response

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 pharmacodynamic processes of the patients they described. In addition, suggest how the personalized plan of care might change if the age of the patient were different and/or if the patient had a comorbid condition, such as renal failure, heart failure, or liver failure.

Peer 1

Pharmacokinetics is the science that analyzes how the human body interacts with a drug. It examines how drugs are absorbed, distributed, metabolized, and excreted by the body. Pharmacodynamics focuses on the biochemical and physiologic effects of drugs and their organ-specific mechanism of action, including effects on the cellular level.

 

As an RN, I have cared for numerous older adults suffering from chronic to acute pain associated with injuries they sustained from falls.  Recently, I had a patient suffering from severe pain due to an injury from a fall. The report from a previous nurse who helped the patient indicates that the patient at baseline was A&Ox4; however, now the patient is alert to self only with visual and auditory hallucinations.  When I reviewed the patient’s H&P, the patient has stage-3 kidney disease and is on Morphine 2mg q2hrs, oxycodone 10mg q4hrs, and Tylenol for pain control.  The patient’s MAR shows that the patient was taking both Oxycodone, Morphine, and Tylenol often together.

 

Age-related changes can affect the pharmacokinetics and pharmacodynamics of an opioid, thereby changing both the intensity and duration of analgesia (Rogers et al., 2013). Typically, opioids are metabolized by the liver and excreted in the urine or feces. Decreased hepatic and renal clearance often occurs with advancing age, leading to an increased half-life and decreased excretion of drugs cleared by the liver/kidney. In addition, older persons have an increase in body fat (20%–40% on average), leading to an increased volume of distribution for fat-soluble drugs (Hutchinson & O’Brien, 2007). As age-related changes in gastrointestinal absorption function to lower gastrointestinal transit times and the possibility of increased opioid-related dysmotility, in older adults, the elimination of Lipid-soluble opioids, such as fentanyl, from the body may take longer times.

 

Considering these factors, during morning rounds, I discussed with the provider a care plan that may help the patient with his pain besides opioids. I planned to try lidocaine patch warm packs and reduce Oxycodone from 10mg to 5mg and Morphine from 2mg to 1mg only during PT therapy, not at the same time as Oxycodone, and scheduled Tylenol. The provider agreed with the plan of care.  At the end of my shift, the patient’s mental status improved. The patient’s pain was well controlled.  

 

Peer 2

Post a description of the patient case from your experiences, observations, and clinical practice from the last five years.

A recent case that comes to mind would be a 76-year-old male who was diagnosed with new heart failure. The patient had recent bouts of extreme shortness of breath and fatigue. He was found to have left-sided heart failure with an ejection fraction of 20%. He had not been seen by a primary care doctor in over 20 years and had a long list of medical problems and non-compliant behaviors. He was a functioning diabetic with an A1C of 12.3, unmedicated, and very little dietary compliance. He had some existing kidney failure with a creatine of 2.01 and was a two-pack-a-day smoker.

Factors that might have influenced pharmacokinetics.

The pharmacokinetics involved with this patient would be to study his body's relationship with any treatments initiated to treat his heart failure. The absorption of any HF medications could be altered in this patient due to his diabetes, which would cause decreased or sluggish blood flow. DM can also significantly impact gastric emptying and the PH of gastric plasma, dramatically affecting the drug's partitioning during absorption. It is believed that the more extended amount of time spent in an acidic environment causes drugs to be more soluble and can alter the body's absorption (Stillhart et al., 2020). DM also affects the distribution due to decreased or sluggish blood flow in DM patients, especially those with high A1C. The distribution of a drug also correlates significantly with the amount of obesity in the patient, which is very common in insulin-resistant and diabetic patients. The metabolism of most drugs is regulated by Cytochrome P450 (CYP450) enzymes responsible, which is a significant variability in drug pharmacokinetics. In diabetic patients, this cytokine becomes involved in an inflammatory response and can alter the metabolism of many drugs (Gravel et al., 2018). The delayed excretion of drugs in diabetic patients can be due to microvascular changes that lead to hyperfiltration and an increased glomerular filtration rate.

The patient's undiagnosed and untreated kidney failure may also affect the passive concentration by increasing or decreasing the bioavailability of the drug, which is the absorption rate, depending on the specific medication. The distribution is affected in kidney failure because it is highly dependent on the amount of water in the body and adipose tissue. In the case of kidney disease, the changes in drug bioavailability may increase the dosage required to achieve the maximum effect (Lea-Henry et al., 2018). The most apparent alteration from kidney failure would be renal drug excretion; in all forms of kidney failure, there are alterations in glomerular filtration, passive tubular resorption, and active tubular secretion. This can cause acceleration of renal excretion of drugs, delay of renal excretion, inaccurate half-life, and the retention of certain compounds not meant for active circulation.

Pharmacodynamics

The pharmacodynamics that needs to be assessed before the distribution of any medications with this patient that the plasma drug levels would need to be monitored more closely due to his noncompliance and comorbidities that could affect the therapeutic levels required. The single dose time course would need to be observed as the patient's metabolism and excretion may change with his declining health regarding his diabetes and kidney function. The initial medication dosage would most effectively be evaluated in a hospital setting due to the half-life and dosing alterations. In this way, the clinician could have an accurate picture of the dose-response relationship and maximum efficacy in the safest way.

 

Details of the personalized plan of care that you would develop based on influencing factors and patient history in your case. 

The personalized plan of care I would develop in this case would be initiating medication in a hospital setting. The patient being untreated for multiple comorbidities, will require various medication initiation concurrently. The patient will require insulin, a diuretic, ace or ARB, or a combination of the two, and a beta blocker. The patient will be initially given lower doses due to his kidney function and the current state of his diabetes. This will all be required to be initiated with a daily comprehensive metabolic panel, complete blood count, hourly vital signs, and symptomatic response. For example, one of the most effective medications for end-stage heart failure is Entresto or Sacubitril/Valsartan, a new class of drugs called angiotensin receptor neprilysin inhibitor (ARNI). This new drug has been shown to significantly improve the ejection fraction of patients with end-stage heart failure (Kerndt et al., 2022). It could be initiated at a low dose in the hospital and monitored for subsequent hypertension, hyperkalemia, decreasing renal function, and angioedema. In this patient's case, you must consider the patient's declining renal function. Additionally, there is no history of using an ace or an ARB. Therefore you would not know if there was an allergy or adverse effect.

The patient would also start on insulin therapy due to his elevated A1C. In the hospital setting, the patient could be given a sliding-scale insulin to evaluate the effects of the drug on his blood sugar and assist him with the ongoing care that he will require when being discharged. Again, in this way is performed in the hospital, a plan of care regarding the patient's medication regimen could be in place to streamline the patient's compliance.

Due to his noncompliance, the patient would be given extensive education on each medication, its action, side effects, laboratory monitoring, interaction, and dietary restrictions. Before his discharge, a cost analysis and plan for acquiring all successful medications. He will then be given a follow-up with his primary provider, who will be established before release; he will have a consultation with the diabetes educator and the nutritionist, with subsequent follow-up. Lastly, the patient will be extensively educated on his kidney, diabetes, heart failure, and the dire need for smoking cessation.

 

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