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Running head: PATHOPHYSIOLOGY AND PHARMACOLOGY PATHOPHYSIOLOGY AND PHARMACOLOGY Name of the student: Name of the university: Author note:
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1PATHOPHYSIOLOGY AND PHARMACOLOGY Pathophysiology and link with the case study: Asthmahas emerged as a leading cause of respiratory illness that impacted more than thousandsofindividualseachyear.InAustralia,approximately2.7millionpopulation experienced mild to severe asthma in 2018 which resulted in the increased expenditure of health care (Tay, Abramson,& Hew 2016). The case study involves a 32-year-old man, Mr Rogar Wilson with a history of asthma who was complaining regarding shortness of breath, fever, and productive cough and headache. He was identified with a respiratory infection and his chest Xray exhibit bilateral pneumonia. Considering the pathophysiology of bilateral pneumonia,due to bacterial or viral infection, the alveoli’s become inflamedand filled with fluid which resulted in breathingdifficulties.Thecommoncausativeagentsofthebilateralpneumoniaare Streptococcus pneumonia, Haemophilus influenza, Legionella pneumophilaandMycoplasma pneumonia(Yinetal.,2016).Ontheotherhand,virusessuchasInfluenzaAandB, coronaviruses and adenoviruses can be the causative agent of pneumonia. The common risk factors for developing bilateral pneumonia include the history of asthma, weakened immune system,smoking andpresence of lungsor heartdisease(Daviset al.,2017). The case studyhighlighted that Mr roger has diagnosed with a respiratory tract infection which might be the reason behindairway inflammation as infection,pollen and tobacco are the environmental triggers that can induce airway inflammation followed by obstruction of airflow. As discussed by Teo et al. (2018), a bacterial infection in the lungs negatively impacted mucociliary clearance and facilitatemucousproductionin thelungs. The rapidmucousproductionresultedin inflammation of the lower airway. The case study suggested that Mr Rogar experienced productive cough over the past week. At this juncture, it can be said that mucous production resulted in the obstruction of airway and swelling of airway lining. Moreover, the productive
2PATHOPHYSIOLOGY AND PHARMACOLOGY mucous contain cellular debris, inflammatory cells like leukocytes and epithelial cells that can trigger the inflammation and block the air tubes of the patients (Teo et al., 2017). The case study highlighted that the patient experiencedFlu-like symptoms, sore throat andrespiratory infection while converting a warehouse into the gym. The pathophysiology can be explained from the immunological perspective.Fanet al. (2016), suggested that when antigen or allergen (smoke, pollen, bacterial and viral particle) detected in the body, the immune system responded to the detected allergen by secreting IgE antibody that binds to the antigen. The binding of IgE antibody and antigen resulted in degranulation of immune cells such as basophil and mast cells (Baxter, Clothier & Perrett, 2018). These cells degranulated to release prostaglandin D2 and histamines which increase the blood flow. The degranulation also releases facilitate smooth muscle constriction as well as mucous secretion. The process is known as IgE mediated type I hypersensitivity.Silver et al. (2018),suggested that patients with asthma often experience bilateral pneumonia since they are sensitive to the environmental triggers and experience frequent inflammatory responses followed by shortness of breath. Consequently, the patient experienced shortness of breath, headaches and a productive cough over the past week. On the other, persistent difficulties in the breathing, chest pain, cough and fever altered the vital signs of the patients and subjected the patient to the anxiety and distress. The detailed explanation of the vital signs of the patient will be explained in details in the following section. Discussion of threerelevant signs and/or symptoms of the patient: As discussed in the case scenario, a patient diagnosed with a respiratory infection and X- ray report highlighted bilateral pneumonia which resulted in discomfort. At this juncture, the three most relevant clinical manifestations exhibited by Mr Roger Wilson are shortness of breath, chest pain and tachycardia.
