Anusha Wei a/p Asohan
Universiti Sains Malaysia
Have you ever wondered why some medications work for you but don’t seem to help your friend? Let’s take high blood pressure as an example. The Norvasc that your doctor prescribed worked for you the first time you tried it. But your friend is still having a hard time finding the right medication that
works for her. Puzzling isn’t it?
Well, it’s not that simple. More often than not, it’s more complicated than any of us would like. There are several factors contributing to this situation of which include your age, sex, weight, diet, genetics, drug tolerance and many other factors that affect the outcome of the treatment. Out of the factors listed, would it surprise you to know that genetics plays a more significant role in your response to medication? The little blocks of information that make up your genes are responsible for the metabolism of drugs in your body.
There is a particular superfamily of enzymes known as the cytochrome P450 (CYP450) that is largely responsible for the metabolism of more than 90% of clinical drugs. Within this group of enzymes are many individual enzymes that metabolize these drugs either independently or cooperatively. The interaction of these CYP450 enzymes with medication will influence the efficacy of the drug and the possible side effects patients may experience. The types of alleles each patient have is an indicator of the kind of metabolizers the patients are. They can be classified as ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers and poor metabolizers depending on the allelic variants.
Now you may be wondering if medications can be personalized based on the individual’s genetic makeup. That would mean that doctors are able to prescribe specific medication including the optimum dosage that will give you the best result with little to no side effects. That scenario would be ideal. There are some type of diseases like colon cancer, acute lymphoblastic leukemia and other cancer types where individualized treatment is possible. Some of the known pharmacogenetic effects of drugs have been documented and these drugs are used in practice today. Two well established genes namely CYP3A4 and CYP2D6 are extensively studied for its function in different types of medications.
|Type of Medication||Purpose||Gene(s) Involved||Dosage/Drug Adjustment|
|Aripiprazole||To treat schizophrenia, autism and bipolar disorders||CYP3A4 and CYP2D6||Poor CYP2D6 metabolizers : ½ of the usual dose.
Poor CYP2D6 metabolizers and strong CYP3A4 inhibitors: ¼ of the usual dose.
|Codeine||To relieve mild to moderate pain (opioid)||CYP2D6||Poor CYP2D6 metabolizers and CYP2D ultrarapid metabolizers are to avoid the use of codeine and switch to a different drug because it may be ineffective and the side effects can be fatal.|
Aripiprazole and codeine are just some of the types of drugs that rely of pharmacogenetic testing prior to administration. There are currently more than 250 drugs that have their biomarkers identified and are known to be directly influenced by the genetic makeup of an individual. The knowledge of the enzyme activities of the said genes allows the adjustments for the medication.
As for other types of diseases and their respective treatments, a lot more research and progress remains to be carried out before it is accessible to the public. It may be a far stretch as of now but it’s definitely not impossible. Pharmacogenetic testing can potentially provide more accurate methods of drug selection and dosage administration and reduce the risk of patients experiencing unwanted and harmful side effects.
Pharmacogenetics is especially important where adverse drug reaction (ADR) may occur. ADR is a result of the idiosyncratic effects of drugs when they are metabolized by the body. Based on statistics by the FDA, ADR is the fourth leading cause of death in the US, with approximately 100,000 deaths yearly. With pharmacogenetics, ADRs can be prevented as proper treatments can be administered.
Although promising, there are a lot more variables involved in the application of pharmacogenetics in the medical field. The study of single nucleotide polymorphisms (SNPs) that are responsible for diseases is complex and requires extensive research to identify and match genes to drug responses. This process can take a long time before they are properly documented. Nonetheless, it’s definitely exciting to see what great heights pharmacogenetics can bring us to.