• Internal Code :
  • Subject Code : NURS 2003
  • University :
  • Subject Name : Nursing

Case Study: Brian Fuller

Q.1. The patient in the case study is having a history of hypertension and hypercholesterolemia. This can be a major cause of fat deposition in the major arteries. In the case of hypertension, the patients are usually having a high systolic blood pressure reading. This blood pressure leads to the increase of internal pressure in the arteries and thus bringing about dynamic changes in them (Weiss, 2016). The fat deposition is the main reason to cause the occlusion of the blood flow in major arteries and thus constraining the easy commute of blood through them. Over the due course of time, a blood clot may develop that might restrict the flow altogether, leading to the patient having an episodic event of a stroke. The narrowed arteries severely block the blood flow and also adds up to the tension in the vessels (O'Neal, 2016). The plague formation is also bound to cause small or large clots. These clots might get dislodged leading to their flow in their major bloodstream. Patients having an episode of stroke are usually observed to have an elevated blood pressure reading.

While in acute cases, the blood pressure usually subsides within a few hours of the incidence. This elevation in the blood pressure readings is bound to cause an improvement in cerebral perfusion to the ischemic tissue. This helps in reducing the underlying cerebral edema caused by the manifestation of the disease in the patient (Hermida, 2016). This is also helpful in preventing the tissue transformation of the ischemic tissue. The risk factor is of a greater gravity in the individuals that are of an advancing age such as given in our case study. The main interventions that are generally used in such scenarios are usually based on lowering the blood pressure in the patient. This is also crucial from the point of view of reducing the detrimental impact of the high blood on the patient's health status.

Q.2. The two main risk factors that are associated with the patient having a history of hypertension and high cholesterol. High blood pressure over the due course of time, leads to the weakening of the arteries. They are more vulnerable to have a clot or tend to burst more easily as well (Kjeldsen, 2018). The constant increase in the blood pressure usually leads to the arteries getting weakened over the due course of time. These arteries are, therefore, at a much higher risk of developing a stroke. Therefore, it is critical to managing normal blood pressure in order to reduce the chances of the patient getting another stroke.

The other underlying risk factor is the patient having high cholesterol levels. Cholesterol is usually not that easy to process in the body. This, however, can pile up in the major arteries of the body over the due course of time. The fat deposits that occur in the major arteries restrict the flow of blood (Pascoe, 2019). This fat also gets accumulated in the arterial lining making it thickened day by day. Due to this the conduction lowers and may lead to insufficiency in the same. This cholesterol gets deposited and leads to the formulation of atherosclerosis in the patient. This is another attributing risk factor for the patient to develop a stroke. This accumulation in the arterial passage also leads to the development of clot and with minor blood flow the clot can get dislodged and can get deposited in the major arteries. Eventually, leading to the development of ischemic stroke in the person.

Q.3. The main symptoms that are reflected in the given case study, as a result of his cerebral vascular accident are hemiplegia and dysphagia.

Hemiplegia is complete paralysis of the arms, legs, trunk especially of the same side of the body in which stroke has occurred. As the patient in the given case study is having a stroke on the left side, thus, his left part of the body can be observed to be paralyzed (Tani, 2018). The condition is also reflective of symptoms such as complete loss of the motor functions of the affected side of the body. It is often more severe than hemiparesis and there is no complete loss of activity in the given scenario. On occurrence the patient might experience the signs of difficultly in the walking pattern, holding things, increase in muscle stiffness, and muscle spasm as well. as the majority of the muscles are affected by the condition, the patient might also experience hurdles in minor activities such as speaking, smiling, swallowing food, and so on. Cerebrovascular accidents and transient ischemic attacks make up for the major causes to establish hemiplegia in the patient. Usually, during ischemic stroke, the brain is generally deprived of oxygen which results in the death of neurons (Sun, 2019). Another main reason is the injury caused to the corticospinal tract. It then affects the motor fibers in the tract which are responsible for providing signals for the movements of the body parts. Depending upon the site of the lesion the severity and extent of hemiplegia are described and observed in the patient. the motor fibers are also condensed in the internal capsule and a lesion to the same might also cause hemiplegia in the body.

Dysphagia is another major side effect that is seen in patients that suffer from a cerebrovascular accident. It is mainly characterized by difficulty in swallowing and is also extremely common in patients having a stroke. It can also lead to other life-threatening complications such as pneumonia and so on (Takizawa, 2016). Dysphagia can also bring about difficulty in eating, drinking, swallowing, and so on. Post any stroke there is an overall diminished motor control in the body. due to weakness in the body, there is an uncoordinated movement in the overall functioning. Stroke can leave a very negative impact on the functioning of the facial muscles as well and thus, impacting the overall balance of the muscle movement (Carnaby, 2018). In a stroke, if the swallowing muscles are not directly impacted, they might interfere with other motor functions that might impact the swallowing process, thus, leading to dysphagia in the patient. For example, if due to lack of muscle control the person is unable to sit up straight, he might not be able to swallow the food that efficiently as he might be able to, with intact muscle control.

