response relationship plateaus at 50 to 100 pack-years, and about 40 percent of smokers are affected (Figure 7.6). Although imaging by computed tomography (CT) has now confirmed that emphysema can be found in persons with a normal FEV1, population-based studies of its prevalence, as detected by CT, have not been attempted. Dose-response relationship between level of smoking and the percentage of 408 patients in the St. Paul's Lung Study with morphologic evidence of significant emphysema in their lungsa. Source: Hogg 2004. Reprinted with permission from Elsevier, (more...) Centrilobular and Panacinar Forms of Emphysema Pathologically, emphysema is characterized by its location as centrilobular or panlobular; the radiographic correlates are centriacinar emphysema and panacinar emphysema, respectively (Friedlander et al. 2007). Centrilobular emphysema is characteristic of smokers, whereas panacinar emphysema is found with AAT deficiency. In general, persons with a predominance of centrilobular emphysema have physiological abnormalities consistent with abnormal function of small airways, whereas panlobular emphysema is associated with high lung compliance. A substantial portion of people with emphysema have both types. A postmortem bronchogram from a patient with lesions of centrilobular emphysema visible at a microscopic low power is shown in Figure 7.7. The nature of these lesions is shown to better advantage in Figure 7.8. Several normal terminal bronchioles within a secondary lung lobule (A) and the histology of a normal acinus beyond a single terminal bronchiole (B) can be compared with a line drawing from Leopold and Gough's (1957) original description of centrilobular emphysema (C) and a postmortem radiograph showing the destruction of the respiratory bronchioles (D). These centrilobular lesions affect the upper regions of the lung more commonly than the lower regions (Figure 7.9) and are also larger and more numerous in the upper lung (Gadek et al. 1979). Heppleston and Leopold (1961) used the term "focal emphysema" to describe a less severe form of centrilobular emphysema, but Dunnill (1982) argued that this distinction was not helpful and that the two conditions probably had a similar origin, with focal emphysema being more widely distributed and less severe than the classic centrilobular form. Dunnill also preferred the term "centriacinar" to "centrilobular." "Centriacinar" seems more suitable in that each secondary lobule contains several acini (Figure 7.8A) and not all are involved in emphysematous destruction.Pharmacotherapy for Respiratory Disorders Essay Paper Respiratory agents is a term used to describe a wide variety of medicines used to relieve, treat, or prevent respiratory diseases such as asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), or pneumonia. Respiratory agents are available in many different forms, such as oral tablets, oral liquids, injections or inhalations. Inhalations deliver the required medicine or medicines directly to the lungs, which means the medicine(s) can act directly on the lung tissues, minimizing systemic side effects. Some products contain more than one medicine (for example, inhalers that combine a long-acting bronchodilator with a glucocorticoid). Many respiratory drugs are given by inhalation, although enteral, parenteral, transdermal, or topical routes of administration may be used for some agents. Giving medications by the inhaled route has several advantages over systemic administration: a smaller dose can be used, adverse effects are often reduced, the drug is delivered quickly to lung tissue or the bloodstream, administration is painless, and delivery is usually safe and convenient.1 Bronchodilators These are the most frequently used inhaled medications. Bronchodilators can be subdivided into sympathomimetic (adrenergic) drugs and parasympatholytic (anticholinergic) drugs, as well as being classified as short acting or long acting. The adrenergic drugs stimulate the sympathetic nervous system, while anticholinergic drugs block the parasympathetic system. Adrenergic agents work to cause bronchodilation; anticholinergic drugs block bronchoconstriction. Short-acting drugs are effective for 4 to 6 hours and long-acting bronchodilators generally last about 12 hours. Albuterol is a commonly used bronchodilator and is a short-acting ß2-adrenergic agonist (SABA). Salmeterol is delivered in a dry-powder inhaler (DPI) and is a long-acting ß2-adrenergic agonist (LABA). Levalbuterol is the R enantiomer of racemic albuterol and is a frequently used inhaled drug for bronchodilation. This is a single-isomer drug (the other isomer has been removed). More single-isomer medications are being developed and released for use because these drugs tend to reduce adverse effects such as tremors and tachycardia.Pharmacotherapy for Respiratory Disorders Essay Paper Recently, formoterol was added to the list of adrenergic agents; it is a LABA. Formoterol is administered using a DPI. In October 2006, the US Food and Drug Administration approved the R-R enantiomer of formoterol for marketing as arformoterol. This drug is a single-isomer formulation indicated for use in chronic obstructive pulmonary disease (COPD). Arformoterol is not indicated for acute problems and is not approved for use in pediatric patients. It is administered twice daily and supplied as a 2-mL unit dose for nebulization. Each dose contains 15 µg of arformoterol with isotonic saline as the diluent. It should not be used in conjunction with any other LABA. The SABA medications are used to provide short-term relief from the bronchospasm and shortness of breath most often associated with