Feb 23, 2024 Discussion: Pharmacokinetics and Pharmacodynamics
Discussion Pharmacokinetics and Pharmacodynamics
A sample Answer For the Assignment: Discussion: Pharmacokinetics and Pharmacodynamics
Misoprostol is a drug used for two different types of labor and delivery situations. It can be used to induce labor by softening the cervix and initiating contractions. It can also be used as a uterotonic during a postpartum hemorrhage. I worked as a labor and delivery nurse at a Trauma 1 center in Irvine, California, for many years. During that time, I witnessed many high-risk patients hemorrhage after delivering. In this event, it is crucial that the healthcare team acts fast and provides the patient with the necessary drugs to contract the uterus and stop the bleeding.
However, it is essential to consider the patient’s vitals and medical history when deciding which uterotonic to use. Some uterotonics are contraindicated in patients with asthma or hypertension. Although other uterotonics have a faster absorption rate and longer duration, Misoprostol is safe for hypertensive or asthma patients. Misoprostol can be given vaginally, rectally, sub-lingual, or buccal. One study compared the effects of the drug when given rectally versus sub-lingual and found that intra-operative bleeding and postpartum hemorrhaging during a cesarian delivery were lower when given sub-lingual (Sweed et al., 2018). This is because the administration route affects the absorption and distribution rate. I was caring for a woman who had complications during the placenta delivery. I was working at a teaching hospital where residents worked as physicians on the unit. The resident decided to administer Misoprostol vaginally. The woman continued to hemorrhage despite the residents’ efforts. This was because of the route of administration. The Misoprostol could not be absorbed and cross the cell membrane because of the amount of blood coming out of her vagina.
Therefore, the plasma drug concentration could not reach a level high enough to be therapeutic. Because the patient was only 25 and in good medical condition, age did not affect the effectiveness of the medication. Infants and the elderly are at risk because of decreased drug-metabolizing capacity and kidney function (Rosenthal et al., 2021). In this scenario, the baby was unaffected because the umbilical cord had been cut and no longer shared blood with its mother. The patient’s personalized plan of care would be to change the route of administration to sub-lingual. The drug would be able to take full effect by absorbing into the blood, where it will stimulate uterine contractions, which will help stop the bleeding. Misoprostol acts as a prostaglandin that binds to the smooth muscle cells in the uterine lining and causes the uterus to contract. A common side effect of the drug is abdominal pain and diarrhea. This is due to the byproduct misoprostolic acid released during the drug’s metabolism at its peak plasma concentration (Krugh & Maani, 2022). Because diarrhea is a common side effect, I would increase the patient’s fluids to ensure she does not become dehydrated or hypovolemic.
Discussion Pharmacokinetics and Pharmacodynamics
References
Krugh, M., Maani, C. (2022). Misoprostol. In StatPearls. StatPearls Publishing.
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Rosenthal, L. D., Burchum, J. R., & Rosenthal, L. D. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants. Elsevier.
Sweed, M. S., El-Saied, M. M., Abou-Gamrah, A. E., El-Sabaa, H. A., Abdel-Hamid, M. M., Hemeda, H., Mansour, A. M., Shawky, M. E., El-Sayed, M. A., & Mohamed, R. M. (2018). Rectal vs. sublingual misoprostol before cesarean section: double-blind, three-arm, randomized clinical trial. Archives of Gynecology & Obstetrics, 298(6), 1115–1122. https://doi.org/10.1007/s00404-018-4894-2
Introduction
The processes that a medicine goes through in the body after administration are referred to as pharmacokinetics. Absorption, distribution, metabolism, and excretion are all included in this. Pharmacodynamics, on the other hand, deals with the effects that drugs have on the body, such as adverse effects. Variables like a patient’s genetics, gender, ethnicity, age, behavioral factors, medical history, and concurrent drugs all have an impact on pharmacokinetics and pharmacodynamics. According to the case study, these variables especially age do indeed change the drugs pharmacokinetics and pharmacodynamics (Rosenthal. & Burchum, 2018).
Age influencing pharmacodynamics and pharmacokinetics
The patient is of advanced age whereby it has been stated that they are 74 years old this is indeed can affect the pharmacodynamics and pharmacokinetics related to the drug. In advanced age you find the boy’s physiology has changed thus affecting the pharmacokinetics and elements such as absorption, distribution, metabolism and excretion. One of the most significant impacts in old age is whereby you’ll have a decreased glomeruli filtration rate which determines the level of drug elimination. Since it is decreased it could lead to the drug being retained in the system and leading to toxicity (Sieder et al., 2016).
In old age there is also decreased gastrointestinal motility thus leading to delayed absorption rate. This leads to delayed onset of pharmacological effects of drugs thus making them less effective. The peak drug concentrations are also affected hence the drug doesn’t reach its maximum capacity for effect (Mangoni & Jarmuzewska, 2019).
Age also increases the body fat which could lead to increase the volume of distribution increases. Therefore if the drug has to be distributed to a wider area than affection it will affect its expected performance thus not delivering the desired therapeutic effect. Due to the increased body fat there is also decreased body water levels thus leading to the drug’s elimination half-lives also getting increased (Sieder et al., 2016).