Q.4. The patient has been prescribed multiple drugs for managing his condition. Some of the effective drugs prescribed to the patient are as follow:

1. Apixaban- It is the most common drug which is generally indicated for managing the risk of stroke and systemic embolism. The main action of the drug is to reduce the impact of the development of embolism which might lead to the development of stroke in the patient.

a. Pharmacodynamics- This drug selectively inhibits the factor Xa. It affects both the free and bound form of the compound, which is generally independent of the antithrombin III label. The drug also hinders the formation of prothrombinase. This helps in preventing the formation of thrombus in the person, who might be at risk of developing the same.

b. Pharmacokinetics- Half of the orally administered dose of the drug is excreted by the patient in an unchanged form. Whereas, the major 25% of the drug is expelled out in the form of O-dimethyl apixaban sulfate. Mostly 30% of all the forms in which this drug is administered, it is excreted out by the patient (Chang, 2016).

c. Adverse effects- Some of the adverse effects of this drug includes the following:

  1. Bleeding gums

  2. Headaches

  3. Chest pain or chest tightness

  4. Trouble in breathing

  5. Swelling in face or tongue

  6. Joints pain or swelling (mainly affecting the bogger joints of the body, such as the knee, shoulder and so on)

  7. Coughing or vomiting accompanied with blood in it.

  8. Having a dark-colored stool (Byon, 2017)

  9. Patient having a feeling of dizziness or faintness

d. Contraindications- The drug is contraindicated in multiple conditions as follow:

  1. If there is an increased risk of bleeding in the patient

  2. If the patient is having an artificial heart valve

  3. If there is a decrease in blood platelets count

  4. If the patient is having an eye surgery

  5. If the patient has been prescribed a local anesthesia

  6. If the patient is suffering from decreased kidney function

  7. A mother who is having a current feeding status.

2. Digoxin- It is one of the most recommended drugs for cardiovascular disease management. It is also a common drug for managing the condition of atrial fibrillation and for managing the symptoms of heart failure in an individual. It is generally administered in conjunction with diuretics.

a. Pharmacodynamics- The drug is mainly positive inotropic and negative chronotropic in nature. It helps in the regulation of the heart rate in the individual. This drug has been proven beneficial in reducing the associated cardiovascular risks and thus, helps in the reduction of fatality in the patient. This drug is also found to have a narrow therapeutic window (Patocka, 2020). The drug functions by limiting the action of the sodium pump and increases the levels of sodium and calcium in the body, causing a rapid increase in the contractibility of the heart muscles. It also acts through the parasympathetic nervous system and via the mode of the sinoatrial node, which brings about a decrease in the heart rate of the person.

b. Pharmacokinetics- This drug is absorbed by almost 70-80% in the first part of the small bowel. The bioavailability of the drug is, however, 50-90% as per the route of drug dose administered. If this drug is administered after a particular meal it might slow the process of absorption, but does not alters with the total amount of the drug absorbed in the body (Stopfer, 2016). If the patient is also taking any antibiotics, it might increase the absorption of digoxin, due to its elimination in the gut, which is not possible otherwise.

c. Adverse effects- Some of the common side effects of the drug are inclusive of the following:

  1. Nausea

  2. Vomiting

  3. Diarrhea

  4. Mental status alterations

  5. Dizziness

  6. Loss of appetite

  7. Arrhythmia

  8. Visual alterations

  9. Heart block

d. Contraindications- The commonly observed contraindications of the drug are as follow:

  1. Hypersensitivity to other drugs that might be based on digitalis glycosides.

  2. Patients that are having ventricular fibrillation

3. Simvastatin- This drug is mainly useful in lowering lipid levels. The drug is inclusive of the statin group of drugs, which helps in lowering the risk of cardiovascular disease in individuals. It is also a choice of drug for patients having diabetes mellitus, such as given in our case study. As this drug helps in lowering the lipid levels, it also safeguards a patient from developing other risk factors such as heart attack, atherosclerosis, peripheral artery disease, stroke, and so on (Van, 2017).

a. Pharmacodynamics- It is an oral drug that inhibits the HMG-CoA reductase. It acts by lowering the total cholesterol, low density, and high- density lipoprotein-cholesterol (Ostrowski, 2016). This mechanism is considered to be an effective source for reducing the risk of cardiovascular disease development. This hindrance to disease development also helps in lowering the other associated risk factors. Apart from reducing the risk factor, this drug also helps in enhancing the endothelial function and enhancing the stability of plaques formed in the patient. Thus, helping in reducing the oxidative stress and inflammation, which is the main underlying cause for inhibition of thrombogenic response in the patient.

