Sample Answer for NURS 6521 Describe how changes in the pharmacokinetic and pharmacodynamic processes might impact the patient’s recommended drug therapy Included After Question
Patient AO has a history of obesity and has recently gained 9 pounds. The patient has been diagnosed with hypertension and hyperlipidemia. Drugs currently prescribed include the following:
- Atenolol 12.5 mg daily
- Doxazosin 8 mg daily
- Hydralazine 10 mg qid
- Sertraline 25 mg daily
- Simvastatin 80 mg daily
Write a 3-page paper that addresses the following:
(Including the Introduction and conclusion)
- Explain how the age factor might influence the pharmacokinetic and pharmacodynamic processes in the patient from the case you were assigned.
- Describe how changes in the pharmacokinetic and pharmacodynamic processes might impact the patient’s recommended drug therapy. Be specific and provide examples.
- Explain how you might improve the patient’s drug therapy plan by changing medications or provide an alternative treatment option for the patient.
A Sample Answer For the Assignment: NURS 6521 Describe how changes in the pharmacokinetic and pharmacodynamic processes might impact the patient’s recommended drug therapy
Title: NURS 6521 Describe how changes in the pharmacokinetic and pharmacodynamic processes might impact the patient’s recommended drug therapy
Pharmacokinetics and pharmacodynamics determine the clinical effects of drug therapy. Pharmacokinetics (what the body does to the drug) is defined as the quantitative study of drug absorption, distribution, metabolism, and elimination (ADME). Pharmacodynamics is clinically more elusive and difficult to precisely quantify. Pharmacodynamics is the study of the biochemical and physiological effects of drugs in the body. Thus, pharmacodynamics can be thought of as “what the drug does to the body.” Despite being 2 distinct entities, there is substantial interplay between pharmacokinetics and the resultant pharmacodynamics. Understanding this can be challenging. The correlation between the dose administered and the resulting drug concentration at the site of action ultimately contributes to the pharmacodynamic response. Thus, pharmacodynamics describes the relationship between drug concentration and the desirable clinical effects of a medication as well as unwanted adverse effects. In addition, in pediatric patients, growth and development affect pharmacokinetics and pharmacodynamics. This article reviews the interplay between pharmacokinetics and pharmacodynamics (ie, dose-exposure-response relationships).
Pharmacokinetics
Pharmacokinetics (ADME) determines the concentration or amount of drug in the body that is available to have the desired effect. For a drug to have a positive or negative effect internally, the medication must first enter the body (eg, ingestion, dermal, rectal, submucosal) and be absorbed into the bloodstream. Once in the bloodstream, the drug can be distributed, ultimately reaching the site in the body where it may produce the desired effect at a receptor or drug target. After the drug-receptor interaction, the medication returns to the bloodstream and is taken to the liver, where it can be metabolized to substances that are more easily eliminated in the urine or feces.
Absorption
Absorption is the process by which a drug enters the bloodstream or another body compartment from the site of administration. Bioavailability is defined as the rate and extent to which the active drug is absorbed and becomes available at the site of drug action to produce a pharmacologic response. Drugs administered via the intravenous route are considered to be 100% bioavailable, meaning that the entire drug dose has reached the circulation. Routes that require absorption include oral, intramuscular, subcutaneous, and topical/transdermal and can result in adverse effects if given in sufficient quantities. Drug absorption plays a pivotal role in determining pharmacodynamic responses.
For a drug to be absorbed into the circulation, the active drug must first be liberated from the dosage form. Liberation depends on physiochemical factors of the drug, the dosage form, and the environment at the site of administration. There are multiple mechanisms by which drugs are absorbed into the circulation, including passive diffusion, convective transport, active transport, facilitated transport, ion pair transport, and pinocytosis. Except in the case of pinocytosis, a drug must be released into solution to be absorbed.
