If a particular drug is prescribed to a group of people, different people will have different reactions and side effects from the drug. The reactions that we get from taking a specific medicine can be attributed to our inherited genes. That said, when it comes to medications, the individual response from the body and our unique genes may mean that a drug may be effective for one individual while being ineffective for another. Likewise, a medicine that does not harm one individual may harm another even when the dosage administered is the same.
Most of the drugs we consume are usually metabolized (chemically broken down) by different enzymes found within the human body. In some instances, the chemicals that are active in a drug can be made dormant through metabolism. In other instances, a drug's inactive or dormant chemical components can be made more active once the enzymes break down the drug in the body. When it comes to ascertaining that medication effectively serves its purpose once consumed, the challenge is usually in making sure that the active part of the medication remains in the system just long enough for it to effectively serve its intended purpose. However, each individual's enzymes responsible for metabolizing drugs react differently, either too fast or too slowly. When enzymes react too fast, the medication that a person has taken may pass through the body too quickly and fail to serve its intended purpose. On the other hand, if enzymes react too slowly, the medication may stay too long in the system and end up producing unintended side effects.
The unique responses elicited by an individual to a drug can also be attributed to the variability in the compounds being targeted by a drug. A good example is a specific protein that a drug binds with in order to produce its desired effect. Sometimes, after taking certain medications, a person may also display specific side effects (hypersensitivity reactions) because there is a variation in the proteins that produce an immune response in the body.
With that in mind, we can now explore pharmacogenetics in detail
So, what exactly is pharmacogenetics?
Pharmacogenetics is the study of the variations in the human genetic sequence that causes individuals to react differently to medications. After analyzing the genes that produce drug binders or the enzymes that break down a drug/are responsible for eliciting an immune response from the body, a doctor can either alter the dosage they are giving to an individual or even change the drug that they are prescribing entirely. When choosing the type of medication to prescribe to an individual, doctors also consider other medications being taken by the individual at that given time with a view of avoiding negative drug-drug interactions.
Sometimes, you may find the term pharmacogenomics being used in place of the term pharmacogenetics. These two terms share an almost similar meaning, so much so that there is no exact/actual differentiation in the meanings of both terms. However, generally speaking, pharmacogenomics refers to the study of the different genes that help induce an effect from a drug once it is consumed. On the other hand, pharmacogenetics refers to the study of the variations in genes that affects how a drug is metabolized and how that affects an individual's reaction to a medication. We shall only use one term throughout the discussion below pharmacogenetics to avoid confusion and enhance clarity in this article.
FAQs On Pharmacogenetics
1. What Is the Importance of Pharmacogenetics?
There are several types of drugs that can be used to treat a specific medical ailment. When choosing a drug regimen for a sick individual, doctors typically tend to choose just one drug out of several to treat the condition in question. The ideal dosage and the times to take the drug are usually calculated based on the expected drug metabolism rate and clearance rate from an average person's body. Each individual's standard dosage and timing also consider other factors such as weight, age, and sex. However, clinically speaking, each individual usually elicits unique responses from their medications, which means that doctors must adjust each regimen they prescribe to suit each individual. For example, if a person is taking medication that produces adverse side effects, the doctor may choose to prescribe another type of medication. The doctor can also alter the dosage given to an individual (either increase or decrease it) depending on how they respond to the current dosage. In some instances, you can also find that an individual responds positively to a specific medication. Still, once another drug is introduced into their regimen, they may start exhibiting new side effects.
A drug's effects on an individual are usually monitored through blood tests, and based on the test results; the doctor can choose to maintain, increase, or decrease the current dosage in an established therapeutic range. If the doctor changes the dosage that an individual is taking, they usually monitor any new effects in a process known as therapeutic drug monitoring. If the changes that have been made to the drug dosage one is taking do not elicit any positive results, then the doctor may choose to prescribe an alternative drug.