asthma and COPD. The LABA medications are for longer-lasting relief and are also useful in treating asthma and COPD. Rau1 lists 12 inhaled adrenergic bronchodilators. In the current practice of respiratory care, however, four or five of these are commonly administered. Anticholinergic medications provide relief from bronchospasm and shortness of breath. They can be used alone or in combination with SABA and LABA. They are frequently prescribed for patients with asthma or COPD. Of the anticholinergic drugs, respiratory therapists are probably most familiar with ipratropium. Ipratropium works at the muscarinic receptors and blocks transmission of the parasympathetic response. The combination of albuterol and ipratropium has a significantly better effect than one or the other alone.1A newer formulation of this type of bronchodilator is tiotropium, which targets more specific muscarinic receptors. Tiotropium has a longer pharmacological half-life and promotes bronchodilation for 24 hours.2 Many patients with congestive heart failure, coronary-artery disease, or hypertension take medications that block the ß1-receptors. These ß-blockers could also be termed sympatholytics. Upon the initial release of these drugs in the 1960s, physicians were advised to avoid using them to treat patients with COPD or asthma (due to the possibility of bronchospasm). As the ß-blocking drugs have become more specific to cardiac receptors, however, this potential problem has been eliminated, and the use of cardioselective ß-blockers has become common in patients who also have COPD or asthma.3,4 Corticosteroids Corticosteroids are anti-inflammatory glucocorticoids used primarily for patients with asthma, but they are of some use in COPD as well (particularly for patients with severe COPD and frequent exacerbations). Corticosteroids inhibit many of the cells involved in the inflammatory response (such as eosinophils, T-lymphocytes, mast cells, and dendritic cells5) and help to increase the diameter of the airways by reducing swelling. By inhaling these medications, patients minimize many of their systemic adverse effects, which can include suppression of the hypothalamus, pituitary, and adrenal glands; osteoporosis; mood changes; fluid retention; hypertension; an increased white–blood-cell count and a shift in the normal differential; cushingoid appearance; and growth restriction. Nonetheless, some adverse effects are associated with inhaled steroids. These include oral candidiasis, hoarseness and changes in the voice, and cough. These problems can be minimized through the use of a spacer with a metered-dose inhaler (MDI), along with brushing the teeth and gargling to help reduce residual medication in the oropharynx after using the inhaled medication. Recently developed inhaled steroids provide long-lasting drug coverage that does not require the patient to take multiple puffs from an inhaler, helping to increase compliance. Fluticasone, budesonide, and (most recently) mometasone have become popular as effective steroids that reduce the number of puffs needed; mometasone, for example, can be effective for some patients who use just a single puff of 220 µg in the evening. Some inhaled steroids developed earlier required as many as four to 10 puffs at a time to manage symptoms. Budesonide has an advantage over other steroids in that it can be nebulized; every other steroid used in the United States is available only as a DPI or MDI.Pharmacotherapy for Respiratory Disorders Essay Paper Mast Cell Stabilizers and Anti-IgE Antibodies Nedocromil and cromolyn sodium are older, well-known drugs. Both work to stabilize mast cells and prohibit release of asthma-related chemical mediators such as histamine, leukotrienes, and cytokines from the mast cell. Both drugs are included in the 2002 National Asthma Education and Prevention Program (NAEPP) guidelines6 and the 2006 Global Initiative for Asthma (GINA) guidelines.7 The third drug in this category is omalizumab, which is injected subcutaneously every 2 to 4 weeks to treat patients with refractory, severe asthma. These three drugs are not used to treat COPD, since problems with mast cells do not appear to be part of its clinical picture. Omalizumab stops immunoglobulin E (IgE) from binding to mast cells and basophils, thus preventing the release of chemical mediators. Patients must be more than 12 years old to use this drug, and administration must be closely monitored for the first 2 hours after injection due to serious side effects, including anaphylaxis, the severe (and sometimes fatal) systemic reaction to an allergen.8 Patients who might be candidates for treatment with omalizumab must have their total serum IgE levels tested and their current body weight measured for the correct dose to be determined. IgE levels do not need to be monitored after treatment starts; these levels actually increase during treatment, but they hardly influence inflammation because they are countered by the effects of omalizumab. Three groups of patients are considered to benefit most from using this medicine: those who are using high doses of inhaled steroids and are sensitive to perennial allergens such as dust mites, cockroaches, and pet dander; those who have frequent exacerbations; and those who comply poorly with their medication regimens and may have severe symptoms.9 According to the GINA guidelines, the use of omalizumab should be considered for patients who have severe, uncontrolled asthma despite the regular use of inhaled steroids. Omalizumab should be considered an add-on medication; the other drugs being used should be continued as indicated by asthma severity.10 Leukotriene