PHARMACOGENOMICS
This test was not even around when I was in pharmacy school, nor when I graduated from pharmacy school in 1970. In fact, it is based on our DNA system,m and our DNA was not fully mapped until around 2000. In 2000, I was already 4 years into my FIRST RETIREMENT. By the time that PGx was really starting to gain some serious traction 10-15 yrs ago. I had decided to retire again, which ended up being my FINAL RETIREMENT. I had no real incentive to wade into the “weeds” of PGx, but I picked up enough knowledge to be “dangerous” concerning PGx.
I learned that there are some 50+ enzymes in our livers that metabolize substances we consume, and not everyone’s enzymes metabolize at the same rate. We have sl
ow, normal, fast, and ultra-fast metabolizers.
You get a pt dealing with CRPS that is a ultra-fast metabolizer and you got a pt that will need much higher single doses and typically also more frequent doses. And CRPS pts use the McGill pain scale, which is 1 to 50, not the normal 1-10 pain scale.
I ran across this type of exception to the pt’s metabolism. In this example, the pt was a NORMAL METABOLIZER
OxyCODONE
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Genotype: CYP2D6 *1/*2 (normal metabolizer), OPRM1 A118G (A/A, normal function)
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Implication: The patient should have a typical response to oxyCODONE, with no increased risk of poor pain control or opioid toxicity due to metabolism issues
The COMT Val158Met G/G genotype (Val/Val) in this patient indicates high/normal catechol-O-methyltransferase (COMT) enzyme activity, which has implications for pain perception and neurotransmitter regulation. Here’s a detailed analysis:
Biological Mechanism
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Gene: COMT (chromosome 22q11)
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Polymorphism: Val158Met (rs4680, G>A substitution)
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Enzyme Activity:
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Val/Val (G/G): ~38% higher COMT activity compared to Met/Met (A/A), leading to faster dopamine catabolism in the prefrontal cortex
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Dopamine modulates pain processing via cortico-subcortical pathways, including the endogenous opioid system.
Impact on Pain Perception
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Cognitive Pain Modulation
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Val/Val carriers show increased activation in dorsolateral prefrontal cortex (DLPFC) during pain processing, linked to cognitive control of pain
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Higher COMT activity may reduce dopamine availability, potentially diminishing top-down pain inhibition.
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Opioid Response
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Val/Val genotype is associated with higher postoperative opioid consumption, possibly due to reduced endogenous opioid signaling
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Interaction with OPRM1 (mu-opioid receptor gene): Patients with Val/Val + OPRM1 AG/GG genotypes may require larger opioid doses
Imagine having a CRPS pt who is an ultra-fast metabolizer and also has reduced dopamine levels, how many MME/day would they need to have at least a minimum of pain management?
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what is pharmacogenomics testing?
Pharmacogenomics testing, also known as pharmacogenetic testing, is a type of genetic test that analyzes a person’s DNA to determine how their genes may affect their response to specific medications125. This testing is part of the broader field of precision medicine, which aims to tailor medical treatment to individual characteristics, including genetic makeup, environment, and lifestyle15.
How Pharmacogenomics Testing Works
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Sample Collection: The test typically uses a sample of saliva, blood, or a cheek (buccal) swab125.
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Genetic Analysis: The sample is analyzed in a laboratory to identify specific genetic variants-often in genes that encode drug-metabolizing enzymes, drug transporters, or drug targets36.
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Interpretation: Results indicate whether a person may metabolize certain medications faster, slower, or at an average rate, and whether they are at increased risk for side effects or therapeutic failure235.
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Clinical Application: Healthcare providers use this information to help choose the most appropriate medication and dosage, aiming to maximize effectiveness and minimize adverse effects125.
Why Pharmacogenomics Testing Is Used
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Personalized Medication Selection: Helps predict which medications are likely to be most effective or cause fewer side effects for an individual15.
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Dose Optimization: Assists in determining the safest and most effective dose for a patient15.
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Adverse Reaction Prevention: Identifies patients at risk for serious side effects from certain medications, allowing for alternative therapies to be considered127.
Examples of Medications with Pharmacogenomics Guidance
Pharmacogenomics testing is available for a growing list of medications, including:
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Blood thinners (e.g., warfarin, clopidogrel)
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Certain antidepressants and antipsychotics
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Cancer therapies (e.g., tamoxifen)
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HIV treatments (e.g., abacavir)
Key Points
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Not everyone responds to medications the same way due to genetic differences157.
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Pharmacogenomics testing can improve treatment outcomes by guiding drug and dose selection125.
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The test is usually performed before starting a new medication or when a patient has had problems with standard treatments17.
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Testing is not available for all medications, and its integration into routine clinical practice is still evolving3.
Summary Table
| Aspect | Description |
|---|---|
| What is tested? | Genetic variants affecting drug metabolism and response |
| Sample type | Saliva, blood, or cheek swab |
| Purpose | Guide medication and dosage selection; reduce side effects |
| Clinical use | Before starting new meds, after adverse reactions, or lack of efficacy |
| Common drug classes tested | Antidepressants, antipsychotics, blood thinners, cancer drugs, HIV meds |
Pharmacogenomics testing represents a significant advance in personalized medicine, offering the potential for safer, more effective drug therapy tailored to each individual’s genetic profile125.
Citations:
- https://medlineplus.gov/lab-tests/pharmacogenetic-tests/
- https://my.clevelandclinic.org/health/articles/pharmacogenomics
- https://www.ncbi.nlm.nih.gov/books/NBK595332/
- https://www.mayo.edu/research/centers-programs/center-individualized-medicine/patient-care/pharmacogenomics
- https://www.genome.gov/about-genomics/educational-resources/fact-sheets/pharmacogenomics
- https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/pharmacogenetic-testing/
- https://kidshealth.org/en/parents/pharmacogenomics.html
- https://www.cdc.gov/genomics-and-health/pharmacogenomics/index.html
- https://genomind.com/solutions/pharmacogenetic-testing/
- https://med.stanford.edu/cvi/mission/news_center/articles_announcements/2021/the-problem-with-pharmacogenetic-testing.html
Answer from Perplexity: pplx.ai/share
Filed under: General Problems
I’m 75. Is there any hope for me to have enough pain control to have any quality of life before I die? My life has been destroyed by this inhumane experiment.