Passive diffusion is one of the most important mechanisms of drug absorption; however, active transporters such as P-glycoprotein (P-gp) can be particularly important owing to drug-drug and drug-food interactions. P-glycoprotein is a transporter located in the endothelium of multiple organs, including the gastrointestinal tract lumen and the blood-brain barrier. This efflux transporter is responsible for pumping drugs back into the gut lumen and decreasing bioavailability. Digoxin is an example of a drug that is transported by P-gp. Inhibition of P-gp will increase the bioavailability of a P-gp substrate such as digoxin, and, conversely, induction of P-gp will reduce the bioavailability of digoxin and other P-gp substrates. This type of interaction has direct relevance to the clinical setting. For example, erythromycin, clarithromycin, and quinidine are P-gp inhibitors and, thus, when coadministered with digoxin, can result in an increased serum digoxin concentration. Grapefruit juice, guava, and mango also inhibit P-gp and can similarly affect the bioavailability of P-gp substrates. In addition to P-gp, other patient-specific factors, such as age, sex, body weight, gastric emptying rate, intestinal motility, gastric pH, blood flow, liver function, length of the intestines (short gut syndrome), type of diet, and presence/absence of food, can modify the efficiency and rate of absorption.
Absorption of a drug and the resulting serum concentration can depend on food intake and the time to medication exposure (Table 1). Medications are weak acids or weak bases that become ionized or un-ionized depending on the pH in the environment in which absorption takes place. Consuming a medication in the presence or absence of food can change the ionization state of the medication and affect absorption. Some medications are destroyed by stomach acid and should be taken on an empty stomach because food increases acid secretion. In addition, foods such as grapefruit juice can inhibit the intestinal enzyme cytochrome P450 (CYP) 3A4, resulting in increased drug absorption and higher serum concentrations. Insulin and oral antidiabetic agents are generally recommended to be administered with food to prevent hypoglycemia. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids should be administered with food to prevent local gastric irritation and ulceration.
Patient Scenario
Jane Doe is a 32-year-old G4P4 who vaginally delivered a viable female infant at 0804 this morning. Two hours post-delivery the patient comes over to the postpartum unit, and report is obtained from the labor & delivery (L&D) nurse. This same nurse attended her delivery and cared for her throughout her recovery. She reported that the patient had an uncomplicated delivery, infant weighed 3573 grams, a first-degree perineal laceration was noted and repaired, her quantitative blood loss was 250 milliliters. The patient has an 18 gauge IV in her left hand. Her fundus is noted to be firm, midline, and at the level of the umbilicus. The patient is planning to breastfeed her infant. The L&D nurse states that the patient attempted but was unable to void after the delivery prior to transferring to postpartum. The patient denies any pain currently. Jane Doe had an adequate and uncomplicated course of prenatal care. Her medical history includes gestational hypertension for which she has been taking Labetalol 200mg twice daily during her pregnancy, lupus, anxiety, and depression. She is unmedicated for the latter diagnoses.
Her blood pressures have been closely monitored and have been under control in the 130s/70s-80s throughout her pregnancy. She does admit to smoking 1/2 pack per day for the last 15 years but has no history of drinking alcohol. Her BMI is within normal range, and she has no family history of hypertension. Her vital signs upon admission to postpartum are T:98.3, P:110, BP:165/93, RR:20, SpO2:99% on room air. The patient’s vital signs were stable during her labor, delivery, and recovery with only slightly elevated blood pressure but nothing of concern. The patient’s lab work and urinalysis that was obtained prior to delivery was all within normal limits. Jane Doe is given her morning dose of Labetalol 200mg at the time of admission. The nurse will reassess her blood pressure 1 hour after administration and report to the doctor.
Factors Influencing Pharmacokinetics
The antihypertensive drug Labetalol is an alpha-beta blocker. Its use is recommended for treating gestational hypertension as it is safe for pregnant women and their unborn child. It is also safe for breastfeeding mothers. Labetalol relaxes blood vessels leading to a decrease in blood pressure and heart rate (Khan, 2020). The extent of decrease in blood pressure depends on the route of administration of Labetalol. In oral administration, a drop in blood pressure can be seen 20 minutes to 1 hour after administration, while effects from IV administration can be seen in just minutes. Labetalol is absorbed rapidly via first pass metabolism into the blood plasm through the liver or gastrointestinal tract. The highest concentration levels are seen at around 1-2 hours post administration. Labetalol’s half-life is approximately 3-3.5 hours after administration.
The bioavailability is shown to correlate with the age of the patient with values of only 30% seen in patients aged 30-40. My patient falls in this age range at 32 years old. The bioavailability is noted at higher levels in older patients doubling to 60% at the age of 80. This percentage is also noted to increase when the medication is taken with food. The liver is responsible for excretion of Labetalol. After a dose of Labetalol is administered to a patient, the hepatic system rids the blood stream of approximately 85% of the medication. Excretion of Labetalol is dependent on the quality of hepatic blood flow. Labetalol is metabolized through conjugation to glucuronide metabolites and is excreted via urine and bile in feces (Abdullah & Yusof, 2019).
