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Mr Roger Wilson is a 32-year-old man with a history of asthma who is currently a gym instructor, had seen his GP complaining of shortness of breath, fever, headaches and a productive cough over the past week. The GP has diagnosed Mr Wilson with a respiratory tract infection and has prescribed roxithromycin (Rulide) 150mg twice daily (BD). After taking the antibiotic for two (2) days, Mr Wilson has returned to his GP feeling much worse. A chest x-ray shows bilateral pneumonia and Mr Wilson was administered to hospital via the emergency department (ED).


Roger has a history of mild asthma, which he has had since childhood. His symptoms often get worse with exercise and he takes salbutamol (Ventolin) via a metered dose inhaler (MDI) for symptom relief. Over the past few months, Roger and his partner, Matthew, have been converting an old warehouse into a gym. During this time, both of them developed ‘flu-like’ symptoms, sore throats and chest infections. Upon arrival to the ED, Roger appears anxious and breathless.

On admission to the ED, Roger is sweating (diaphoretic) and flushed. He is alert and orientated but very breathless, with slight chest pain, which he rates as a two out of 10 on a numerical pain scale. He has a productive cough with green and malodorous sputum. Roger has never smoked and drinks only socially.

• Identify three (3) appropriate signs/symptoms as related to the patient in the case study.
• Accurately explain these three (3) signs/symptoms as related to the patient in the case study.
• Display a clear, succinct understanding of the signs/symptoms and their connection to the pathophysiology of disease as appropriate to the patient in the case study.
• Identify three (3) relevant pharmacological (medications) interventions as presented in the case study.
• Accurately explain these three (3) medications as related to the patient in the case study.
• Display a clear, succinct understanding of the signs/symptoms and their connection to the pharmacology of disease as appropriate to the patient in the case study - including discussion regarding ADME.
 

Symptoms and Anatomical Structures Associated with Bilateral Pneumonia

The clinical scenario is based on Mr. Roger Wilson, a 32 year old man admitted to the emergency department (ED) with symptom of breathlessness, chest pain and cough. He has been diagnosed with respiratory tract infection (RTI) and chest x-ray shows bilateral pneumonia. It is a type of acute lower respiratory tract infection affecting both the lungs and leading to symptom of headache, sneezing, breathlessness, tight feeling in the chest and productive cough (Fabbri et al., 2017). The review of the case study shows that Roger also has similar symptoms. The anatomical structure that is mostly affected for Roger includes the lungs and the alveoli. Because of this, the patient is suffering from slight chest pain, productive cough and breathlessness. This is in relevance with the anatomy and physiology of the disease because during bilateral pneumonia, inflammation of the alveoli takes place and it becomes filled with pus leading to symptom of breathlessness (McCauley & Dean, 2015).The change in physiology of the lungs due to bacterial or viral infection leads to breathing difficulty and wheezing (Craft & Gordon, 2019). Structural changes in the lung is seen due to direct invasion of bacteria in the pleural space and initiation of cascade of inflammatory events (Quinton, Walkey & Mizgerd, 2018).

The anatomy of bilateral pneumonia and physiology is linked to the pathophysiology behind the disease of the patient in the case study too. Understanding pathophysiology behind the disease is also critical to understand the rationale behind a pharmacological regimen for Mr. Roger. Direct bacterial invasion, inflammation in the lungs and pleural space, cascade of inflammatory events and bacteriologic virulence features are some of the pathophysiology behind the disease (Quinton, Walkey & Mizgerd, 2018). Mr. Roger has experienced episodes of shortness of breath and productive cough. This has occurred because of the pathophysiological process associated with bilateral pneumonia. Pneumonia is mainly caused by viral or bacterial infection. The process of inflammation of the air sacs in the lung occurs due to initiation of an immune response in the lung following invasion by bacteria or virus. Acceleration of the immune response contributes to fluid loculation. This occurs by migration of the neutrophil and activation of the coagulation cascade leading to fluid within the alveoli. As the protein rich fluid accumulates in the alveoli, the mucus plugs reduces the efficiency of gas exchange in the lungs. The alveoli are further filled with fluid resulted in impaired gas exchange and risk of continued infection (McCauley & Dean, 2015). These pathophysiological changes might be the reason for clinical manifestation of pneumonia for Mr. Roger and it is linked to anatomical structures associated with pneumonia too as changes in the lung structures initiates cascade of inflammatory events and causes accumulation of fluids (Gon & Hashimoto 2018).   

