NURS 6521 PHARMACOKINETICS AND PHARMACODYNAMICS

NURS 6521 PHARMACOKINETICS AND PHARMACODYNAMICS

NURS 6521 PHARMACOKINETICS AND PHARMACODYNAMICS

I had a recent clinical experience where a patient of mine was sensitive to medications. She had recently had high blood pressure in the 200’s and acute kidney failure. She was given IV hydralazine and labetalol in the emergency room. She had a reaction to the medication and her heart rate dropped into the 20’s and she became unresponsive. The emergency room staff performed chest compressions and administered to the patient, and she was transferred to the ICU.

A case study writes about adverse effects of hydralazine and notes “Hydralazine was chosen for its antihypertensive effect and 2 mg were administered intravenously (IV). Within a brief period of time (30-45 sec) the patient developed a profound bradycardia from 52-10 beats/min occasioned by premature ventricular contractions (PVCs)” (Wehner & Romanauskas, 1981). A different case study notes a similar adverse effect of labetalol, “She was thought to have an anaphylactoid reaction and was treated intravenously with fluids, diphenhydramine (50 mg), and methylprednisolone (250 mg), without initial improvement. While urinating in the bedpan, she developed bradycardia and hypotension, with a pulse of 30/min and a blood pressure of 60/40. Trendelenburg’s position and 2 L of normal saline were needed to restore her blood pressure to normal, although her bradycardia resolved spontaneously” (Ferree, 1986).

This patient had orders to receive hydralazine IV to maintain a blood pressure of 140/80 so that she could have a kidney biopsy. “Most patients who undergo renal biopsy have hypertension, but hypertension is almost never considered a single or leading indication for biopsy” (Stompór & Perkowska-Ptasińska, 2020).

I diluted the hydralazine and pushed it over 10 minutes minimum and monitored the patient closely. I checked her blood pressure 15-30 minutes after administration and monitored her heart rate. She did not have any adverse reaction to the hydralazine when I administered it. I instructed the patient to use her call light button if she had any strange reactions or felt odd. I kept the physician updated on the patient’s blood pressure and heart rate throughout the night. The patient was able to transfer to a medical-surgical floor for a lower level of care.

References

FERREE, C. E. (1986). Apparent Anaphylaxis from Labetalol. Annals of Internal Medicine104(5), 729–730. https://doi-org.ezp.waldenulibrary.org/10.1059/0003-4819-104-5-729_2Links to an external site.

Stompór, T., & Perkowska-Ptasińska, A. (2020). Hypertensive kidney disease: a true epidemic or rare disease? Polish Archives of Internal Medicine130(2), 130–139. https://doi-org.ezp.waldenulibrary.org/10.20452/pamw.15150Links to an external site.

Wehner RJ, & Romanauskas VS. (1981). An adverse reaction with hydralazine: a case study. AANA Journal49(3), 274–276.

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Hey thanks for sharing informative post, as we are aware Pharmacokinetic process includes four main steps such as absorption, distribution, metabolism, and excretion that explain movement of drug throughout the body. Applying detailed knowledge of these four steps to drug therapy will be beneficial in achieving maximum effects of drugs and minimize harm .IV hydralazine is usually used in the hospitalized patient with hypertensive emergency. The pattern of drug absorption such as rate and extent of absorption is unique and the route by which the drug is administered significantly affects both the onset and intensity of effects (Rosenthal and Burchum, 2021, p 13). However as mentioned in the scenario patient was given IV hydralazine hence the absorption phase is bypassed and absorption happens instantaneous with rapid onset, and precise control over drug levels can be maintained. It is very critical to dilute the IV hydralazine with 10cc of sodium chloride prior to its administration and should be injected slowly over 2 minutes to avoid precipitous decrease in arterial pressure with a critical reduction in cerebral and utero-placental perfusion. This process or administration of 5-10 mg of IV hydralazine can be repeated every 20-30 minutes until the desired effect is achieved however the blood pressure and heart rate of patient should be monitored entire time. Hypotensive effects occur 5-30 minutes after an IV dose. The antihypertensive effects of an IV dose last 2-6 hours on average, although the effects of a parenteral dose can last up to 12 hours; the affinity of hydralazine for arterial walls may partially explain the prolonged effect. The patient here in the scenario is admitted with hypertension and acute kidney failure so it is also critical to consider pharmacokinetic parameters such as drug excretion as the majority of the drug excretion occurs via kidneys and in the case of acute renal failure both the duration and intensity of drug responses may increase. Hence it is important to check on creatinine clearance levels and adjust the dose based on its function.

