Exploration of Pharmacology Case for Asthma- myassignmenthelp

Question: Discuss about theExploration of Pharmacology Case for Childhood Asthma. Answer: Introduction: Asthma is a chronic inflammatory and allergic disease associated with symptoms like insufficient breathing, coughing and wheezing. Childhood asthma is more prevalent and nocturnal cough is the most prominent symptom of it. Patient in this case, Jessica is having asthma. She is five-year child and she is showing symptoms like cold, nasal discharge, nocturnal cough and breath shortness. Risk factors responsible for the occurrence of asthma are cold air, exercise, pollen and viruses. It can also occur due to medications like aspirin and blockers. Genetic factors also play major role in the occurrence of asthma. Type 1 hypersensitivity reactions occur in asthma. In this paper different aspects of asthma in Jessica are discussed. These aspects include pathophysiology, treatment and symptoms related to the asthma. Pharmacology: Constriction is a prominent feature of asthma. Constrictions of the airway can lead to the constriction of muscle surrounding chest which results in the tightness of the chest. Breathing problem in the asthma patients results in the lowered oxygen saturation in asthma patients which results in the diminished supply of oxygen to muscles and cells. Deficiency of oxygen can lead to development of fatigue in asthma patients. Patients with progressive and worsening asthma exhibit nocturnal asthma which results in insomnia and fatigue in the daytime (Krishnan et al., 2012; S124-35). Bronchoconstriction produces shortness of breath in Jessica. Hence, bronchodilator such as salbutamol was being administered to her. Salbutamol in the form of inhalation is useful as bronchodilator in asthma patients. Inhaled salbutamol exhibits peak plasma concentration at 3 4 hours after inhalation. Hence, Jessica can get relieved from the breathlessness after 3 4 hours after its administration. Inhaled salbutamol exhibits average plasma half-life of 4 6 hours. However, literature indicate that salbutamol can exhibit bronchodilation within five minutes of its administration, irrespective of the plasma concentration. Hence, inhaled salbutamol can exhibit its efficacy upto approximately 20 hours because concentration of drug become approximately negligible after 4 half-lives. Salbutamol metabolism occurs through phase II metabolism and it produces glucuronide and sulphated conjugates. Approximately 85 % of the inhaled drug can be detected in the urine after 48 hours. It indicates that there is not complete elimination of drug in Jessica after 48 hours. Hence, there can be bronchodilation and improvement in breathing in Jessica within five minutes of its administration and it can lasts upto 4 6 hours. Inflammation is the main mechanism responsible for the occurrence of asthma. Henceforth, to reduce this inflammation, anti-inflammatory medication such as prednisone is being administered to Jessica. Prednisolone exhibits peak plasms concentration at around 1 3 hours. Hence, it exhibits maximum anti-inflammatory effect at around 3 hours. From the literature, it is evident that there is no correlation exists between the plasma concentration of prednisolone and clinical response. However, it can be considered that alternate day administration with fluctuating plasma concentrations can be considered as the most effective regimen for the administration of prednisolone. However, in case Jessica, STAT dose of prednisolone is advised because she is exhibiting breathlessness. Breathlessness can occur in Jessica due to bronchoconstriction as a result of inflammation and its medicators. Hence, emergency administration of prednisolone is advised in Jessica. Plasms half-life of prednisolone is 2.1 to 3.5 hours. Hence, it can exhibit its effect upto 10 12 hours (Bergmann et al., 2016). Ipratropium inhalation can be used as broncholytic agent in asthma patients. It can be useful to open the congested respiratory tract in asthma patients. Bioavailability of ipratropium is between 1 6 %. Half-life of inhaled ipratropium is 2 hours. Hence, this drug can produce its effect upto approximately 6 hours after its administration. Ipratropium can be excreted in urine and feces as unchanged and as metabolites. It produces eight metabolites, however none of the metabolites are active as anticholinergic drug. It gets metabolized in inactive ester hydrolysis products. Ipratropium bromide is being given to Jessica for three times with 20 minutes apart duration (Norris Ambery, 2013). Hence, it