Pathophysiology of Bilateral Pneumonia and its Clinical Manifestations


Management of bilateral pneumonia is mainly dependent on pharmacological treatment. Treatment is also dependent of type of infection and the main goal is to reduce the symptoms associated with impaired gas exchanged and breathing difficulty for patient. The pharmacology of the prescribed pharmacology for Mr. Roger can help to understand how the drug is going to act in the body of patient. Antibiotic is the main frontline therapy for management of pneumonia. IV Benzylpencillin is a narrow spectrum antibiotic that has been provided to Roger and it is prescribed mainly to treat bacterial infection in patients with pneumonia. It is administered intravenously due to poor oral absorption and the drug works by binding to penicillin binding proteins within the bacterial cell wall. In this way, it inhibits the last stage of bacterial cell wall synthesis leading to cell lysis (Drug Bank, 2018). Evidence suggests that benzyl penicillin is an appropriate pharmacological option for treatment of patient with pneumonia. Early use of this medication provides many benefits such as reduced demand for nursing care, elimination of injectable medications and low cost of treatment (Agweyu et al., 2014). Hence, use of Benzylpenicillin can hasten recovery by reducing progression of infection and preventing complications for Mr. Roger.

Another medication prescribed to Roger for first day includes Doxycyline. The main rationale behind giving this medication is that it also works to prevent growth of bacteria and thus treat infection. It belongs to the drug class tetracycline antibiotics and it is used to treat different types of bacterial infection. It also has similar course of action like that of benzylpencillin and it inhibits protein synthesis by binding to the 30S ribosomal unit.  This results in inhibition of bactetial growth and consequently improvement in symptoms of patient (Nightingale & Bishai, 2016). In response to history of mild asthma, Mr. Roger takes Salbutamol via metered dose inhaler (MDI). Salbutamol is a short acting beta2adgrenergic receptor agonist used in the treatment of asthma. Evidence suggests that β2?Adrenoceptor agonists and glucocorticoids are the most effective pharmacological options for the treatment of airway inflammation. It is part of first line therapy for asthma. β2?Adrenoceptor agonists are most vital drug class for the treatment of asthma. Short acting preparations like salbutamol is provided on need basis and long-acting preparation in combination with glucocorticoid is used for long-term treatment (Amrani & Bradding 2017). This pharmacological treatment is linked to treatment of bronchocontriction for Mr. Roger because this class of drug has bronchodilator effect and they play a role in relieving breathlessness.   

Pharmacology of Prescribed Medications for Bilateral Pneumonia

The three dominant symptoms of bilateral pneumonia that has been found in Mr. Roger includes breathlessness, productive cough and chest pain. These three symptoms are some of the clinical manifestation of pneumonia too. These three symptoms are connected with the pathophysiology of bilateral pneumonia as pathophysiology changes in response to bacterial invasion and inflammatory response contributes to manifestation of such symptoms (Fabbri et al., 2017). For example, productive cough and mucous is most common symptom seen in patients with bilateral pneumonia. Productive cough was one of the symptoms for Roger and this has links with the pathophysiology of bilateral pneumonia as cough is produced in response to lower respiratory tract infection. Productive cough is a sign of acute bacterial infection and severe allergic reactions. This results in deposition of thick mucus plugs that blocks the airway (Begic et al., 2017). During admission to the ED, Mr. Roger had a productive cough with green and malodorous sputum. This symptom is seen because of airway mucus hypersection caused due to pathophysiological manifestation of the disease. Under normal condition, the main function of mucous is to protect the airway by moistening the air. However, anaerobic infection of the lungs leads to purulent cough (Shen et al. 2018). As this can limit airflow, appropriate pharmacological management is necessary for pneuomonia patients like Roger.

Breathlessness or dyspnea is one of the symptoms observed for Mr. Roger. The case study revealed that shortness of breath was a problem he was facing over the past week. This symptom is also directly linked to the pathophysiology of pneumonia. Breathlessness is caused in pneumonia following bacterial infection as the inflammatory cascade results in release of macrophage and filling up of the inner linings of the alveolar space with fibrin rich exudates. This renders the alveolar space airless causing pulmonary edema and impaired lung expansion. Reduced gaseous exchange is the common cause behind oxygen deprivation and increased work of breathing (Regunath & Oba, 2018).Hence, as airflow obstruction increase, increase in breathing effort lead to symptom of breathlessness. Coccia et al. (2016) explains that increased work of breathing or breathlessness results because of activation of several pathway. The condition is mostly perceived as tightness and increased respiratory work effort.

The review of the clinical scenario of Mr. Roger also showed that he experienced slight chest pain with breathlessness. The intensity of pain was low as the pain score as per patient’s response was two out of ten. This symptom was seen because of muscle strain due to excessive coughing or by acute inflammation in the inner linings of the lung. Chest pain may accompany only during the progression of airway inflammation. Pleural chest pain is mainly linked to inflammation of the parietal pleura and the release of the inflammatory mediators in the pleural space triggers pain receptors. Trauma in the rib cage and the intercostals nerves leads to pain localized in the cutaneous distribution of nerves (Reamy, Williams & Odom, 2017). There are many cause behind such pulmonary embolism and in case of Roger, it is linked to bilateral pneumonia.  

