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

Week 1 Discussion Post Tracey Sanchez

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.

Pharmacokinetics and Pharmacodynamics

            When prescribing medication, it is crucial to consider several individual patient factors that might affect the pharmacokinetic and pharmacodynamic process (Reeve et al., 2017). For instance, while working with the geriatric population, I encountered an 85-year-old female patient with a history of atrial fibrillation and serum creatine of 1.8mg/dl. The patient was prescribed digoxin to help manage the rapid heart rate. A maintenance dose of 125mcg tabs once a day was decided based on the patient’s pharmacodynamic and pharmacokinetic processes.

Advanced age is characterized by reduced functionality of several regular body processes responsible for functional integration between different cells and organs. The 85-year-old patient displayed several pharmacokinetic changes, with the main ones being a reduction in hepatic and renal clearance and decreased distribution volume of water-soluble drugs leading to higher serum levels (Drenth‐van Maanen et al., 2019). Consequently, some of the pharmacokinetic changes associated with the patient’s advanced age include increased sensitivity to drugs like digoxin.

Serum creatine of 1.8mg/dl is quite high indicating that the patient’s kidneys are not functioning properly. However, since approximately 67% of digoxin undergoes renal clearance, it was necessary to calculate the standard renal clearance of the drug, which is 6 liters per hour per 70 kg body weight, with a creatinine clearance of 100 mL/min (Holford, 2017). The patient’s creatinine clearance is however reduced hence the need to administer a lower dose of the drug. A once-daily dosing frequency is thus recommended with a bioavailability of 0.7 that requires 127 mcg/day as the daily maintenance dose. The dose should however be monitored closely for further changes.

 

 

References

Drenth‐van Maanen, A. C., Wilting, I., & Jansen, P. A. F. (2019). Prescribing medicines to older people—How to consider the impact of aging on human organ and body functions. British Journal of Clinical Pharmacology, 86(10), 1921–1930. https://doi.org/10.1111/bcp.14094

Holford N.G. (2017). Pharmacokinetics & pharmacodynamics: rational dosing & the time course of drug action. Katzung B.G.(Ed.), Basic & Clinical Pharmacology, 14e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2249&sectionid=175215748

Reeve, E., Trenaman, S. C., Rockwood, K., & Hilmer, S. N. (2017). Pharmacokinetic and pharmacodynamic alterations in older people with dementia. Expert Opinion on Drug Metabolism & Toxicology, 13(6), 651–668. https://doi.org/10.1080/17425255.2017.1325873

Case of a dialysis patient who has atrial fibrillation, irregular rhythm, increased heart rate, and CHF. Patient has been fluid overload, no leg edema but with crackles on both lungs.  Hemoglobin and hematocrit level are within normal limits. She went to the hospital for SOB. Initial treatment was dialysis to relieve SOB. Orders were Amiodarone IV drip, and oxygen.

Atrial fibrillation (AF) is a dangerous heart condition where there is an irregular and rapid heart rate. The heart beats out of coordination with the ventricles. People with AF have a four to fivefold increased risk of stroke and a two to threefold increased risk of heart failure (McCance, & Huether, 2019).

Amiodarone, a potent antiarrhythmic medication is used in treatment of irregular heart rate, such as atrial fibrillation, supraventricular and ventricular tachyarrhythmia. It is used to restore normal heart rhythm and maintain regular heart rate. This medication stays in the body for weeks to months, even after taking it.

Pharmacokinetics of Amiodarone

Pharmacokinetics is divided into four phases which are absorption, distribution, metabolism and excretion. Amiodarone has oral and IV medications. Oral amiodarone has a slow and variable absorption of about 40 % in the body. IV Amiodarone begins to act within one hour, with rapid onset of action within minutes after an infusion. The bioavailability may be influenced by age, liver disease, and interactions with other drugs or substances that inhibit or induce cytochrome (CYP) 450, thus affecting efficacy) (Biancatelli, et al, 2019). Amiodarone is a lipophilic drug, which absorption is enhanced if taken with foods high in fat content, and has a large but variable volume distribution (66 L/kg of body weight) (Biancatelli, et al, 2019).My patient weighs 70 kg and there is good volume distribution of the medication. She is below 65, so there is less likely of a adverse effects due to age. There is no information as to gender issue problems with Amiodarone.