can be useful in maintaining required concentration for exhibiting broncholytic effect in Jessica. Symptoms: Jessica is showing symptoms line coughing and wheezing. Coughing is the most common symptom of asthma. In asthma patients, cough can be of two types like dry cough and wet cough. In children of Jessicas age, there can be augmented intensity and frequency of cough at the night time. It is called as nocturnal cough (Ng How, 2014; 36-41). Cough have categorized into productive and nonproductive cough. In productive cough, phlegm can be expelled; hence bacteria and other particles can have eliminated from the respiratory tract. Henceforth, it is considered as one of the defense and protective systems of the body. However, majority of the Asthma patients produce non-productive cough which is dry in nature (Niimi et al., 2013; 932-7).. Irritants which are risk factors of bronchoconstriction are mainly responsible for non-productive cough. This bronchoconstriction can be treated by administering bronchodilator like inhaled salbutamol. Salbutamol exhibits its action by acting on the 2 adren ergic receptors and it produces agonist activity on this receptor. There are different types of 2 agonists available and salbutamol is the short acting 2 agonist. In the bronchial smooth muscle of the lung, 2 adrenergic receptors are the major receptors. Agonist activity of the salbutamol results in the 2 adrenergic receptors activation, which further produces activation of the adenyl cyclase enzyme. Adenyl cyclase produces its action by catalyzing conversion of adenosine-tri-phosphate (ATP) to adenosine-mono-phosphate (cyclic AMP). Augmentation of the cyclic AMP exhibits its effect by bronchial smooth muscle relaxation (Busse et al., 2016; 54-64). Airway resistance is also a prominent feature of asthma. Salbutamol reduces intracellular calcium ion concentrations in the airway and reduces airway resistance. Increase in the levels of histamine and leukotriene results in the bronchoconstriction. Cyclic AMP level augmentation can lead to inhibition of release of histamine and leukotrie ne. Hence, it produces relaxation effect of airway by inhibiting bronchoconstrictors like histamine and leukotriene (van Buul, 2015; 1713-25). Wheezing is the whistling sound of exhaled air. Wheezing follows forceful flow of air through the narrow and constricted airways. Chronic inflammation and mucus deposition are mainly responsible for the occurrence of wheezing in asthma patients like Jessica. As a result of airway narrowing and bronchoconstriction, insufficient breathing can occur in patients (Pescatore et al., 2014; 8-13). This inflammation can be treated with anti-inflammatory medication like prednisolone. It exhibits its action by different mechanisms such as : acting on feedback mechanism in immune system, anti-inflammatory and as immune suppressant. As a result, it can be useful in different immune medicated diseases like asthma, rheumatoid arthritis, inflammatory bowel disease and sepsis. It produces its anti-inflammatory action by binding to glucocorticoid receptor (Agache, 2013; 249-56). Through this binding, there is activation of glucocorticoid receptors. Its activation initiates two processes like transacti vation and transrepression. Both transactivation and transrepression are responsible for the anti-inflammatory action of prednisone. Transactivation process produces anti-inflammatory effect by upregulation of different anti-inflammatory genes like lipocortin I, p11/calpactin binding protein, secretory leukoprotease inhibitor 1 (SLPI), and mitogen-activated protein kinase phosphatase (MAPK phosphatase). Transrepression process produces anti-inflammatory action by suppressing expression of proinflammatory proteins in cytosol. It results in the prevention of translocation of transcription factors like NF-B from cytosol to the nucleus (Olin Wechsler, 2014, 349). Critical thinking and rationale: Asthma pathophysiology can be categorized in four different aspects like bronchoconstriction, airway edema, airway hyper responsiveness and airway remodeling. Allergens lead to Immunoglobulin E (IgE) dependent secretions like histamine, leukotrienes and prostaglandins. Mast cells released mediators lead to contraction of airway smooth muscles, narrowing of the airways and bronchoconstriction. Jessica also exhibiting shortness of breath due to bronchoconstriction. Inflammation of the airways is mainly responsible for the bronchoconstriction (Mims, 2015; S2-6). Inflammation of the airways and bronchoconstriction are the main hall