3PATHOPHYSIOLOGY AND PHARMACOLOGY Shortness of breath: Shortness of breath is considered as one of the most common clinical manifestations exhibited by the patients experiencing asthma or bilateral pneumonia. In this context, the difficulty of breathing exhibited by the patient due to respiratory infection and history of asthma which resulted in the inflammatory response and airway obstruction followed by mucous production (Benkouiten,Al-Tawfiq,Memish, Albarrak & Gautret, 2019). The case study suggested that the patient had a history of asthma and experienced productive cough formation in the past two weeks, highlighting that productive cough formation might be the contributing factors behind shortness of breath. The breathlessness further resulted in increased respiratory of the patient.On admission, his respiratory rate was 31 breaths/minute whereas the normal respiratory rate is 12 to 24 breaths/minute, indicating that he has an elevated respiratory rate (Cardona-Morrell et al., 2016).Likewise, the oxygen saturation of the patient was also low which might be the reason behind shortness of breath. The oxygen saturation of the patient also dropped to 92% whereas normal oxygen saturation for the healthy individual is 98% (Cardona- Morrell et al., 2016).The low oxygen saturation is observed when lungs of the patients unable to inhale oxygen due to the production of mucous and transport to the cells and tissues (Berliner, Schneider, Welte & Bauersachs, 2016). Consequently, oxygen saturation of the patient decreased followed by lungs damage and other organ damages. Therefore, the shortness of breath resulted in distress and anxiety as observed in the case of Mr Rogar. Chest pain: Chest pain or pleuritic chestpain characterized by sudden stabbing pain or intense pain in the chest during inhalation and exhalation. pleuritic chest pain is considered as the most common clinical manifestation ofpneumonia which usually caused byinflammation of the partial pleura.
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4PATHOPHYSIOLOGY AND PHARMACOLOGY However, other etiological factors are also present behind the development of chest pain. Holland and Holland (2019),suggested that the chest pain in pneumonia usually exhibited due to muscle strains because of excessive coughing. The chest pain also observed due to inflammation of the airway lining caused by bacteria infection as observed in this case scenario. When the chest wall moves during breathing, pleura moves which induced a sense of pain (Nguyen , 2018). The pain usually worsens during breathing difficulty as breathing difficulty increases inhalation and exhalation. While chest pain results from a viral infection or bacterial infection in the respiratory tract, it can be caused by pulmonary embolism where blood clot obstruction hinders the normal flow of blood into the lungs. Even though the patient described his pain score 2 out of 10, it can increase gradually if remain unresolved. In this context, in order to conduct further diagnosis, these factors are required to consider for avoiding erroneous diagnosis. Tachycardia: The patients with bilateral pneumonia and history asthma frequently exhibit elevated pulse rate or tachycardia. As discussed byAshok, Cabalag and Taylor (2017),the patients with severe breathing difficulties often have low oxygen saturation. The underlying reason is the mucous production resulted in inflammation of lungs and low oxygen saturation. The inadequate oxygen saturation in the blood increases the oxygen demand of the body. In order to address the oxygen demand of the body, the heart pumps harder than the typical capacity to transport the oxygen to cells and tissues and it increases the heart of the patient as observed in this case study (Anderson et al, 2019). On admission, the pulse rate of the patient was elevated compared to the normal pulse rate. The vital sign assessment suggested that pulse rate was 128 beats per minute whereas the normal pulse rate for the healthy individual is 60 to 100 beats per minute (Cardona- Morrell et al., 2016). The blood pressure of the patient also reduced due to the tachycardia. The