Pharmacodynamics

She was given an IV dose of Amniodarone and according to hospital report she converted from atrial fibrillation to normal sinus rhythm. Pharmacodynamics is the study of the biochemical and physiologic effects of drugs on the body and the molecular mechanism by which those effects are produced (Rosenthal, & Burchum, 2021).

The short half-life for disappearance of amiodarone from plasma after intravenous administration is likely a measure of drug redistribution from vascular space into tissue and not body elimination.  Amiodarone is metabolized by eliminated by hepatic metabolism and biliary excretion, so it is very beneficial for my patient. About less than 1% of the dose is excreted unchanged in the urine. Biliary excretion may have a role in the overall elimination of the drug

Evidence from literature suggests that dronedarone (amiodarone derived) causes a specific partial inhibition of tubular organic cation transporters leading to a limited increase in serum creatinine not related with a decline in renal function (Conti, et al, 2015).

 

References

Conti, V., Biagi, C., Melis, M., Fortino, I., Donati, M., Vaccheri, A., Venegoni, M., Motola, D.    (2015). Acute renal failure in patients treated with dronedarone or amiodarone: a large population-based cohort study in Italy. European Journal of Clinical Pharmacology, Vol. 71(9). ISSN: 0031-6970. DOI 10.1007/s00228-015-1903-2

Biancatelli, R.M., Congedo, V., Calvosa, L., Ciacciarelli, M., Polidoro, A., Iuliano, L. Adverse reactions of Amniodarone. Journal of geriatric cardiology, (JGC) Vol. 16 (7) ISSN: 1671-5411. doi: 10.11909/j.issn.1671-5411.2019.07.004

McCance, K.L. and Huether, S.E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St. Louis, MO: Mosby Elsevier.

Rosenthal, L.D., and Burchum, J.R., 2021. Lehne’s pharmacotherapeutics for advanced practice nurses and physicians assistants (2nd ed.) St. Louis, MO: Elsevier