Pharmacogenetics's most important role is that it allows health practitioners to prescribe medications for individuals based on their unique genetic sequences. One of the key reasons pharmacogenetics is becoming highly popular is that it will enable doctors to understand how an individual is likely to react to their medications. The data gained through pharmacogenetics can help doctors determine the most appropriate medications for a patient while also helping the patient understand the drug dosages they should take. Pharmacogenetics is already assisting the patients to predetermine the medications and dosages that are likely to be most effective for a patient while lowering the risk of any adverse side effects occurring.
2. How Do Genes Vary & How Does Pharmacogenetic Testing Work?
Genes are the smallest units of genetic material in the human body. They are the segments of DNA that usually code the body to produce specific proteins, including the proteins used during metabolism (enzymes). In most cases, a human being usually has two copies of a gene; one is generally inherited from the father while the other is inherited from the mother. Each gene is usually composed of a unique and specific code. The code in the genes is a sequence of nucleotides (A, T, G, or C). Among the general population, one of the four nucleotides found in the gene is the most predominant. This predominant nucleotide is usually known as the wild type. If a person has a nucleotide that varies from the wild-type nucleotide in one copy of their genes, that person usually has a heterozygous nucleotide variant. If a person has a heterozygous nucleotide in both copies of their genes, they are generally said to have a homozygous nucleotide variant.
Nucleotides or genetic variants (also called mutations or polymorphisms) usually occur throughout the population. Some genetic mutations do not usually have any known harmful effect within the body, but they may affect features such as hair and eye color, and height. However, there are other genetic variations that may cause specific ailments. There are also different genetic variations that may have an impact on how a person responds to medications.
Pharmacogenetic tests are usually done to identify the genetic variants that may affect how a person responds to certain types of medication. The variants that affect a person's response to medication typically occur in genes that code the production of enzymes used to metabolize drugs, drug targets (binders), or the proteins that induce an immune response from the body. Pharmacogenetic tests can be used to determine if an individual has heterozygous or homozygous genetic mutations that can impact how one's response to medications.
3. When Are Pharmacogenetic Tests Ordered?
A doctor can order pharmacogenetic tests to identify if any genetic variations are known to affect how an individual responds to medication at any point during the treatment process. This means that the tests can be done before treatment commences, as the treatment progresses, or later on during the treatment process. To identify and tailor the most appropriate drug therapy for a patient, the doctor can combine the results of pharmacogenetic tests with the patient's other medical data, which may include their:
- Age
- Health
- Weight
- Any medication they are currently taking
In some cases, the doctor may rely on the results of pharmacogenetic tests to change the drug doses proffered to a patient or change the type of medication being prescribed to the patient. Pharmacogenetic tests usually provide the doctor with additional information necessary for crafting the best drug therapy for a patient, but it does not always necessarily replace therapeutic drug monitoring.
Health practitioners usually carry out pharmacogenetic tests on a specific gene in a patient only once. Repeat tests of a particular gene are not typically necessary since a person's genetic makeup does not change over time. Depending on the type of medication being prescribed to a patient, the doctor may order that either one or both genes are tested. One type of medication that usually requires multiple pharmacogenetic tests is the drug Warfarin. Multiple tests are necessary for this medication since it can be affected by genetic mutations in CYP2C9 and VKORC1.
The doctor may also order pharmacogenetic tests before a patient starts a specific drug therapy. Additionally, tests can be ordered if a patient begins experiencing adverse side effects on consuming a drug or is unable to maintain a stable dose of a medicine. Sometimes, a patient may not experience any adverse side effects until they start taking (or stop taking) other drugs that affect the metabolism of their current medication.
4. What Are Some of The Pharmacogenetic Tests That Can Be Carried Out?
At this point, pharmacogenetic tests can only be carried out for a limited number of drugs. Additionally, some tests can only be carried out within specific ethnic groups. Below, we will list some of the medications for which pharmacogenetic testing can be carried out, the gene tested, and the medical condition for which the drug is administered.
- Methylphenidate gene tested is DRD4, a drug is administered for attention deficit disorder.
- The test of Azathioprine, mercaptopurine, thioguanine gene is TPMT; the drug is administered for autoimmune disorders and childhood leukemia.
- Irinotecan gene tested is UGT1A1, the drug is administered for cancer.