b. Pharmacokinetics- The drug undergoes an extensive first pass in the liver itself. Oral administration of this drug is found to enhance the enzymatic activity of the drug, which is helpful in drug dissolution in the body. It is also helpful for maximizing the overall effects of the drug on the patient. Genetic dissimilarity in the OATP1B1 hepatic transporter encoded by the SCLCO1B1 gene has been found to have a direct impact on the pharmacokinetics of this drug (Wu, 2017). Patients having these genotypes are provided with a dosage of 20mg of simvastatin in order to avert any adverse drug reaction to the patient.

c. Adverse effects- There is some major and minor serious adverse effect of this drug on the patients. The minor side effects are inclusive of headache, nausea, stomach pain, joint pain, and so on. Some of the harmful side effects are inclusive of the following:

  1. Muscle breakdown, also commonly known as rhabdomyolysis (Coste, 2019).

  2. Kidney failure

  3. Jaundice

  4. Liver toxicity

  5. Muscle spasm

  6. Diarrhea

  7. Severe anemia

  8. Severe muscle pain and weakness

  9. Severe swelling in extremities

  10. Severe and constant stomach ache.

d. Contraindication- Some of the common conditions where this drug is contraindicated are as follow:

  1. Patients that are prone to alcoholism

  2. In case of any recent operation

  3. Patient having metabolic syndrome

  4. In the case of pregnant women

  5. Females who are actively breastfeeding

  6. Patient having any kind of liver-related issues

  7. Immune-mediated necrotizing myopathy

  8. In case of a patient having a memory loss

Q.5. The first-pass effect is also commonly known as first-pass metabolism or presystemic metabolism. It mainly concentrates on the concept of drug metabolism where the drug concentration is hugely reduced before it reaches the systemic circulation (Nikoubashman, 2019). It also helps in identifying the fraction of the drug that is lost during the mechanism of absorption, which mainly occurs in the liver or gut part of the body. after the drug is administered orally to the patient, it is absorbed in the digestive system and then enters the hepatic portal system. It is then carried through the means of the portal vein into the liver before it reaches the rest of the parts of the body. The drugs are generally filtered in the liver to regularize the required dose of the drug to the patient, as required by them. This is also helpful in reducing the overall load on the circulatory system of the body. The first pass of the drug is important to help in reducing the bioavailability of the drug.

Four main parts systems affect the first pass regulation of any drug. These systems are enzymes present in the gut wall, bacterial enzymes, hepatic enzymes, and enzymes present in the gastrointestinal lumen (Peters, 2016). The other drug administration routes, do not oblige with the concept of the first pass and are directly absorbed in the body, without being metabolized. Oral bioavailability on the other hand, especially for certain vulnerable drugs can increase the complications associated with liver functions and might compromise with the normal functioning of the same (Zhao, 2019). Therefore, the first pass plays a crucial role in altering the bioavailability of the drug and maximizing its mechanism of action post-administration to the patient.

References

Byon, W., Sweeney, K., Frost, C., & Boyd, R. A. (2017). Population pharmacokinetics, pharmacodynamics, and exploratory exposure–response analyses of apixaban in subjects treated for venous thromboembolism. CPT: Pharmacometrics & Systems Pharmacology, 6(5), 340-349. https://doi.org/10.1002/psp4.12184

Carnaby, G., Sia, I., & Crary, M. (2019). Associations between spontaneous swallowing frequency at admission, dysphagia, and stroke-related outcomes in acute care. Archives of Physical Medicine and Rehabilitation, 100(7), 1283-1288. https://doi.org/10.1016/j.apmr.2019.01.009

Chang, M., Yu, Z., Shenker, A., Wang, J., Pursley, J., Byon, W., ... & Frost, C. E. (2016). Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. The Journal of Clinical Pharmacology, 56(5), 637-645. https://doi.org/10.1002/jcph.633

Coste, J., Billionnet, C., Rudnichi, A., Pouchot, J., Dray-Spira, R., Giral, P., & Zureik, M. (2019). Statins for primary prevention and rhabdomyolysis: A nationwide cohort study in France. European Journal of Preventive Cardiology, 26(5), 512-521. https://doi.org/10.1177%2F2047487318776831

Hermida, R. C., Ayala, D. E., Smolensky, M. H., Fernández, J. R., Mojón, A., & Portaluppi, F. (2016). Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks. Hypertension Research, 39(5), 277-292. https://doi.org/10.1038/hr.2015.142

https://doi.org/10.1161/119.025148

Kjeldsen, S. E. (2018). Hypertension and cardiovascular risk: General aspects. Pharmacological Research, 129, 95-99. https://doi.org/10.1016/j.phrs.2017.11.003

Nikoubashman, O., Dekeyzer, S., Riabikin, A., Keulers, A., Reich, A., Mpotsaris, A., & Wiesmann, M. (2019). True first-pass effect: first-pass complete reperfusion improves clinical outcome in thrombectomy stroke patients. Stroke, 50(8), 2140-2146.

