Gene Research Changes: Understanding About Medicines

gene researchWe all appear to be similar but only morphologically. In fact, we are all unique with respect to our genetic constitution and thus possess a distinct physiological system which is different from any other member of the group.

We all have a special place in the environment that need to be recognized, identified, and analyzed for our existence. Nature plays a perfect role in terms of inheriting parental genes but these may vary in their outwardly expression depending upon the condition to which they are subjected. Thus, each one of us should be proud of our unique characteristics which must be respected while dealing with any manipulation of organ systems with various chemical and biological agents in an honest attempt to reduce the human sufferings. In other words, each human being should get personalized treatment for different diseases to suit his/her requirement based on his genetic code.

The treating physician puts his best efforts to treat his patient based on his knowledge, skills, and experience. However, he does not always succeed in achieving the goal, often perplexed by the therapeutic outcome. This could be a result of either medication error (which could have been avoided) or a genetic error which can significantly alter the response to the prescribed medicines. Clinical observations have revealed that individuals belonging to a particular region or race show more effect than desired to certain medicine whereas others show poor or no effect to the same medicine in same dose resulting in therapeutic failure. In addition, a small fraction may exhibit severe side effects or aggravation of the disease symptoms after taking the drug. This wide variation in drug effect calls for a scientific basis which as been explained on the basis of genetic defects among certain individuals. This has given rise to a new discipline called Pharmacogenomics: A branch of science that uses genetic/genomic information to better understand why people respond differently to drugs.

Considering the fact that every characteristic of the body is encoded by a specific gene, it is imperative to say that the cellular constitution and properties are a function of DNA sequence in the gene. Any change in the DNA sequence (inherited or acquired) shall result in a new type of cells with altered properties. This modified tissue/organ behaves in an unusual manner to the usual drug treatment. The science of genetics is not new, but has experienced a significant boost since the human genome project has been completed. Now is the time to capitalize on what basic science has provided and translate it into clinical practice. However, this can only happen if physicians and other health-care professionals, as well as patients, are being educated and become knowledgeable about pharmacogenomics. The need for public education in this field has never been more noticeable: recent reports about drug safety issues and the withdrawal of well-known drugs from the marketplace illustrate how important public awareness and knowledge in this field has become. These recent reports and the increased public awareness of drug safety, provide an unprecedented opportunity to alter dramatically the way modern medicine is performed. This impetus could provide the much needed and long anticipated start to integrate personalized (or targeted) medicine into everyday practice. Regulatory action can be taken at the level of providing information to physicians, patients, and other healthcare providers via drug labels (package inserts).

Pharmacogenomics can play an important role in identifying responders and nonresponders to medications, avoiding adverse events, and optimizing drug dose. Although scientists first noticed in the 1930s that natural genetic variations caused patients to respond differently to some medications, information about pharmacogenomics didn’t appear on a drug label until 2004. The first drug approved on the basis of ‘pharmacogenomic’ testing, Trastuzumab (Herceptin®), indicated for the treatment of breast cancer, is prescribed only if HER2/neu gene is over expressed in the tumor. In August 2007, the FDA added information to the widely prescribed blood thinner’s (warfarin) label saying that patients with variations in two different genes might need a lower dose. Other examples include: 6-mercaptopurine (6-MP), which is used to treat acute lymphoblastic leukemia in children. Based on a discussion of the FDA›s pediatric subcommittee, the 6-MP label has been updated from its original version and now states that ‹substantial dosage reductions may be required to avoid the development of life-threatening bone marrow suppression in these patients›. Another recent example is the label for Erlotinib (Tarceva®), indicated for the treatment of non-small-cell lung cancer. The label states an apparent larger survival effect in patients ith epidermal growth factor receptors (EGFR) whose density is determined by the presence of specific genes. The list of FDAapproved drugs with pharmacogenomicinformation in their labels is given at SFDA website

There are currently three categories of Pharmacogenomic information in drug labels according to the FDA:

  1. Tests required for prescribing
  2. Tests recommended when prescribing
  3. Pharmacogenomic information for information only

Pharmacogenomics has the overarching goal of developing safer, more effective drugs, and ensuring that patients receive the correct dose of the correct drug at the correct time. Some pharmacogenetic tests, primarily those related to drug metabolism have well-accepted mechanistic and clinical significance and are currently being integrated into drug development decision making and clinical practice. This fact is well illustrated by succinylcholine whose muscular paralysis action increases from few minutes to few hours due to lack of metabolizing enzyme (pseudocholinesterase) in the blood. This may result in respiratory paralysis and death. Antitubercular drug, isoniazid, leads to neuropathy in patients due to slow metabolism by acetylation. Antimalarial (primaquine and quinine) and antimicrobial drugs like ulphonamides and nitrofurantoin cause hemolytic anemia in patients with Glucose-6-phosphate reductase enzyme deficiency. All these toxic effects have been clearly assigned to genetic defects in certain individuals. The promise of pharmacogenomics lies in its potential to help identify sources of inter-individual variability in drug response (both effectiveness and toxicity); this information will make it possible to individualize therapy with the intent of maximizing effectiveness and minimizing risk. However, the field is currently in early developmental stages, and such promise has not yet been realized.

The reports clearly state that pharmacogenetic research deserves support from all concerned, but cautions not to create unrealistic expectations. This is one of the virtues that good educators must address: Pharmacogenomics will not replace, but enhance, existing good medical practice. A deliberate approach starts with educating young medical professionals by illustrating the benefits of pharmacogenomics and setting realistic expectations.

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