Factors Influencing Pharmacodynamics
Labetalol is a dual action medication. It is both an alpha1-adrenergic antagonist and a beta-adrenergic antagonist. Labetalol selectively antagonizes alpha1-adrenergic receptors and non-selectively antagonizes beta-adrenergic receptors, therefore the activity ratio of alpha to beta blockage when administered via the oral route is 1 to 3. When administering via the intravenous route the ratio is 1 to 7 (Miller et al., 2022). When Labetalol is administered, alpha1-adrenergic antagonism occurs which lowers blood pressure by vasodilation and a decrease in vascular resistance. Continued vasodilation from Labetalol use will not decrease stroke volume or cardiac output. Beta-adrenergic antagonism causes a decrease in the patient’s heart rate. Labetalol stops adrenergic stimulation of β-receptors in the smooth muscles, cardiac muscles, and bronchial muscles. This blockade is what causes a decrease in systemic blood pressure. This process also elicits some of the side effects caused by Labetalol such as bronchospasms. For this reason, Labetalol is contraindicated in patients with asthma (Abdullah & Yusof, 2019).
Personalized Plan of Care
The plan moving forward for Jane Doe was to recheck her blood pressure 1 hour after administration of Labetalol 200mg. Her blood pressure remained elevated at 160/99. I notified the provider who increased her Labetalol dose to 300mg three times daily. At this time, I administered the extra dose of 100mg of Labetalol to equal the newly ordered dosage, and her blood pressure was rechecked again in 1 hour. The patient’s blood pressure did respond to the extra dose of Labetalol, and her blood pressure dropped to 135/80. Increasing the strength and frequency of the medication kept the concentration levels in her body at a higher percentage throughout the day to control her blood pressure. Going forward, her blood pressures were checked every four hours or more frequently as needed throughout her stay. The nurses on each shift assessed for edema, changes in vision, and daily weight checks were performed. Gestational hypertension is high blood pressure that develops after 20 weeks gestation, and it usually subsides after delivery of the infant. In this patient’s case, the blood pressure did not immediately return to normal range.
She will likely have to remain on the Labetalol for the next couple weeks. She will follow up in the office with her OBGYN in 1 week for a blood pressure check. There are a few factors that could have caused this. The patient could have an overabundance of fluid onboard from receiving intravenous fluids before, during, and after her delivery. The patient also has a history of lupus which puts her at greater risk for gestational hypertension. Gestational hypertension also makes this patient more susceptible for developing chronic hypertension later in life. The patient’s history of smoking for the past 15 years is a major factor that can contribute to hypertension. I educated her on smoking cessation. If this patient’s blood pressure had not decreased our next plan of action would have been to transfer her back to Labor & Delivery and begin a magnesium drip to control her blood pressure. This is recommended for emergency treatment to reduce the risk of preeclampsia induced seizures (Morgan, 2021).
References
Abdullah, A., & Yusof, M. (2019). Labetalol: A brief current review. Pharmacophore. https://pharmacophorejournal.com/article/labetalol-a-brief-current-review
Gestational hypertension: Causes, symptoms & treatment. (2022). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4497-gestational-hypertension
Hypertension during pregnancy and after delivery: Management, cardiovascular outcomes and future directions. (2018, September 28). American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2018/09/28/08/08/hypertension-during-pregnancy-and-after-delivery
Khan, A. (2020, April 10). Taking Labetalol in pregnancy: Is it safe, risks & side effects. FirstCry Parenting. https://parenting.firstcry.com/articles/taking-labetalol-in-pregnancy-is-it-safe/
Miller, M., Kerndt, C. C., & Maani, C. V. (2022, July 12). Labetalol – StatPearls – NCBI bookshelf. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK534787/
Morgan, J. (2021, February 23). Postpartum hypertension: When a new mom’s blood pressure is too high | Heart | Your pregnancy matters | UT southwestern Medical Center. UT Southwestern Medical Center | The #1 Best Hospital in DFW. https://utswmed.org/medblog/postpartum-high-blood-pressure/
Grading Rubric
| Performance Category | 100% or highest level of performance
100% 16 points |
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88% 14 points |
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Inadequate demonstration of expectations
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56% 9 points |
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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. |
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