Grading Rubric

Performance Category	100% or highest level of performance 100% 16 points	Very good or high level of performance 88% 14 points	Acceptable level of performance 81% 13 points	Inadequate demonstration of expectations 68% 11 points	Deficient level of performance 56% 9 points	Failing level of performance 55% or less 0 points
Total Points Possible= 50	16 Points	14 Points	13 Points	11 Points	9 Points	0 Points
Scholarliness Demonstrates achievement of scholarly inquiry for professional and academic topics.	Presentation of information was exceptional and included all of the following elements: Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information.	Presentation of information was good, but was superficial in places and included all of the following elements: Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information.	Presentation of information was minimally demonstrated in all of the following elements: Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information.	Presentation of information is unsatisfactory in one of the following elements: Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information.	Presentation of information is unsatisfactory in two of the following elements: Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information.	Presentation of information is unsatisfactory in three or more of the following elements Provides evidence of scholarly inquiry relevant to required TD topic(s). Presents specific information from scholarly sources to develop a comprehensive presentation of facts. Uses at least one outside scholarly reference that is relevant, less than 5 years old (use of older references requires instructor permission) and reliable for the required topic.* Uses in-text citation and full reference at end of posting when presenting another person’s thoughts as quotes or paraphrase of information
	16 Points	14 Points	13 Points	11 Points	9 Points	0 Points
Application of Course Knowledge Demonstrate the ability to analyze and apply principles, knowledge and information learned in the outside readings and relate them to real-life professional situations	Presentation of information was exceptional and included all of the following elements: Applies principles, knowledge and information from scholarly resources to the required topic. Applies facts, principles or concepts learned from scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.	Presentation of information was good, but was superficial in places and included all of the following elements: Applies principles, knowledge and information from scholarly resources to the required topic. Applies facts, principles or concepts learned from scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.	Presentation of information was minimally demonstrated in the all of the following elements: Applies principles, knowledge and information from scholarly resources to the required topic. Applies facts, principles or concepts learned from scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.	Presentation of information is unsatisfactory in one of the following elements: Applies principles, knowledge and information from scholarly resources to the required topic. Applies facts, principles or concepts learned from and scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.	Presentation of information is unsatisfactory in two of the following elements: Applies principles, knowledge and information from scholarly resources to the required topic. Applies facts, principles or concepts learned from scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.	Presentation of information is unsatisfactory in three of the following elements Applies principles, knowledge and information and scholarly resources to the required topic. Applies facts, principles or concepts learned scholarly resources to a professional experience. Application of information is comprehensive and specific to the required topic.
	10 Points	9 Points			6 Points	0 Points
Interactive Dialogue Initial post should be a minimum of 300 words (references do not count toward word count) The peer and instructor responses must be a minimum of 150 words each (references do not count toward word count) Responses are substantive and relate to the topic.	Demonstrated all of the following: Initial post must be a minimum of 300 words. The peer and instructor responses must be a minimum of 150 words each. Responses are substantive Responses are related to the topic of discussion.	Demonstrated 3 of the following: Initial post must be a minimum of 300 words. The peer and instructor responses must be a minimum of 150 words each. Responses are substantive Responses are related to the topic of discussion.			Demonstrated 2 of the following: Initial post must be a minimum of 300 words. The peer and instructor responses must be a minimum of 150 words each. Responses are substantive Responses are related to the topic of discussion.	Demonstrated 1 or less of the following: Initial post must be a minimum of 300 words. The peer and instructor responses must be a minimum of 150 words each. Responses are substantive Responses are related to the topic of discussion.
	8 Points	7 Points	6 Points	5 Points	4 Points	0 Points
Grammar, Syntax, APA Points deducted for improper grammar, syntax and APA style of writing. The source of information is the APA Manual 6th Edition Error is defined to be a unique APA error. Same type of error is only counted as one error.	The following was present: 0-3 errors in APA format AND Responses have 0-3 grammatical, spelling or punctuation errors AND Writing style is generally clear, focused on topic,and facilitates communication.	The following was present: 4-6 errors in APA format. AND/OR Responses have 4-5 grammatical, spelling or punctuation errors AND/OR Writing style is somewhat focused on topic.	The following was present: 7-9 errors in APA format. AND/OR Responses have 6-7 grammatical, spelling or punctuation errors AND/OR Writing style is slightly focused on topic making discussion difficult to understand.	The following was present: 10- 12 errors in APA format AND/OR Responses have 8-9 grammatical, spelling and punctuation errors AND/OR Writing style is not focused on topic, making discussion difficult to understand.	The following was present: 13 – 15 errors in APA format AND/OR Responses have 8-10 grammatical, spelling or punctuation errors AND/OR Writing style is not focused on topic, making discussion difficult to understand. AND/OR The student continues to make repeated mistakes in any of the above areas after written correction by the instructor.	The following was present: 16 to greater errors in APA format. AND/OR Responses have more than 10 grammatical, spelling or punctuation errors. AND/OR Writing style does not facilitate communication
	0 Points Deducted					5 Points Lost
Participation Requirements	Demonstrated the following: Initial, peer, and faculty postings were made on 3 separate days					Failed to demonstrate the following: Initial, peer, and faculty postings were made on 3 separate days
	0 Points Lost					5 Points Lost
Due Date Requirements	Demonstrated all of the following: The initial posting to the graded threaded discussion topic is posted within the course no later than Wednesday, 11:59 pm MT. A minimum of one peer and one instructor responses are to be posted within the course no later than Sunday, 11:59 pm MT.					Demonstrates one or less of the following. The initial posting to the graded threaded discussion topic is posted within the course no later than Wednesday, 11:59 pm MT. A minimum of one peer and one instructor responses are to be posted within the course no later than Sunday, 11:59 pm MT.