Having an advanced age also affects metabolism which mostly occurs in the liver. This occurs in due to the decreased required enzymes that may no longer be available due to the physiological changes that occur because of age. This also leads to decreased clearance hence the already metabolised drug aren’t cleared from the system (Mangoni & Jarmuzewska, 2019).
Age impacting pharmacodynamics occurs through decrease in effect for beta-adrenergic agents. This is due to decrease in response in the vascular, cardiac, and pulmonary tissues due to a decline in some required proteins. There is also reduced sensitivity to drugs due to the body’s receptors undergoing physiological changes. Therefore if the response and sensitivity is inhibited the desired therapeutic effect isn’t achieved.
Homeostatic mechanisms are also seen to influence the pharmacodynamics in that in advanced age it is reduced. The mechanisms are seen to reduce in old age. Therefore in the case the drugs lead to adverse effects the body takes a longer period of time to return to the initial state (Sieder et al., 2016).
Changes in the Process that Impact the Patient’s Recommended Drug Therapy
Due to the old age the pharmacodynamics and pharmacokinetics has been impacted. The absorption has been delayed due to decreased gastric motility, on the distribution end the volume of distribution has increased due to the increased body fat and the metabolism due to decreased enzymes has also decreased.
The physiological changes in the glomeruli has decreased the glomeruli filtration rate hence decreasing excretion and could lead to toxicity. The pharmacodynamics due to decrease in sensitivity, decrease in response and reduced homeostatic mechanisms negatively affect it (Mancia et al., 2014).
Therefore encompassing all this there is a definite change in the recommended drug therapy in order to benefit the patient. The changes are in medication such as atenolol will be used in place of the beta-blocker metoprolol, starting at 25 to 200 mg per day. However, fast response is attainable with longer release modules and can be delivered thrice daily, thus it’s advised to begin new medication, notably such as beta-blockers, with prolonged release formulae.
Instead of ibuprofen that is contraindicated with warfarin patients should be prescribed acetaminophen orally 500mg thrice daily to manage the pain. I would also advise using lipid-lowering drugs other than statins to lower the low-density lipoprotein cholesterol levels (Mangoni & Jarmuzewska, 2019).
How to Improve the Drug Therapy Plan
Patients with a high risk of cardiovascular disease, a heart attack, or is known diabetic, such as this patient, are advised to begin taking a moderate-intensity statin with the aim of reducing LDL-C levels by 30% or more. For this patient, it is advised to utilize Ezetimibe, administered orally at a dose of 10 mg each day. Cardiovascular diseases, diabetes mellitus, left ventricular dysfunction and diabetic neuropathy can receive treatment by use of angiotensin converting enzyme inhibitors.
They can also be used to prevent strokes. Starting doses of ramipril range from 1.25 mg to 2.5 mg orally every day. This medication is also recognized to lessen myocardial infarctions, strokes, and fatalities. Moreover aside from changes in medications can make other alterations such as diet change, smoking cessation, weight loss, provision of health education from medical professionals and physical activity is required (Mayor, 2017).
Conclusion
The majority of deaths globally are currently caused by cardiovascular disorders, and diabetes is frequently found in these people. It is thought that people with type diabetes are more likely than non-diabetics to die from cardiovascular illnesses. In order to get the best results in the management of cardiovascular diseases which aims to maximize the benefits of available treatments while minimizing patient harm clinicians must possess basic knowledge of pharmacokinetics and pharmacodynamics (Rosenthal. & Burchum, 2018).
References
Hoover, L. E. (2019). Cholesterol management: ACC/AHA Updates guideline. Https://eds-a- ebscohost-com-ezp.waldenulibrary.org/eds/pdfviwer/
Mayor, S. (2017). Pharmacokinetics: Optimizing safe and effective prescribing. Https://onlinelibrary.wiley.com/doi/pdf/10.1002/psb.1551
Rosenthal, L.D. & Burchum. J.R. (2018). Lehne’s pharmacotherapeutics for advanced practice providers. St. Louis, MO: Elsevier.
Sieder, S. T., Kalus, J. & Lanfear, D. E. (2016). Cardiovascular pharmacokinetics, Pharmacodynamics and Pharmacogenomics for the clinical practitioner. Https://eds-a- ebscohost-com.ezp.waldenulibrary.org/eds/delivery/
Mancia, G., Fagard, R., Narkiewicz, K., Redon, J., Zanchetti, A., Böhm, M., & Galderisi, M. (2014). 2013 ESH/ESC Practice guidelines for the management of arterial hypertension: ESH-ESC: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Pressure, 23(1), 3-16.
Mangoni, A. A., & Jarmuzewska, E. A. (2019). The influence of heart failure on the pharmacokinetics of cardiovascular and non‐cardiovascular drugs: A critical appraisal of the evidence. British Journal of Clinical Pharmacology, 85(1), 20-36.
Discussion: Pharmacokinetics and Pharmacodynamics
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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.
