New Drugs for Asthma - Coursework Example

NEW DRUGS FOR ASTHMA by Student’s Name Code + Course Name Professor’s Name University Name City, State Date New drugs for asthma Introduction Asthma is regarded as one of the most prevalent inflammatory infections in the world today, with most cases responding well to available treatments which are mostly inhaled corticosteroids. According to Weiss and Sullivan (2001, P.6), initial approaches to the treatment of this infection emphasized on the use of β2-adrenergic agonists with the aim of relieving bronchoconstriction but with time, medical experts discovered airway inflammation that informed the use of corticosteroids as the major treatment therapy for asthma. Despite the success rate, 5-10 % of the patients suffer a chronic form of this disease that responds poorly to the available treatment (Leath, Singla, and Peters, 2005, p.1650). This has led to a lot of research into new and novel therapies that will help in managing this chronic inflammatory infection. The establishment of new drugs to treat asthma has been dependent on the improvement of the existing drugs or the development of totally new approaches and whatever the approach, the following are possible treatments for asthma. Classification of New Possible Strategies  New Corticosteroids Nearly all the corticosteroids used to treat asthma are inhaled, which implies that they are absorbed directly from the lungs into the systemic circulatory system. Barnes (2009, p.297) points out that this mode of administration carries greater odds for systemic side effects when the corticosteroids are used in high dosages. For quite some time, the medical industry has tried various strategies to mitigate the systemic side effects, including the administration of inactive prodrugs as well as the use of dissociated corticosteroids as argued by Adcock, Caramori, andChung, (2008, p.1077).Barnes (2009, p.299) identifies two variations of corticosteroids that have emerged in an attempt to move closer to more effective asthma therapies: 1. Dissociated corticosteroids DNA binding has been identified as a major strategy that could be used to inhibit the outcomes of pro-inflammatory transcription factors. These novel corticosteroids that are otherwise referred to as dissociated corticosteroids are meant to trans-repress most of pro-inflammatory genes and they include RU40066 and RU24858. These are all under clinical development and have so far indicated positive results with regard to the treatment of asthma (Barnes, 2009, p.297). 2. Soft steroids As defined by Barnes (2009), these are corticosteroids that have been deactivated with the help of esterases in the user’s airways. Ideally, any traces of corticosteroids that are coincidentally not blown to the airways will not be available for absorption. In most of the clinical studies that involved tipredane and butixocort soft steroids, these two were ineffective in the treatment of the inflammatory infection, perhaps because they were inactivated prior to their arrival in the target cells. In similar testing approaches, however, Ciclesonide that is a soft steroid, depicted desirable anti-inflammatory effects and could therefore be the next big thing in the treatment of asthma (Weiss and Sullivan, 2001, p.8). New Bronchodilators Β2-adrenoceptor antagonists have been so far the most effective bronchodilators in the treatment of asthma despite the fact that clinicians have conducted multiple studies to come up with novel bronchodilators. New Drugs under Development According to Barnes (2009, p.298), nearly all the new categories of bronchodilators developed have relied on the knowledge obtained from the action mechanisms of β2-adrenoceptor agonists. Some of the new bronchodilators developed this far include: Vasoactive Intestinal Peptides This compound is used as a relaxant for constricted human airwaves but it has been shown to degrade along the airway epithelium, a reason why it has not been highly effective in treating asthma according to Barnes and Dixon (2004,p. 164). Even so, clinical trials have resulted in a more proactive strain of this compound, which has a prolonged effect and is thought to be highly effective on asthmatic patients. Atrial Neurotic Peptide In Lipworth’s definition, (2009, p.941), this is a form of therapy that is administered through intravenous injections, eliciting one of the strongest bronchodilator effects. Besides protecting the user from the bronchoconstriction that is normally a consequent of inhaled bronchoconstrictors, it has a longer action duration and besides, some forms of this compound are less susceptible to degradation that could otherwise water down its effectiveness. Interleukin Inhibitors Morishita, Tomita, and Ohigara (2004, p.140), argue that Interleuking-5 has been identified as one of the substances that orchestrate a certain inflammation of asthma and unless an inhibitor is developed against such a substance, it becomes a little difficult to treat the inflammation with the help of common drugs. Most of the interleukin inhibitors that have been developed to fight against asthma have been tested in mice and the response is quite positive with regard to the suppression of interleukin-5. Similarly, some antibodies that serve as interleukin inhibitors have been developed, with one of them being humanized monoclonal antibody, which is aimed at suppressingeosinophils that causes asthma (Morishita, Tomita, and Ohigara, 2004, p.140). Studies have indicated that just one intravenous injection of this antibody will significantly lower the level of eosinophils in blood for a duration of approximately three months. Over this period, there will be no eosinophilpenetration into the airwaves and as a result, patients with mild forms of asthma will not suffer problematic responses to allergens (HOUSLAY and ADAMS, 2003, p. 13). Cytokines Cytokines have been in existence for quite some time but one of the reasons why they are not medically feasible is the fact that they are not cost-effective in instances where they ought to be used as a form of long-term therapy. Even so, research has indicated that in a few days, it is possible to develop