marks of asthma. Hence, by administration of bronchodilator like salbutamol there can be improvement in the bronchoconstriction in asthma patient like Jessica. By administration of anti-inflammatory drug like prednisolone there can be improvement in the pathological processes like airway edema, airway hyper responsiveness and airway remodeling. Different inflammatory cells like Th2 lymphocytes, mast cells, eosinophils, dendritic cells, epithelial cells, microphases and resident cells of airway play important role in inflammation of airways. Th2 cytokines such as IL-4, IL-5 and IL-13 contribute for the inflammation in asthma. Mucus hypersecretion and deposition of mucus plugs due to inflammation produce edema in airway which results in the hindrance for flow of air through airways (Doeing Solway, 2013; 834-43). Anticholinergic drug like ipratropium inhalation can act broncholytic agent to open the respiratory tract. By administration of the anti-inflammatory drug like prednisolone, secretion of these inflammatory mediators can be reversed and further consequences of inflammation like bronchoconstriction, airway edema, airway hyper responsiveness and airway remodeling can be prevented. By preventing these pathological changes breathing insufficiency can be improved and coughing and sneezing can be prevented. Airflow limitati on results in the less oxygen saturation in Jessica. To compensate, less oxygen saturation, Jessica is being supplemented with artificial oxygen with flow rate of 10 - 15L/minute via face mask (Bergmann, 2014; 69-80; West et al., 2013). Medications administered to Jessica can be useful to produce either symptomatic relief or can be useful in the acute stage. Hence, in chronic stage of asthma varied pathological changes like airway hyperresponsiveness subsequent to the chronic inflammation and structural changes can occur. Hypertrophy and hyperplasia of the airways and lungs can occur due to chronic inflammation. Airway remodeling results in the structural and pathological alterations in the respiratory tract followed by chronic inflammation. It results in the loss of lung function. Airway remodeling produces structural cells activation in the airway, structural alterations of cells in the airway and airway responsiveness alterations. Airway remodeling produces changes like sub-basement membrane thickening, subepithelial fibrosis, hypertrophy and hyperplasia of airway smooth muscle, proliferation and dilation of blood vessels, mucous gland hyperplasia and hypersecretion. Airway remodeling reflects persistent, chronic and progressive feature of the asthma. Airway narrowing and airway modeling results in the forceful flow of air through the airways which can produce coughing and wheezing in the asthma patients. Due to airway narrowing and airway modeling, there is forceful passage of air through airways of Jessica. In Jessica also, this forceful passage of air lead to coughing and sneezing (Bonini Usmani, 2015; 281-93). Hence, it is necessary to administer medications to recover from the airway remodeling. Conclusion: Asthma is a multifactorial disease due to different risk factors and varied symptoms. Symptoms of asthma can be prevented by averting exposure to risk factors like allergens and irritants. Coughing and wheezing are the prominent symptoms of asthma; however, these are also associated with other respiratory diseases. Hence, accurate diagnosis need to be performed for providing specific treatment and management of asthma. Pathological changes in asthma comprises of sequential events like inflammation, edema, bronchospasm, and remodeling. Pathological changes like inflammation and bronchospasm can be treated with medications like anti-inflammatory drugs and bronchodilator inhalation. Multiple mechanisms are involved in the pathogenesis of asthma; hence it exhibits different symptoms. All these mechanisms can not be targeted by using single drug and all these symptoms can not be treated by using single drug. Hence, research need to be carried to develop drug with multiple effects on varie d mechanisms of asthma. In summary, more research is required for providing complete treatment to asthma patients. References: Agache, I.O. (2013). From phenotypes to endotypes to asthma treatment. Current Opinion In Allergy and Clinical Immunology, 13(3), 249-56. https://insights.ovid.com/allergy-clinical-immunology/coaci/2013/06/000/phenotypes-endotypes-asthma-treatment/6/00130832. Bergmann, T.K., Barraclough, K.A., Lee, K.J., Staatz CE. (2012). 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