ORCID

https://orcid.org/0009-0009-1339-0590

Date of Award

2024

Document Type

Dissertation

Degree Name

Philosophy (Ph.D)

Department

Pharmaceutical Sciences

First Advisor

Marc Gillespie

Second Advisor

Yasmine Lashine

Third Advisor

Sunil Kumar

Abstract

Managing pain requires a delicate balance between the advantages of opioid analgesia and the possible adverse effects. This balance becomes even more difficult in hospice and palliative care environments where dosage regimens are frequently ambiguous. Some hospice patients experience opioid resistance, in which opioids no longer produce an analgesic effect on a patient. Evidence-based analyses frequently omit this vulnerable population, resulting in a need for concrete procedures. The emergence of pharmacogenomic analysis and personalized treatment presents a solution to this problem by using each patient's genomic data to interpret opiate dosing. This pharmacogenomic study aimed to single nucleotide polymorphisms (SNPs) influencing opioid response in 18 hospice patients aged 37-84 years (mean 63 years, 72% male). Participants had diagnoses including COPD, cancer, and HIV. Buccal swabs provided DNA for 50-gene panel genotyping. Medical records supplied demographic information, medication lists, chronic health conditions, morphine doses, pain scores, and palliative performance status data. Linear regression analysis identified single nucleotide polymorphisms (SNPs) significantly impacting outcomes. According to genomic analysis, individuals with the non-TT genotype of the CNR1 gene were found to require, on average, a dose of morphine that was 102.3 mg lower than the dose required by individuals with the TT genotype of the same gene (p=0.031). The SLCO1B1 genotype and intermediate activity phenotype reduced average pain (p=0.046). The COMT non-MET homozygous phenotype increased maximum pain versus MET homozygotes (p=0.041). The CYP2B6 genotype and G516T heterozygous/A785G homozygous phenotype decreased maximum pain (p=0.050). The CYP4F2 poor metabolizer phenotype increased palliative performance versus other CYP phenotypes (p=0.028). These findings show that genetic variants can modulate opioid metabolism and pain response in hospice patients. This study marks an essential step towards the goal of personalized medicine in pain management at the end of life, suggesting that genotype- guided opioid dosing regimens could potentially lead to improved pain management. However, the sample size of 18 of this pioneering pharmacogenomic study in hospice patients underscores the need for larger-scale studies to validate the predictive utility of our findings.

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