PHARMACOKINETICS AND PHARMACODYNAMICS NURS 6521

PHARMACOKINETICS AND PHARMACODYNAMICS NURS 6521

PHARMACOKINETICS AND PHARMACODYNAMICS NURS 6521

Pharmacokinetics involves sequential processes, including absorption, distribution, metabolism, and excretion that occur in the body following drug administration (Arcangelo & Peterson, 2018). On the other hand, pharmacodynamics is the effect of a particular drug on the body. It includes side effects, physiological processes, and drug reactions. Unique patient features, including sex, age, and health condition, influence the two processes. My focus for this discussion purpose from my experience will be a 48-year-old male with diabetes mellitus Type 2.

Scenario: 48-year-old male with diabetes type 2 who was diagnosed with diabetes since the age of 20 but recently started going into diabetic ketoacidosis frequently. Patients presents with blood glucose of 690. Patient takes multiple medications including Lyrica, Metformin, Atorvastatin, and Lisinopril for hypertension, renal disease, gout, coronary artery disease, and neuropathy. I do not recall all the medications he was on.

Due to the complications of diabetes, these patients are usually prone to cardiovascular diseases, stroke, kidney diseases, vision alterations, among other diseases. Therefore, these patients are usually on many other drugs apart from the ones specified for diabetes mellitus.

 

Factors affecting pharmacokinetics

Liver metabolizes many drugs but with diabetic there is a decreased CYP 3A4 which is hepatic enzymatic activity and protein levels due to taking other medications for other complications brought about by diabetes (Uehara et al 2017). More often, these patients also experience an increase in glomerular infiltration rate causing excretion concerns related to micro vascular and macro vascular changes and renal function loss (Trevisan & Dodesini, 2017). There is also the effect of distribution due to the process of glycation where albumin has decreased affinity for some fatty acids decreasing efficiency of fatty acid grafted drugs (Gajahi Soudahome et al., 2018). Due to the different drugs that this patient was taking, there was the effect of decreased membrane permeability influenced by insulin induced capillary perfusion affecting absorption (McConell et al., 2020)

 

Pharmacodynamics

Metformin activates the enzyme adenosine monophosphate kinase (AMPK) which inhibits enzymes involved in gluconeogenesis and glycogen synthesis in the liver blocking the enzyme pyruvate carboxylase, while stimulating insulin signaling and glucose transport in muscles (Hunter et al., 2018). By blocking this enzyme, lactic acid accumulates causing lactic acidosis. This could happen with high doses of metformin or with patient with decreased renal clearance. This patient takes Lisinopril, ACE inhibitor, which lowers blood pressure by inhibiting the enzymes Angiotensin I and II which constricts blood vessels. Renal function can be decreased with chronic use of ACE inhibitors thus renal dosing is highly advised.

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Personalized Care

This patient was seeing different doctors for diabetes, renal disease, and hypertension. Her medications were not revised by these providers hence the complications due to polypharmacy. For her personalized care, I would recommend her medications to be revised by the providers, a goal placed to focus on decreasing A1C, avoiding sedentary lifestyle including diet change, at home glycemic control, improved physical activity, and regular follow ups.

References

Uehara, S., Uno, Y., Nakanishi, K., Ishii, S., Inoue, T., Sasaki, E., & Yamazaki, H. (2017). Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone. Drug Metabolism and Disposition, 45(5), 457–467. https://doi.org/10.1124/dmd.116.074898

McConell, G. K., Sjøberg, K. A., Ceutz, F., Gliemann, L., Nyberg, M., Hellsten, Y., Frøsig, C., Kiens, B., Wojtaszewski, J. F. P., & Richter, E. A. (2020). Insulin‐induced membrane permeability to glucose in human muscles at rest and following exercise. The Journal of Physiology, 598(2), 303–315. https://doi.org/10.1113/jp278600

Trevisan, R., & Dodesini, A. R. (2017). The Hyperfiltering Kidney in Diabetes. Nephron, 136(4), 277–280. https://doi.org/10.1159/000448183

Gajahi Soudahome, A., Catan, A., Giraud, P., Assouan Kouao, S., Guerin-Dubourg, A., Debussche, X., le Moullec, N., Bourdon, E., Bravo, S. B., Paradela-Dobarro, B., Álvarez, E., Meilhac, O., Rondeau, P., & Couprie, J. (2018). Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide. Journal of Biological Chemistry, 293(13), 4778–4791. https://doi.org/10.1074/jbc.m117.815274

Hunter, R. W., Hughey, C. C., Lantier, L., Sundelin, E. I., Peggie, M., Zeqiraj, E., Sicheri, F., Jessen, N., Wasserman, D. H., & Sakamoto, K. (2018). Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase. Nature Medicine, 24(9), 1395–1406. https://doi.org/10.1038/s41591-018

In March 2020 Arkansas began to see the first surge of patients with coronavirus (COVID-19). In the beginning, treatment for the virus was based on oxygen saturation, and symptom management. By August 2021 monoclonal antibodies, Regen-Cov, casirivimab and imdevimab given together became the treatment of choice for the Delta strain of the virus under Emergency Use Authorization by the Food and Drug Administration (FDA.gov).