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
As an advanced practice nurse assisting physicians in the diagnosis and treatment of disorders, it is important to not only understand the impact of disorders on the body, but also the impact of drug treatments on the body. The relationships between drugs and the body can be described by pharmacokinetics and pharmacodynamics. Pharmacokinetics describes what the body does to the drug through absorption, distribution, metabolism, and excretion, whereas pharmacodynamics describes what the drug does to the body.
When selecting drugs and determining dosages for patients, it is essential to consider individual patient factors that might impact the patient’s pharmacokinetic and pharamcodynamic processes. These patient factors include genetics, gender, ethnicity, age, behavior (i.e., diet, nutrition, smoking, alcohol, illicit drug abuse), and/or pathophysiological changes due to disease. In this Discussion, you reflect on a case from your past clinical experiences and consider how a particular patient’s pharmacokinetic and pharmacodynamic processes altered his or her response to a drug.
To prepare:
Review this week’s media presentation with Dr. Terry Buttaro, as well as Chapter 2 of the Arcangelo and Peterson text, and the Scott article in the Learning Resources. Consider the principles of pharmacokinetics and pharmacodynamics.
Reflect on your experiences, observations, and/or clinical practices from the last five years. Select a case from the last five years that involves a patient whose individual differences in pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug. When referring to your patient, make sure to use a pseudonym or other false form of identification. This is to ensure the privacy and protection of the patient.
Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.
Think about a personalized plan of care based on these influencing factors and patient history in your case study.
With these thoughts in mind:
By Day 3
Post a description of the case you selected. Then, describe factors that might have influenced pharmacokinetic and pharmacodynamic processes of the patient from the case you selected. Finally, explain details of the personalized plan of care that you would develop based on influencing factors and patient history in your case.
By definition, pharmacokinetics studies how the body absorbs, distributes, metabolizes, and excretes drugs, while pharmacodynamics observes the biochemical and physiological effects that specific drug concentrations produce in the body (PharmaEducation, 2021). Both concepts represent primary divisions of clinical pharmacology and equate to roughly 25% of the information included on a drug’s safety label.
Additionally, they provide insight into the relationship between medication dose and response and help determine a drug’s safety and efficacy (Keller & Hann, 2018). Therefore, clinicians must apply pharmacokinetic and pharmacodynamic principles throughout the treatment process to ensure they are addressing the physiological characteristics of patients most effectively while reducing the risk of harm (Thürmann, 2020).
Age-related physiologic changes affecting pharmacokinetics and pharmacodynamics in the elderly may cause decreased hepatic metabolism or renal excretion of drugs and increased sensitivity to specific classes of medications, all of which can result in toxicity or altered drug responses among this population (Thürmann, 2020). One particular incidence I recall regarding this phenomenon was an opioid-naive, frail, and petite female patient in her mid-seventies who underwent a left hip arthroplasty secondary to a femoral neck fracture resulting from a fall. Before the operation, she was alert and oriented without any cognitive concerns.
However, after waking from surgery, she gradually began experiencing restlessness, confusion, short-term memory loss, impulsiveness, and hallucinations (Wan & Chase, 2017). As it turns out, she was experiencing delirium, likely in response to the amount of general anesthesia given during surgery, sensitivity to the combination of opioid medications givens before and after surgery, and her kidney’s inability to excrete the administered drugs effectively, as indicated by a reduced glomerular filtration rate (GFR).
As an advanced practice registered nurse, a personalized care plan I would develop to address this patient’s pharmacokinetic and pharmacodynamic changes will be analyzing her kidney functioning using the eGFR, performing thorough medication reconciliation, and looking for opportunities to “deprescribe” unnecessary medications upon her admission (Davies, 2017). When it comes to prescribing pain medications, we will start low and go slow with analgesics, being sure to avoid using multiple drugs from the same or similar class (Thürmann, 2020).
Furthermore, we will maximize opportunities to use nonpharmacologic interventions such as repositioning, applying cold compresses, and providing comfort measures (Keller & Hann, 2018). Other multicomponent interventions we will initiate to avoid adverse drug effects will be monitoring signs of infection, preventing dehydration, promoting mobility, and supporting healthy sleep patterns in the pre and postoperative stages (Wan & Chase, 2017).
References
Davies, P. S. (2017). Opioids for pain management in older adults. The Nurse Practitioner, 42(2), 20–26. https://doi.org/10.1097/01.npr.0000511772.62176.10Links to an external site.
Keller, F., & Hann, A. (2018). Clinical pharmacodynamics. Clinical Journal of the American Society of Nephrology, 13(9), 1413–1420. https://doi.org/10.2215/cjn.10960917Links to an external site.
Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.
Thürmann, P. A. (2020). Pharmacodynamics and pharmacokinetics in older adults. Current Opinion in Anaesthesiology, 33(1), 109–113. https://doi.org/10.1097/aco.0000000000000814Links to an external site.
Wan, M., & Chase, J. (2017). Delirium in older adults: Diagnosis, prevention, and treatment. BC Medical Journal, 59(3), 165–170. https://bcmj.org/articles/delirium-older-adults-diagnosis-prevention-and-treatment
Discussion: Pharmacokinetics and Pharmacodynamics
By Day 6
Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional patient factors that might have interfered with the pharmacokinetic and pharmadynamic processes of the patients in their cas
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