O'Neal, W. T., Kamel, H., Zhang, Z. M., Chen, L. Y., Alonso, A., & Soliman, E. Z. (2016). Advanced interatrial block and ischemic stroke: The Atherosclerosis Risk in

Communities Study. Neurology, 87(4), 352-356. https://doi.org/10.1212/WNL.0000000000002888

Ostrowski, S. M., Johnson, K., Siefert, M., Shank, S., Sironi, L., Wolozin, B., ... & Ziady, A. G. (2016). Simvastatin inhibits protein isoprenylation in the brain. Neuroscience, 329, 264-274. https://doi.org/10.1016/j.neuroscience.2016.04.053

Pascoe, M., Ski, C. F., Thompson, D. R., & Linden, T. (2019). Serum cholesterol, body mass index and smoking status do not predict long-term cognitive impairment in elderly stroke patients. Journal of the Neurological Sciences, 406, 116-476. https://doi.org/10.1016/j.jns.2019.116476

Patocka, J., Nepovimova, E., Wu, W., & Kuca, K. (2020). Digoxin: Pharmacology and Toxicology-A Review. Environmental Toxicology and Pharmacology, 103-400. https://doi.org/10.1016/j.etap.2020.103400

Peters, S. A., Jones, C. R., Ungell, A. L., & Hatley, O. J. (2016). Predicting drug extraction in the human gut wall: assessing contributions from drug metabolizing enzymes and transporter proteins using preclinical models. Clinical Pharmacokinetics, 55(6), 673-696. https://doi.org/10.1007/s40262-015-0351-6

Stopfer, P., Giessmann, T., Hohl, K., Sharma, A., Ishiguro, N., Taub, M. E., ... & Müller, F. (2016). Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin, and rosuvastatin. Clinical Pharmacology & Therapeutics, 100(3), 259-267. https://doi.org/10.1002/cpt.406

Sun, J., & Yue, F. (2019). Suppression of REDD1 attenuates oxygen glucose deprivation/reoxygenation‐evoked ischemic injury in neuron by suppressing mTOR‐mediated excessive autophagy. Journal of Cellular Biochemistry, 120(9), 14771-14779. https://doi.org/10.1002/jcb.28737

Takizawa, C., Gemmell, E., Kenworthy, J., & Speyer, R. (2016). A systematic review of the prevalence of oropharyngeal dysphagia in stroke, Parkinson’s disease, Alzheimer’s disease, head injury, and pneumonia. Dysphagia, 31(3), 434-441. https://doi.org/10.1007/s12975-018-0625-z

Tani, M., Ono, Y., Matsubara, M., Ohmatsu, S., Yukawa, Y., Kohno, M., & Tominaga, T. (2018). Action observation facilitates motor cortical activity in patients with stroke and hemiplegia. Neuroscience Research, 133, 7-14. https://doi.org/10.1016/j.neures.2017.10.002

Van Diemen, M. P., Berends, C. L., Akram, N., Wezel, J., Teeuwisse, W. M., Mik, B. G., ... & Groeneveld, G. J. (2017). Validation of a pharmacological model for mitochondrial dysfunction in healthy subjects using simvastatin: a randomized placebo-controlled proof-of-pharmacology study. European Journal of Pharmacology, 815, 290-297. https://doi.org/10.1016/j.ejphar.2017.09.031

Weiss, A., Beloosesky, Y., Kenett, R. S., & Grossman, E. (2016). Change in systolic blood pressure during a stroke, functional status, and long-term mortality in an elderly population. American Journal of Hypertension, 29(4), 432-438. https://doi.org/10.1093/ajh/hpv118

Wu, H. F., Hristeva, N., Chang, J., Liang, X., Li, R., Frassetto, L., & Benet, L. Z. (2017). Rosuvastatin pharmacokinetics in Asian and white subjects wild type for both OATP1B1 and BCRP under control and inhibited conditions. Journal of Pharmaceutical Sciences, 106(9), 2751-2757. https://doi.org/10.1016/j.xphs.2017.03.027

Zhao, C., Ying, Z., Hao, D., Zhang, W., Ying, X., & Yang, G. (2019). Investigating the bioavailabilities of olerciamide A via the rat's hepatic, gastric and intestinal first‐pass effect models. Biopharmaceutics & Drug Disposition, 40(3-4), 112-120. https://doi.org/10.1002/bdd.2175

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