A 50 y/o male patient with moderate obesity and high blood pressure presented with cough, tachypnea and fever. He reported onset of symptoms eight days prior to seeking treatment and tested positive for COVID-19 using a rapid antigen test. His temperature was 102 degrees, heart rate 124, BP (Blood Pressure) 147/92 and oxygen saturation was 87%. The patient had no known drug allergies. He did not meet inclusion criteria due to his oxygen saturation but after doing some deep breathing, coughing, and sitting upright rather than lying down his oxygen saturation increased to 94% and remained there. The decision was made to give him Regen-COV. The patient was not vaccinated against COVID-19.

Individualized Plan of Care

Regen-COV 1200mg (casirivimab 600mg and imdevimab 600mg) was given subcutaneously using four injection sites and administering 2.5 ml per site. The patient was asked to remain in a supine position for 10 minutes post injection to decrease the amount of irritation to the injection sites. He was monitored for one hour post injection with no change in vital signs or evidence of any adverse reaction to treatment. The patient was sent home with his wife, an oxygen saturation monitor and educational materials. He was instructed to do his deep breathing exercises every hour while awake.

The following afternoon I called the patient to reassess. He reported that his fever was resolving and had been no higher than 100 degrees since that morning. He reported feeling weak but not short of breath. His oxygen saturation was 94%. He felt like he was improving.

The patient was also called 48 hours after receiving monoclonal antibody treatment and reported, ¨I am sure you saved my life with that medicine. ¨ He was afebrile, and his oxygen saturation was 97%. He reported fatigue but his malaise was resolved. He reported no irritation at the injection sites and was instructed to follow up with his physician if his symptoms returned or worsened. I spoke to him one week post injection and he reported a full recovery and returned to work.

 

Pharmacokinetics

Pharmacokinetics explain what the body does to the drug in terms of absorption, distribution, metabolism and excretion. (Rosenthal and Burchum, 2018). Regen-Cov is lab-created human antibodies given in combination (Food and Drug Administration, 2021).

Regen-COV has a half-life of 26-30 days and is degraded into small peptides and amino acids in the body. It is not metabolized by the liver or kidneys. Because of this, patient weight, hepatic or renal impairment do not affect exposure of the drug or require dose modification. It is also very unlikely that Regen-COV will interact with other medications (Deeks, 2021).

Pharmacodynamics

Pharmacodynamics is the study of the effects of the drug on the body and how the effects are produced (Rosenthal and Burchum, 2018. pp 22-23). Regen-COV antibodies have a high affinity for the spike protein of the COVID-19 virus. The antibody binds to the spike protein and prevents the virus from binding to human cells. This reduces the viral replication in the lungs and other body tissues (Deeks, 2021).

 

References 

Deeks, E.D. (2021, October 30). Casirivimab/Imdevimab: First Approval. Nature Public Health Emergency Collection, 81(17), 2047-2055. doi:10.1007/s40265-021-01620-z.

Food and Drug Administration. (2021). U.S. Food & Drug Administration. Retrieved from FDA.gov:

FDA.gov/drugs/drug-safety-and-availability/fda-authorizes-regen-cov-monoclonal-antibody-

Therapy.

 

Rosenthal, L.D., & Burchum, J.R. (2021). Lehneś Pharmacotherapeutics for Advanced Practice Nurses

And Physician Assistants. St. Louis: Elsevier.

Top of Form

Hello Tracey,

 

Thank you for sharing your experience.  As I start this class, I want to learn more about the subjects at-hand, so I paid attention and further researched some points of discussion from your writing to increase my knowledge.  Two points of your discussion that I further researched to help me understand the information is about the drug’s no effect of liver and kidney and the half-life of the drug.  You talked about Regen-Cov not being metabolized by the liver or kidneys and that it was administered subcutaneously.  Subcutaneous injections are absorbed by the fatty tissue with less blood vessels under the skin and metabolized into the circulatory system after reaching the blood vessels (Kim, Park, & Lee, 2017).  This tissue/blood vessel absorption and direct circulatory system metabolizes explains the lack of use of the liver and kidney.  Next, you mentioned about half-life of Regen-Cov.  Medication half-life has significant implications for dosing regimen and peak-to-trough ratio at the balanced state (Smith, Beaumont, Maurer, & Di, 2017).  After understanding the importance of half-life, I can relate the information to the use of the drug with the patient.  Moving forward, I look forward to learning more about pharmacokentics and pharmacodynamics of medications and how they are implemented into treatment.  Thank you, again.

 

References

 

Kim, H., Park, H., & Lee, S. J. (2017). Effective method for drug injection into subcutaneous tissue. Scientific reports7(1), 1-11.

 

Smith, D. A., Beaumont, K., Maurer, T. S., & Di, L. (2017). Relevance of half-life in drug design: Miniperspective. Journal of medicinal chemistry61(10), 4273-4282.

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