DNP-810 Topic 4 DQ 2 Genetic/Genomic factors are known to contribute to variability of pharmacologic responses in some patients

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Topic 4 DQ 2

Jun 30-Jul 4, 2022

Genetic/Genomic factors are known to contribute to variability of pharmacologic responses in some patients. How does the variability of responses result in tailoring pharmacologic agents to the care of these patients? Explain. Support your rationale with a minimum of two scholarly sources.

REPLY TO DISCUSSION

Amanda Clark

Jul 6, 2022, 12:22 PM

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CAT: Any questions from this weeks content?

Jennifer Murillo

Jul 4, 2022, 10:54 PM

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Replies to Amanda Clark

Pharmacodynamic variability arises because of the relationship between drug concentration and effect. Within either instance, these specific genealogical variants enacting mediations pertaining to concentrations of drugs or their coinciding outcomes are increasingly being recognized as sources of variable drug action — ‘pharmacogenetics’ (Lin, 2007). Mutations, the changes in the sequences of genes in DNA, are one source of genetic variation (Lin, 2007). Another source is gene flow, or the movement of genes between different groups of organisms (Lin, 2007). Finally, genetic variation can result from sexual reproduction, which leads to the creation of new combinations of genes (Lin, 2007). When concerning responses towards administered drugs, differing populace, especially when involving ethnic vulnerability towards adverse drug reactions, are impacted when concerning polymorphisms residing within the genealogical scape. Genetic variation frequencies differ among different ethnicities, which may be associated with variation in susceptibility to adverse drug reactions among diverse populations. Variation in response to equivalent drug concentrations arises because of various factors, such as differences in receptor number and structure, receptor-coupling mechanisms, and physiological changes in target organs resulting from differences in genetics, age, and health (Lin, 2007).

Variations in drug response may be pharmacodynamic, implying inter-individual differences in the response of receptors in equal concentrations of the drug. In addition, it may also be pharmacokinetic, indicating that individuals receiving the same drug dose will have different drug concentrations in their body fluids (Hartmanshenn et al., 2016). Moreover, both inheritance and acquisition of either instance of variance are sure to follow. Variations in receptor sensitivity occur, but few inherited or acquired instances have well-documented clinical relevance. Should the therapeutic index reside at a decreased level or the causal relationship of the response as well as dosage does not retain a level of steepness, the concentration within the specific drug of the receptor region will not be critical, and causes of kinetic variation are unlikely to be clinically significant (Hartmanshenn et al., 2016). However, it is the many causes of kinetic variation, including effects due to drug formulation and changes in the absorption, distribution, metabolism, and excretion of drugs (Hartmanshenn et al., 2016). Analyzing and predicting variability due to these factors is desirable if consideration of dynamics suggests drug concentration will determine therapeutic efficacy.

References

Hartmanshenn, C., Scherholz, M., & Androulakis, I. P. (2016). Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine. Journal of pharmacokinetics and pharmacodynamics, 43(5), 481-504.

Lin, J. H. (2007). Pharmacokinetic and pharmacodynamic variability: a daunting challenge in drug therapy. Current drug metabolism, 8(2), 109-136.

Margaret Mbachu

replied toJennifer Murillo

Jul 5, 2022, 10:12 PM

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Replies to Jennifer Murillo

Thanks, Ms. Jennifer for your interesting post.

In addition, research studies conducted by Wjdan et al., have enhanced the knowledge about the physiology and biochemistry of some genetic disorders. They combined molecular techniques and classical biochemical methods to improve the detection and help in developing advanced strategies to treat patients with genetic health conditions (Wjdan, et al., 2021). Depending on the methods implemented, the outcomes must be correlated with the clinical picture and genetic variants identified by studying family history critically.

DNP-prepared nurses must be knowledgeable enough on drawbacks associated with the diagnostic approaches of genetic testing to prevent a false-negative diagnosis, validate borderline cases, and detect unusual and novel variants. Advancements in technology produced different portable and rapid devices including platforms-based immune assay, density-based separation, and sensor-based technologies to diagnose certain genetic diseases (Wjdan, et al., 2021).

Reference

Wjdan, A. A., Hani, A. A., & Mohammed, Z. (2021). Techniques for the Detection

of Sickle Cell Disease: A Review. In: Micromachines, V12 (519). p 519 2021. Retrieved

from DOI: 10.3390/mi12050519

Carolyn Smith

replied toJennifer Murillo

Jul 6, 2022, 1:11 AM

Replies to Jennifer Murillo

Hello Jennifer,

I agree with you that the relationship between drug concentration and effect triggers pharmacodynamic variability. The relationship means that people receive the same drug may have different drug concentration in their body fluids (Agueusop et al., 2020). The difference in the drug concentration depicts the nature of drug response variation in pharmacodynamic variability. Different types of variation can be acquired or inherited. Distinct variation requires different drug response. Therefore, medical experts are mandated with the obligation of helping patients to identify variation in the treatment process. Mutations, and the changes in the sequences of genes in DNA cause genetic variation (Li et al., 2019). Genetic variation may generate disorder that require immediate intervention. Unfortunately, some genetic variation incidents are as a result of hereditary transmission. As a result, determining all people in vulnerable groups may be challenging. However, medical experts ensure that they get adequate information that will guide decision-making process.

References

Agueusop, I., Musholt, P. B., Klaus, B., Hightower, K., & Kannt, A. (2020). Short-term variability of the human serum metabolome depending on nutritional and metabolic health status. Scientific reports, 10(1), 1-13.

Li, L., Knutsdottir, H., Hui, K., Weiss, M. J., He, J., Philosophe, B., … & Selaru, F. M. (2019). Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity. JCI insight, 4(2). doi: 10.1172/jci.insight.121490

Mary Benjamin

Jul 4, 2022, 7:15 PM

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Replies to Amanda Clark

About three in five Americans aged 20 years and above take prescription drugs on a monthly basis and many either encounter adverse drug reactions or reduced treatment efficacy. The strong genetic component of altered drug response in patients is well known and attributed to variants affecting drug pharmacokinetics and pharmacodynamics (Schärfe, Tremmel, Schwab, et al., 2017). Everyone’s body is different and each patient act differently to drugs, and failure to understand the variations will lead to drug toxicity and adverse drug reactions. Some of the genetic factors that could influence drug response includes, absorption, distribution, metabolism and excretion, due to body weight, genetic conditions, genetic polymorphism of drug metabolizing enzymes, height, race, receptor sensitivity, and sex.

DNP-810 Topic 4 DQ 2 Genetic Genomic factors are known to contribute to variability of pharmacologic responses in some patients

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Despite the availability of several pharmacologic treatment options for hypertension, only fewer patient of North Americans achieves target blood pressure goals. Extrinsic and intrinsic factors play a potentially different pathophysiology of hypertension in African American population and others. Polymorphism in these genes may be responsible for the high prevalence and increased severity of hypertension. Typically, African American patients require a high dosage of angiotensin-converting enzyme (ACE) inhibitors or combined therapy with low-dose diuretics to reduce blood pressure effectively.

As a DNP prepared nurse, it is important to remember that a person should be treated holistically to ensure the right drug at the right dose and the right time is prescribed to maximize the effect and minimize harm to the patient.

Schärfe, C.P.I., Tremmel, R., Schwab, M. et al. Genetic variation in human drug-related genes. Genome Med 9, 117 (2017). https://doi.org/10.1186/s13073-017-0502-5

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