drugs that will ultimately release endogenous cytokines or where necessary, activate their signal transduction pathways. One of these cytokines is IL-10, which prevents the synthesis of the inflammatory proteins which are mostly over-expressed in asthmatic patients (Lipworth, 2009, p. 941). Chemokine receptor inhibitors There are averagely 50 chemokines that are thought to welcome inflammatory cells through the activation, of several surface receptors (Rossi and Zlotnik, 2000, p.222). As most studies have indicated, chemokine receptors are majorly G-protein receptors, which renders them acquiescent of small-molecule receptors. In most of the instances where these inhibitors have been used, it is not yet clear whether the strategy is feasible (Schleimer and Bochner, 2008, p.19). In another approach, however, clinicians have preferred the use of antibodies as inhibitors, which result into a long blockade duration. Some of these chemokine inhibitors are highly selective especially with small chemokines but will be so effective in mediating the major effects of some chemokines (Rossi and Zlotnik, 2000, p.229). Gene therapy It is popular knowledge that atopic diseases depict a polygenic nature, which makes it unlikely for gene therapy to work for infections such as asthma. Contrary to this fact, however, a basic understanding of gene therapy is required in the long term especially in developing a lasting solution to some of these illnesses(Stenton et al., 2002, p.1034). With regard to asthma, understanding gene therapy will be helpful in understanding the severity of this disease and will act as a baseline in develop molecular targets towards the establishment of novel drug solutions (Nice and Metzger, 2007, p.723) One of the antisense solutions that have been developed to mitigate the disease is antisense oligonucleotide, which is an inhaled compound. It has been targeted at the adenosine A1 receptor and it indicated a reduced case of asthma in rabbits (Nice and Metzger, 2007, p. 726). It is a significant step in testing the possibility of using this route to treat and control asthma and further clinical trials have attested to the fact that this form of therapy is feasible. Anti-allergy drugs Anti-allergy drugs will perhaps be more effective compared to most of the novel categories that are targeted towards the suppression of asthma because they are more likely to selectively counter the atopic disease process. The use of co-stimulation inhibitors has been brought forth as one of the major anti-allergy strategies that will be used to treat asthma (Djukanovic, 2000, p.48). Co-stimulation inhibitors are highly effective in augmenting the contact between DC4+ cells and antigen-presenting cells. Inducible co-stimulatory molecule (ICOS) has shown a good deal of significant results when fought against using anti-allergy drugs because of its ability to bind with B7-like molecules. (Djukanovic, 2000, p.50).Blocking the ICOS molecule directly inhibits TH2 cells from developing and prevents the allergic reactions that are likely to arise in the process. Cell-adhesion blockers The ability of inflammatory cells to infiltrate into tissues will depend on the adhesive ability of blood-borne inflammatory cells, especially to endothelial cells because a lot happens before the inflammatory cells finally migrate to take their position in the inflammatory site (Vieira et al., 2004, p.1287). To prevent the process of cell adhesion, it will take the use of monoclonal antibodies that are known to prevent the adhesion of molecules. Using such monoclonal antibodies as (ICAM1) on the fundamental endothelial cells, will block the eosinophils from infiltrating into the airwaves and as a result, it will be a highly effective asthma therapy. The antibodies have already been used in sensitized primates and they have proved effective in preventing an increase in bronchial activity (Vieira et al., 2004, p.1287). Kinase inhibitors The kinase pathway of the p38 mitogen-activated pathogen has been of particular interest to clinicians and researchers who are out to develop noel treatment strategies to asthma (Kumar, Boehm, and Lee, 2003, p.719). Their approach has been highly welcomes in the medical industry since this kinase pathway has been involved in the expression of multiple inflammatory proteins that are particularly linked to asthma (Wegner et al., 2000, p558). Kinase inhibitors work by simply preventing the synthesis of inflammatory cytokines, enzymes and chemokines. These kinase inhibitors also work by activating apoptotic pathways, thereby preventing the survival of eosinophils (Wegner et al., 2000, p558). One such inhibitor is aerosolized Syk antisense oligodeoxynucleotide, which has been tested in mice and results indicate that it can prevent allergen-induced inflammations Phosphodiesterase-4 inhibitors Phosphodiesterases have a long record of synthesizing cyclic nucleotides that could otherwise slow down the process of cell activation. Theophylline for instance, has a longstanding history of use as an asthma treatment therapy but it has been criticized as a non-selective and overly weak PDE-inhibitor (Essayan, 2001, p.680) PDE4 is perhaps the breakthrough in this category, which is also a principal member of the PDE family. With regard to the suppression of inflammatory cells, PDE4 inhibitors are highly effective because they have been used by atopic patients (Essayan, 2001, p.677). PDE4 inhibitors have been used in animal models and the results indicate that it prevents the infiltration of eosinophils. Conclusion It is common knowledge that asthma continues to be a prevalent atopic infection in the world today. In response to this, researchers and clinicians are constantly at work to try and develop more effective drugs that would replace corticosteroids and bronchodilators. While some of these asthma therapies are highly effective, they carry the potential of systemic side effects, a reason why new options such as PDE4 inhibitors, cell adhesion blockers and gene therapy are emerging as possible treatments to replace the initial options. Reference List Adcock, I. 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