Importance of Salbutamol in the Treatment of Bilateral Pneumonia

Salbutamol via nebulizer, IV benzylpenicillin and Doxcycline are the three medications that has been prescribed to Mr. Roger for symptom relief and treatment of asthma. The main goal of providing Salbutamol is to achieve symptom relief by the suppression of airway inflammation and decrease of bronchial hyper-responsiveness. It is important to provide Salbutamol to Mr. Roger because his symptoms reflect acute infection due to bilateral pneumonia.. Another rationale behind prescribing Salbutamol is that it is a short acting beta 2 adrenergic agonist. Hence, it can initiate action quickly. The rational for providing Salbutamol to patient is also understood from the review of pharmacokinetics and pharmcodynamics of the medication. The understanding regarding absorption, distribution, metabolism and excretion (ADME) can give idea regarding how quickly the medication can provide relief to Mr. Roger.

The review of the pharmacodynamics of Salbutamol can help to interpret the mechanism of action of the drug. As it is a beta 2 beta 2 adrenergic agonist, it works by inducing bronchodilator effect by activating adrenergic receptors. It initiates cascase of pathway leading to AMP release and increase in calcium ion concention thus causing symptom relief (Neame et al., 2015). In addition, the pharmacokinetics details the duration by which above mentioned action is accomplished (Bryant & Knights, 2019). The half life of salbutamol is 4 to 6 hours. After inhalation, the medication acts on bronchial smooth muscles and the concentration of the drug lowers after 2-3 hours. After this. the drug is absorbed in the gut. The bronchodilatory effect of the drug is seen at blood concentration of 5-20 ng/ml. The medication is mostly distributed to the lungs as unmetabolised drugs and the rest is deposited in oropharynx. Although Salbutamol is not metabolized in the lungs, however it is converted to salbutamol 4’-O-sulfate. Salbutamol and its metabolites are excreted in the urine. Hence, elimination half life is 5.5 hours post inhaled or oral administration.  The renal clearance of the drug depends on mode of administration. After oral administration, renal clearance takes place as 38ml/min and for intravenous administration, it is 70 ml/min (Drug Bank 2018). This explains the pharmacokinetic properties of Salbutamol and how quickly Salbutamol is going to provide relief to Mr. Roger. The prescribed drug is linked to pathophysiology as it works to address bronchoconstriction occurring due to airway inflammation for asthma patient.

The second medication that was prescribed to Mr. Roger included IV Benzylpenicillin. As Mr. Roger was experiencing breathlessness and increased work of breathing, Benzylpenicillin was prescribed to him to improve breathing. Benzylpenicillin is an antibiotic that is used to treat variety of bacterial infection. It is a narrow spectrum antibiotic that is administered intravenously because of poor oral absorption. It is a penicillin beta-lactum antibiotic used in treating infections cause of gram positive bacteria. The bactericidal effect is seen because of the inhibition of cell wall synthesis and binding of the drug with penicillin binding protein (Waller & Sampson, 2017). By this form of binding, it inhibits cell wall synthesis and lead to cell lysis. Antibiotics is the common drug given to patients with bilateral pneumonia. Hence, Benzylpenicillin has been prescribed to Mr. Roger to treat productive cough and malodorous sputum. The quick action of Benzylpenicillin is understood from rapid absorption of drug. After distribution to lungs, the drug is metabolized to penicilloid acid which is an inactive metabolite. The drug is eliminated via kidney and half life is 0.4 to 0.9 hours (Ajavon & Taft, 2016). With links to pathophysiology, the drug works to address the issue of mucus hypersecretion occurring during bacterial infections and lung inflammation. 


The review of medical orders of Mr. Roger also revealed that he had been prescribed Doxycycline. Doxycycline is also an antibiotic used to treat various form of infection. Mr. Roger has been prescribed Doxycycline due to its immune suppressing effects. Bhattacharyya et al. (2017) proves that long term use of the drug helps in symptom improvement and improvement in the obstructive parameters of pneumonia. Hence, Roger has been prescribed this medication to promote lung function and reduce chronic respiratory obstruction which is a part of the pathophysiology of bilateral pneumonia.

The review of pharmacodynamics of Doxycycline can indicate what properties of the drugs serves to establish therapeutic effect on patient. Its bactericidal action is seen because of the inhibition of bacterial protein synthesis binding to the 30S ribosomal subunit. By inhibiting protein synthesis, it stops replication of bacteria and contribute to bacteriostatic effect (Xing et al., 2015). The review of ADME indicates why fixed dose of the drug is being given to Mr. Roger.  It is readily absorbed after oral administration and metabolized in the gastrointestinal tract. The drug is mainly excreted via urine and faeces and the half life is about 16.33 hours. The clearance of the drug takes place via kidney. The combination of three drugs is likely to provide relief from current symptoms for Roger and reduce the likelihood of exacerbation in the future too (Drug Bank 2018). 