5PATHOPHYSIOLOGY AND PHARMACOLOGY vital sign assessment suggested that his blood pressure 100/60 mmHg whereas the normal blood pressure for the healthy individual is120/80 mmHg (Cardona-Morrellet al., 2016). Therefore, properpharmacologicalsupportmustbeprovidedforbettermanagementofthehealth condition. Three pharmacological drugs and role in reducing symptoms: The case study suggested thatclinical manifestations exhibited by Mr Roger Wilson are shortness of breath, chest pain and tachycardia. The medical orders suggested that Mr Roger Wilson was provided with benzylpenicillin intravenously, Doxycycline and Salbutamol via nebulizer. Benzylpenicillin 1.2g: Benzylpenicillin is a narrow-spectrum antibiotic used for treating bacterial infection. It is usually provided to patients intravenously for reducing bacterial infection during pneumonia as observed in this case study Due to poor oral absorption, it is intravenously provided to the patients for addressing the infection. Pharmacodynamics: It is a beta-lactam antibiotic used for treating bacterial infections triggered by gram- positive organisms. Considering the pharmacodynamics of the drug, it specifically binds to penicillin-binding proteins (PBPs) present in the cell wall of the bacteria. After binding, the drug inhibits the the bacterial cell wall synthesis (Hand et al., 2019). The cell lysis further mediated by autolytic enzymes such as autolysins as the drug binds to the autolysin inhibitor. The drug is resistantagainsthydrolysisprocessmediatedbyarangeofdifferentenzymessuchas penicillinases. Pharmacokinetics:
6PATHOPHYSIOLOGY AND PHARMACOLOGY The pharmacokinetics can be explained using the ADME principle. Absorption:In case of intramuscular and subcutaneous injection, it is rapidly absorbed by the bodywhereinitialbloodlevelsarehigh.Whilethebioavailabilityoftheintravenous administration is 100%, the bioavailability of the oral administration is 15 to 30% (Bos et al., 2018). The volume of distribution: with the normal renal function, it is 0.53–0.67 L/kg. Protein binding:approximately 45 to 68% of the drug attached to serum protein, especially albumin(Bos et al., 2018). Metabolism: 30% of the drug metabolized into the penicilloic acid and a small amount of 6-aminopenicillins acid which is observed in the urine of the patient. The small portion is hydroxylated into one or more activate metabolites (Bos et al., 2018). Route of elimination:the route of elimination is eliminated by Kidney through urination. Some of the drugs are eliminated through biliary excretion. Doxycycline: It is a tetracycline antibiotic that fights bacteria of the body. In this context, as the patient was experiencing respiratory infection, Doxycycline was provided to the patient for reducing respiratory tract infection followed by chest pain and tachycardia. Pharmacodynamics: Unlike the previous antibiotic, it is a bacteriostatic antibiotic that inhibits the protein synthesis of the bacteria by attaching to the 30S ribosomal subunit, especially 16 sRna portion of
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7PATHOPHYSIOLOGY AND PHARMACOLOGY the ribosomal subunit. Therefore, the inhibition further prevents the binding of tRNA to RNA- 30S bacterial ribosomal subunit followed by inhibiting protein synthesis (Hopkins et al., 2016). Pharmacokinetics: The pharmacokinetics can be explained using the ADME principle. Absorption:Rapidly absorbed while orally administrated and highly soluble in nature. The peak serum level of approximately 2.6 mcg/ml within 2 hours (Zhang et al., 2019). The volume of distribution:it diffuses readily into the body tissues and body fluid with 0.7 L/kg. The protein binding is approximately less than 90% with the plasma protein. Metabolism: it is metabolized in the GI tract and liver (Zhang et al., 2019). Route of elimination: the drug mainly eliminated through the urine as well as faeces as unchanged drug. Approximately 40% to 60% ofdose is eliminated through urine within 92 hours. Salbutamol: Salbutamol is a bronchodilator that provided to the patients with pneumonia for reducing shortness of breath. In this context, since the patient was facing shortness of breath, Salbutamol via nebulizer was provided for reducing the shortness of breath. Pharmacodynamics: Salbutamol is a bronchodilator that reduces airway constriction by opening the passage of the lungs and facilitate normal airflow. Salbutamol is moderately selective beta (2)-receptor agonist that facilitate airway smooth muscle relaxation followed by Broncho-dilation of the patient. At the therapeutic dose, it exhibits actions on beta2- adrenoceptors of bronchial muscle for stimulating bronchodilation and stimulation (Moore et al., 2019). Pharmacokinetics:
8PATHOPHYSIOLOGY AND PHARMACOLOGY Pharmacokinetics can be described by ADME principle. Absorption:salbutamol display actions on smooth muscle, weakly bound to plasma protein. The peak plasma absorption is about 3 mg/mL within 2 to 3 hours (Vet et al., 2020). The volume of distribution:The volume of distribution of salbutamol is 156 +/- 38 L. Metabolism:considering the metabolism, it is digested in the liver and it convert into salbutamol 4'-O-sulfate. In a few cases, it undergoes oxidative deamination for acting as a bronchodilator Route of elimination:Within 24 hours, roughly 72% of the inhaled dose is excreted in the urine and 28% of them were unchanged drugs (Moore, Riddell, Joshi, Chan& Mehta, 2017). A small fraction of it eliminated through feces.