Receptor Antagonists Asthma patients use these medications to block the effects of leukotrienes as part of the inflammatory cascade. There are three drugs on the market that work in this area: zafirlukast, montelukast, and zileuton. Of the three, montelukast may be preferred. It is the only drug approved for children 2 or more years old (zafirlukast is approved for those older than 6; zileuton, for those 12 and older). In addition, zileuton has an adverse effect involving liver toxicity, and the manufacturer recommends monitoring liver enzymes when it is used. These three agents are taken orally and are not used in treating respiratory disorders other than allergic responses and asthma. Antihistamines and Epinephrine There are numerous first-generation antihistamines such as diphenhydramine and chlorpheniramine on the market, and most are available over the counter. There are three notable second-generation drugs: loratadine, fexofenadine, and cetirizine. These are longer lasting and less sedating than the first-generation drugs, so they are frequently used to treat allergies and asthma. All of them are supplied in pill form. Anaphylaxis is treated using epinephrine, usually given intramuscularly or subcutaneously. Some patients with severe allergies carry a single-use injection of epinephrine for use in an allergic emergency.Pharmacotherapy for Respiratory Disorders Essay Paper Respiratory Stimulants Drugs in this category include doxapram, progesterone, caffeine, and theophylline. Doxapram has been used primarily to help preterm infants who have apnea, but has also been somewhat helpful in older patients with sleep apnea and in COPD patients with acute respiratory failure. Likewise, progesterone, caffeine, and theophylline have been cited in the literature11,12as having limited roles in stimulating the respiratory system. Although these medications bring about short-term apnea relief and increase ventilation, there are only limited data to support their routine use. Pulmonary Surfactants Treatment for neonates with immature pulmonary systems has included exogenous surfactant for many years. In 1990, colfosceril was approved for use, and it was followed by beractant in 1991. In 1998, calfactant was approved, followed by poractant alfa. Colfosceril is the only surfactant that is classified as synthetic; all the others are natural, with their ingredients taken from animals or humans through alveolar lavage or using amniotic fluid. All of the surfactant preparations are given via endotracheal-tube instillation, with varying dosage, handling, and instillation details. Surfactant therapy has been studied in patients with acute lung injury (ALI) and/or adult respiratory distress syndrome (ARDS), with mixed results. Currently, there are two notable trials looking further into the use of exogenous surfactant in ALI/ARDS. One study is focusing on patients who had either aspiration or pneumonia as the underlying cause of ALI/ARDS, since part of the benefit of surfactant is its anti-inflammatory and antibacterial functions. Progression from direct lung injury to ALI/ARDS may be blunted or stopped by early initiation and longer duration of surfactant therapy. The second study is looking at using surfactant lavage via bronchoscopy, reaching lung segments to clear damaging proteins.13 Antimicrobials and Antivirals Inhaled agents that fight infection include the antimicrobials pentamidine and tobramycin and the antivirals ribavirin and zanamivir. Pentamidine is used to prevent Pneumocystis carinii pneumonia in patients with AIDS. Tobramycin is used to treat Pseudomonas aeruginosa infections, mainly in patients with cystic fibrosis; it has also been used to fight P. aeruginosa in lung-transplant recipients. Ribavirin is used to treat severe infections caused by respiratory syncytial virus. Zanamivir is an antiviral agent used to treat influenza in adults. It has recently gained attention as the inhaled drug of choice to fight possible pandemic influenza.Pharmacotherapy for Respiratory Disorders Essay Paper Guaifenesin is a commonly used over-the-counter expectorant that is now being advertised heavily. This re-emphasis is curious, however, since the American College of Chest Physicians' evidence-based clinical practice guidelines14 on therapy to decrease cough frequency and/or intensity stated that guaifenesin was ineffective in enhancing cough clearance in patients with chronic bronchitis. The drug was not mentioned in any of the 15 ACCP recommendations on cough suppressants and pharmacological protussive therapy. Varenicline is a medication for smoking cessation that it thought to bind to the nicotine receptors in the brain. When the nicotine receptors are tied up by varenicline, the pleasurable sensation associated with smoking is blunted. Beyond this desired effect, varenicline has several adverse effects that reinforce the desire to quit smoking, including nausea, headache, and sleeping/dreaming abnormalities. In respiratory therapy, a few medications are considered drugs of choice. As resources for physicians and other prescribing clinicians, however, therapists should always be aware of new medications coming up through research channels. Likewise, they should be among the first to know about newly released pulmonary medications (including their indications, dosages, routes of administration, adverse effects, contraindications, and expected outcomes). Therapists should be participating in research to verify the effectiveness of new drugs, and they should provide drug education for patients, families, and the other members of the health care team. Pharmacotherapy for Respiratory Disorders Essay Paper