NURS 6521 PHARMACOKINETICS AND PHARMACODYNAMICS
NURS 6521 PHARMACOKINETICS AND PHARMACODYNAMICS

References

hydralazine hydrochloride – Drug Summary. PDR.net. (n.d.). Retrieved December 2, 2022, from https://www.pdr.net/drug-summary/Hydralazine-Hydrochloride-Tablets-hydralazine-hydrochloride-738

Hydralazine 20mg Powder for Concentrate for Solution for Injection/Infusion. ADVANZ PHARMA. (2022, August 8). Retrieved from https://www.medicines.org.uk/emc/product/6710/smpc#gref

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

As a preoperative nurse, nurses administer versed and fentanyl on a daily basis as directed by the anesthesiologist’s orders. While other

drugs are given, this is primarily an orthopedic facility and these are the most commonly given pre-op drugs, especially for sedation for

nerve blocks.  Patients’ ages range from small children to elderly and medical history varies vastly among each patient. To establish

desired effect, but avoid causing harmful side effects, the appropriate dosage must be given. For patients with an intravenous (IV) access,

these drugs have instantaneous absorption with rapid onset (Rosenthal & Burchum, 2021). Dependent upon the patient’s age, frequency

of use of analgesics, and size the anesthesiologist decides on the dosage to be given prior to initiation of a nerve block. Generally

speaking, most patients reach the desired pleasant state resulting in minimal discomfort during the short procedure. However, there are

two instances that come to mind and that is the patients that, for different reasons, have very high tolerance to some medications and

then those who are “light weights” as we tend to refer to them. However, older patients typically require smaller dosages of versed and

fentanyl. Sometimes the versed is even omitted and a lesser amount of fentanyl is given to avoid over sedation and confusion. Drug

sensitivity varies across the lifespan, but infants and elderly patients have increased sensitivity to drugs (Rosenthal & Burchum, 2021).

Usually, the anesthesiologists are great at judging what dosage is appropriate for each patient, but sometimes the tiny, elderly patients

can be easily over sedated. When this happens, mental status is altered and oxygen saturation, respiratory, and heart rate may drop.

Although fentanyl has an onset of less than sixty seconds, ninety minute half-life, and thirty to sixty minute duration of action with peak

affect at two to five minutes; older adults metabolize drugs more slowly (Rosenthal & Burchum, 2021). In older adults, absorption rate is

altered because of delayed gastrointestinal transit time. Drug distribution is affected as a result of less lean body mass and water within

the body. Other considerations for older adults are reduction in hepatic blood flow as well as renal elimination of drugs. Normally

fentanyl is redistributed to sites such as fat and muscle, pretty much exclusively metabolized by the liver with a small percentage

excreted by the kidneys (Peng & Sandler, 1999).  Due to the body’s pharmacokinetic and pharmacodynamics changes with aging, opioids

dosage should be reduced by 25-50% as compared to that given to a younger patient (Chau, et al., 2008). In addition to low flow nasal

cannula and pulse oximetry during the procedure, robinul can be given to decrease bradycardic affects for these patients (Gallanosa &

Quick, 2019). Each patient should be personally evaluated for medical history, medication reconciliation done, medications taken that

day noted, and weight noted prior to administering these drugs.

 References

Chau, D. L., Walker, V., Pai, L., & Cho, L. M. (2008). Opiates and elderly: use and side effects. Clinical interventions in aging, 3(2), 273–     

           278. https://doi.org/10.2147/cia.s1847Links to an external site.

Gallanosa, A., & Quick, J. (2019). Glycopyrrolate. Nih.gov; StatPearls Publishing.    

          https://www.ncbi.nlm.nih.gov/books/NBK526035/Links to an external site.

Peng, P. W. H., & Sandler, A. N. (1999). A Review of the Use of Fentanyl Analgesia in the Management of Acute Pain in Adults.

           Anesthesiology, 90(2), 576–599. https://doi.org/10.1097/00000542-199902000-00034Links 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

I agree that Pharmacokinetics plays a huge role on the effects of pain medication. I just have a recent experience where a patient was admitted to my floor and was later sent to surgery to receive split thickness graft to her BLE. The patient blood pressure began to slowly drop, and respirations became shallow after the administration of versed. The patient was 78 years old and was 78kg. The patient had to  receive Narcan because of the medication. Later it was found that the patient had a Hydromorphone pump and was receiving Hydromorphone and sedatives while in surgery. Sedates are usually given based off the patients age and weight. Pharmacokinetics and pharmacodynamics occur differently in older adults.  Older adults typically have decreased gastric acid production and decreased gastric mobility which causes impaired drug dissolution (Rosenthal et al.,2021,p.60). This can cause decrease bioavailability of drugs. Decreased gastric mobility in adults increases the effects of medications (British Pharmacological Society, 2022, p.4).

British Pharmacological Society | Journals – Wiley Online Library. (n.d.). Retrieved December 4, 2022, from https://bpspubs.onlinelibrary.wiley.com/ 

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

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-reviewLinks to an external site.

Gestational hypertension: Causes, symptoms & treatment. (2022). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4497-gestational-hypertensionLinks to an external site.

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-deliveryLinks to an external site.

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/Links to an external site.

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/Links to an external site.

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/Links to an external site.