DNP 810 How does the variability of responses result in tailoring pharmacologic agents to the care of these patients?
DNP 810 How does the variability of responses result in tailoring pharmacologic agents to the care of these patients?
DNP 810 How does the variability of responses result in tailoring pharmacologic agents to the care of these patients?
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.
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.
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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
Healthcare continues to move away from a cookie-cutter approach or a one size fits all. With the advent of the human genome, therapies and treatments are targeted to meet the individual need of the patient. Using precision medicine, genetic information, environment, and lifestyle can be considered to target treatment and improve outcomes. When given the same medication, there can be unique and individual responses. Providers need to understand this potential complication and interaction with individual genetics. Medications with narrow therapeutic windows or side effects could cause life-threatening complications. As with other areas in healthcare, studies have not included minority races which contribute to social determinants of health and health inequities (Borrell et al., 2021). Including minority groups is imperative if precision medicine is truly going to target the uniqueness of each individual. Beyond the race or ethnicity of a person, which is socially ascribed, providers should consider genetic ancestry (Borrell et al., 2021). This represents the person’s genetic origin which is more specific and detailed to the exact but variable makeup of the individual. This more detailed information teases out some of the variations found in large race or ethnicity groups.
Certain medications impact individuals differently. For example, there are different classes of medications that are prescribed to address hypertension such as beta-blockers, calcium channel blockers, ace inhibitors, or diuretics. Hypertension can be a complex genetically acquired condition. However, genetics can impact the effectiveness of different classifications of anti-hypertensive medications. Targeting individual genotypes can produce a better response to antihypertensive medications. However, studies researching the effectiveness of the various classes of medications are inconclusive which may be due to interethnic differences (Rysz et al., 2020). Single nucleotide polymorphisms (SNPs) are considered to play a role in the inter-individual variation that can be seen with treatment response. Just as hypertension is complex and multi-causal, genetic traits are only a part of the explanation for treatment effectiveness. Treatment response for hypertension is multifaceted, just like the disease itself. With more research and understanding of the different alleles and SNPs involved in hypertension and the effects of the medication, treatments, especially in regard to pharmacogenetics, will be able to be targeted to the genetic picture of the patient.
References
Borrell, L. N., Elhawary, J. R., Fuentes-Afflick, E., Witonsky, J., Bhakta, N., Wu, A. H. B., Bibbins-Domingo, K., Rodríguez-Santana, J. R., Lenoir, M. A., Gavin, J. R., Kittles, R. A., Zaitlen, N. A., Wilkes, D. S., Powe, N. R., Ziv, E., & Burchard, E. G. (2021). Race and Genetic Ancestry in Medicine — A Time for Reckoning with Racism. N Engl J Med, 384(5), 474-480. 10.1056/NEJMms2029562
Rysz, J., Franczyk, B., Rysz-Górzyńska, M. & Gluba-Brzózka, A. (2020). Pharmacogenomics of hypertension treatment. International Journal of Molecular Science, 21 (13), 4709. Doi: https://doi.org/10.3390/ijms21134709.