Genetics – Pharmacogenomics

Approximately 40% of current prescription medication including all psychotropic drugs are metabolised by chemicals in the CYP450 enzymes genes in your liver.  This data can be found in scientific terminology contained in the Product Information (PI).
For more information about available testing in Australia www.genesfx.com
There are 4 distinct test results for most of the CYP450 genes.

1. The Poor Metaboliser (PM)
2. The Intermediate Metaboliser (IM)
3. The Extensive Metaboliser (EM)
4. The Ultrarapid Metaboliser (UM)

1. Poor metabolisers: These have 2 non-functional genes and so drugs are metabolised more slowly.This makes them more prone to side effects. A lower dosage of the drug is usually required or an alternative drug be given instead because the blood levels may become higher due to the slow elimination of the drug.
2. Intermediate metabolisers: This category refers to individuals who metabolise drugs a little slower than normal and may require dosage adjustments.  The cause is either due to the presence of one normal gene which produces enzyme normally and one completely non-functioning gene or the presence of 2 genes that produce enzyme with subnormal activity.  Alternative drugs or reduced dosages should be tried.

1. Extensive metabolisers (normal): They have 2 normal genes and metabolise medications at the normal rate and so should take the standard recommended dosage. This finding is NORMAL.
2. Ultrarapid metabolisers: They have more than 2 functional copies of the gene and (up to 13 copies have been reported).  Or a change in the gene that makes the more enzyme than normal.They metabolise very rapidly so they may get little or no benefit of the drug unless they are given a higher dosage

Warning:  Drug-Drug interactions can results in severe adverse reactions, many drugs and other products such as cold and flu treatments can interact and inhibit your genes placing you at risk of experiencing an Adverse Drug Reaction.  If you have selected this type of drug treatment we urge you to know your drug and understand the limitations, these drugs can be very unstable and the risks can result in serious injury and provoke suicidal ideation.

Please find a chart below which shows the correlation of genetic findings for each genotype of the genes CYP4502D6.

Click to enlarge

The report titled Improving the Quality Use of Medicines in Australia completed by Deloitte Economics in collaboration with Dr Stan Goldstein and Mr Malcolm Crompton of Integrated Information Solutions, outlined the importance of pharmacogenomics and more alarming the cost to the Australian Taxpayers.  It was reported that our government spends 1.6 Billion a year caring for patients who are genetically predisposed to the risks and inefficiency of drugs that use these pathways and that are not pre tested to determine the risks or benefit of such therapy.

It is important to understand that increased side effects are not only caused by variations in drug metabolism genes. They can also arise from drug-drug interactions, variations in drug target (rather than metabolism) genes, human error, and factors such as age, gender, overall health, hormones, concurrent disease, and diet.

If your doctor prescribes you or your child a drug metabolised via these genes, without evidence of your genotype, they are at best “guessing” the benefit.  Without a solid understanding of the variants such as, drug-drug interactions they are unqualified to predict the outcome.  You need to encourage your doctor to order a DNAdose to ensure they have all the evidence to support an accurate and safe treatment plan.

We encourage you to sign our petition to urge the government to provide funding via Medicare for genotype testing.  All Australians should be entitled to be testing prior to experimenting with drugs that they may not even be able to metabolise, not just the Australians who can afford it.

More information on some of the types of drugs that use the CYP450 genes.

Substrates
Below is a list of drugs (substrates) that are metabolised by specific CYP450 enzymes.  

Inhibitors
Inhibitors bind to the enzyme and reduce the enzyme activity in metabolising the substrate (drug). A strong inhibitor greatly decreases the amount of drug metabolised. This may lead to an increase in side effects for active drugs and a decrease in effect for pro-drugs. Weak inhibitors have a minimal effect on this process; therefore they are not included in the list below.

Strong and moderate inhibitors are listed below according to the specific enzyme they inhibit:  

Inducers
Inducers stimulate the production of an enzyme which increases the rate of metabolism of a drug.  Examples of enzyme inducers are listed below:

This information is not intended to be a substitute for medical advice.