References:

Agweyu, A., Gathara, D., Oliwa, J., Muinga, N., Edwards, T., Allen, E., ... & Awuonda, B. (2014). Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial. Clinical infectious diseases, 60(8), 1216-1224. https://doi.org/10.1093/cid/ciu1166

Ajavon, A. D., & Taft, D. R. (2016). 4 Pharmacokinetics/ADME of Small Molecules. Preclinical Drug Development, 71. Retrieved from: https://books.google.co.in/books?hl=en&lr=&id=HFnvBQAAQBAJ&oi=fnd&pg=PA71&dq=ADME+OF+Benzylpenicillin&ots=KjBC5q2Wwe&sig=GitjPZC05ZeoRtH-6tz8I7Uvph0#v=onepage&q=ADME%20OF%20Benzylpenicillin&f=false

Amrani, Y., & Bradding, P. (2017). β2-Adrenoceptor Function in Asthma. In Advances in immunology (Vol. 136, pp. 1-28). Academic Press. Retrieved from: https://lra.le.ac.uk/bitstream/2381/40466/6/GPCR-b2%20receptor%20Chapter%202017%20Final.pdf

Begic, E., Begic, Z., Dobraca, A., & Hasanbegovic, E. (2017). Productive Cough in Children and Adolescents - View from Primary Health Care System. Medical archives (Sarajevo, Bosnia and Herzegovina), 71(1), 66-68. doi: 10.5455/medarh.2017.71.66-68

Bhattacharyya, P., Sarkar, S., Das, S., & Saha, D. (2017). Long term effect of doxycycline in asthma: a real world observation. European Respiratory Journal 2017 50 (61), DOI: 10.1183/1393003.congress-2017.PA4686

Bryant,B.,& Knights,K.(2019)Pharmacology for health professionals(5th ed.)New South Wales, Australia: Elsevier

Coccia, C. B., Palkowski, G. H., Schweitzer, B., Motsohi, T., & Ntusi, N. A. B. (2016). Dyspnoea: Pathophysiology and a clinical approach. SAMJ: South African Medical Journal, 106(1), 32-36. DOI:10.7196/SAMJ.2016.v106i1.10324

Craft,J,& Gordon,C.(2019). Understanding pathophysiology (ANZ 3rd.ed). New South Wales, Australia: Elsevier. Retrieved from: https://www.elsevier.com/books/understanding-pathophysiology-anz/craft/978-0-7295-4264-7

Drug Bank (2018). Benzylpenicillin. Retrieved from: https://www.drugbank.ca/drugs/DB01053

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McCauley, L., & Dean, N. (2015). Pneumonia and empyema: causal, casual or unknown. Journal of thoracic disease, 7(6), 992. 10.3978/j.issn.2072-1439.2015.04.36

Nightingale, C. H., & Bishai, W. R. (2016). The Role of Macrolides in the Treatment of Community-Acquired Pneumonia. In Community-Acquired Respiratory Infections(pp. 66-79). CRC Press. Retrieved from: https://www.taylorfrancis.com/books/e/9780203912140/chapters/10.3109/9780203912140-9

Quinton, L. J., Walkey, A. J., & Mizgerd, J. P. (2018). Integrative physiology of pneumonia. Physiological reviews, 98(3), 1417-1464. https://doi.org/10.1152/physrev.00032.2017

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Regunath, H., & Oba, Y. (2018). Pneumonia, community-acquired. In StatPearls [Internet]. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK430749/

Shen, Y., Huang, S., Kang, J., Lin, J., Lai, K., Sun, Y., Xiao, W., Yang, L., Yao, W., Cai, S., Huang, K., … Wen, F. (2018). Management of airway mucus hypersecretion in chronic airway inflammatory disease: Chinese expert consensus (English edition). International journal of chronic obstructive pulmonary disease, 13, 399-407. doi:10.2147/COPD.S144312

Waller, D. G., & Sampson, T. (2017). Medical pharmacology and therapeutics E-Book. Elsevier Health Sciences. Retrieved from: https://dspace.fue.edu.eg/xmlui/bitstream/handle/123456789/1757/9327.pdf?sequence=1

Xing, R., Witsø, I. L., Jugowiec, D., Tiainen, H., Shabestari, M., Lyngstadaas, S. P., ... & Haugen, H. J. (2015). Antibacterial effect of doxycycline-coated dental abutment surfaces. Biomedical Materials, 10(5), 055003. doi:10.1088/1748-6041/10/5/055003  

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