- 5-fluorouracil genes tested are DYPD variants and TYMS gene mutations; the drug is administered for cancer.
- Clopidogrel (see clopidogrel CYP2C19 genotyping gene tested is CYP2C19, drug is administered for cardiovascular ailments.
- Selective serotonin inhibitors (SSRIs) gene tested is 5-HTT, the drug is administered for depression.
- Carbamazepine, phenytoin gene tested is HLA-B*1502, the drug is administered for epilepsy.
- Warfarin (see warfarin sensitivity testing genes tested are VKORC1 and CYP2C9, the drug is administered for excessive clotting disorders.
- Some statins (for example, simvastatin) gene tested is SLCO1B1, a drug is administered for high cholesterol.
- Abacavir gene tested is HLA-B*5701, the drug is administered for HIV.
- Opioids gene tested is OPRM1, the drug is administered for pain management.
- Antipsychotics (for example, mephobarbital, haloperidol, thioridazine) genes tested are DRD3, CYP2D6, CYP2C19, CYP1A2, the drug is administered for psychiatric treatment.
- Some antidepressants and antiepileptics (for example, phenytoin, carbamazepine, valproic acid, phenobarbital) genes tested are CYP2D6, CYP2C9, CYP2C19, CYP1A2, SLC6A4, HTR2A/C, the drug is administered for psychiatric treatment and epilepsy.
5. Can Anyone Undertake Pharmacogenetic Tests?
Currently, the only people who can undergo these tests are those who are now taking or are planning to take a drug with a pharmacogenetic test.
6. Do I Need to Take a Pharmacogenetic Test Before Taking Certain Medications?
No. However, the FDA may recommend a test, as is the case for the drug Irinotecan; however, it is not an absolute necessity.
7. Why Did I Receive a Pharmacogenetic Test Only Once?
Sometimes, you are only tested once because your genetic makeup does not change with time. However, should you start taking another medication that has a pharmacogenetic test associated with it, your doctor may order more tests.
8. Do I Still Need to Have My Drug Responses Monitored After Undergoing a Pharmacogenetic Test?
Since other factors may affect your response to medication apart from genetics, your doctor may still carry out therapeutic drug monitoring even after you have been tested.
9. What Type of Sample Is Required for a Pharmacogenetic Test to Be Carried Out?
To perform the test, your doctor will collect a blood sample by inserting a needle into a vein in one of your arms. Other samples that can be used for testing include buccal swabs and saliva samples which can be collected by swabbing the inner side of your cheek.
10. What Is the Difference Between Pharmacogenetic Tests and Genetic Tests?
Pharmacogenetic tests are usually done with a view of determining how a person will likely react to a certain medication. On the other hand, genetic tests are generally done to predict the potential development of a genetic disease for use in forensic medicine or when trying to establish parentage. Genetic testing is also applied when doctors are trying to detect the genetic material of viruses and bacteria (DNA or RNA) in order to help diagnose an infection.
11. Will I Be Put Through Other Evaluations After Taking a Pharmacogenetic Test?
Your doctor may carry out different types of evaluations depending on the results of your tests. You may be monitored differently, especially if you are:
- About to start taking a drug
- Changing your daily dosage
- Adding a new medication to your drug therapy
- Discontinuing an existing medication from your therapy
12. Should My Family Members Also Receive Pharmacogenetic Tests?
This is a question that you should pose to your doctor. In some cases, it may be helpful for family members to go through the test. Note that this test will only be relevant for your members if they are about to start taking the same medication that you are taking or another type of drug in the same classification. If your family members have ever received pharmacogenetic testing, they should share it with your doctor along with any other pertinent details in the family's medical history.
13. How Do I Know If I Need or Do Not Need a Pharmacogenetic Test?
To identify if a pharmacogenetic test will help, you and your doctor should consider your ailment, the side effects you have developed after taking medications in the past, the available drugs, and why you may need the test. Remember that pharmacogenetic tests are not usually applied alone when choosing the best treatment; instead, they typically provide your doctor with additional information to be used in addition to any other clinical diagnosis that has already been made.