9PATHOPHYSIOLOGY AND PHARMACOLOGY References: Anderson, R. D., Lee, G., Prabhu, M., Patrick, C. J., Trivic, I., Campbell, T., ... & Kumar, S. (2019). Ten‐year trends in catheter ablation for ventricular tachycardia vs other interventionalproceduresinAustralia.Journalofcardiovascular electrophysiology,30(11), 2353-2361.https://doi.org/10.1111/jce.14143 Ashok, A., Cabalag, M., & Taylor, D. M. (2017). Usefulness of laboratory and radiological investigationsinthemanagementofsupraventriculartachycardia.Emergency Medicine Australasia,29(4), 394-399.https://doi.org/10.1111/1742-6723.12766 Baxter, C. M., Clothier, H. J., & Perrett, K. P. (2018). Potential immediate hypersensitivity reactionsfollowingimmunizationinpreschoolagedchildreninVictoria, Australia.Humanvaccines&immunotherapeutics,14(8),2088-2092. https://doi.org/10.1080/21645515.2018.1460293 Benkouiten, S., Al-Tawfiq, J. A., Memish, Z. A., Albarrak, A., & Gautret, P. (2019). Clinical respiratory infections and pneumonia during the Hajj pilgrimage: A systematic review.Travelmedicineandinfectiousdisease,28,15-26. https://doi.org/10.1016/j.tmaid.2018.12.002 Berliner, D., Schneider, N., Welte, T., & Bauersachs, J. (2016). The differential diagnosis of dyspnea.DeutschesÄrzteblattInternational,113(49),834. .doi:10.3238/arztebl.2016.0834 Bos, J. C., van Hest, R. M., Mistício, M. C., Nunguiane, G., Lang, C. N., Beirão, J. C., ... & Prins, J. M. (2018). Pharmacokinetics and pharmacodynamic target attainment of benzylpenicillininanadultseverelyillsub-SaharanAfricanpatient
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11PATHOPHYSIOLOGY AND PHARMACOLOGY Hopkins, A. M., Wojciechowski, J., Abuhelwa, A. Y., Mudge, S., Upton, R. N., & Foster, D. J. (2017). Population pharmacokinetic model of doxycycline plasma concentrations using pooled study data.Antimicrobial agents and chemotherapy,61(3), e02401-16. t https://doi.org/10.1128/ AAC.02401-16. Moore, A., Riddell, K., Joshi, S., Chan, R., & Mehta, R. (2017). Pharmacokinetics of salbutamol delivered from the unit dose dry powder inhaler: comparison with the metered dose inhaler and Diskus dry powder inhaler.Journal of aerosol medicine andpulmonarydrugdelivery,30(3),164-172. https://doi.org/10.1089/jamp.2015.1277 Nguyen, D. N., Tran, C. D., Rudkin, S. M., Mueller, J. S., & Hartman, M. S. (2018). Epipericardial fat necrosis: uncommon cause of acute pleuritic chest pain.Radiology case reports,13(6), 1276-1278. https://doi.org/10.1016/j.radcr.2018.09.007 Silver, J. D., Sutherland, M. F., Johnston, F. H., Lampugnani, E. R., McCarthy, M. A., Jacobs, S. J., ... & Newbigin, E. J. (2018). Seasonal asthma in Melbourne, Australia, andsomeobservationsontheoccurrenceofthunderstormasthmaandits predictability.PloS one,13(4).doi:10.1371/journal.pone.0194929 Tay, T. R., Abramson, M. J., & Hew, M. (2016). Closing the million patient gap of uncontrolledasthma.MedJAust,204(6),216-7. https://www.mja.com.au/system/files/issues/204_06/10.5694mja15.01141.pdf Teo, S. M., Tang, H. H., Mok, D., Judd, L. M., Watts, S. C., Pham, K., ... & Bochkov, Y. A. (2017). Dynamics of the upper airway microbiome in the pathogenesis of asthma- associatedpersistentwheezeinpreschoolchildren.BioRxiv,222190.doi: https://doi.org/10.1101/222190
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