This is a review of ‘Personalized Pharmacogenomics: Predicting Efficacy and Adverse Drug Reactions’ in the Annual Review of Genomics and Human Genetics. This discusses medicine on an individual level and the role of genetics in prescribing drugs. There are many factors that need to be taken into consideration, as everyone is different and will therefore respond to drugs differently. When it comes to trying to cure or control a disease, it is not uncommon for clinicians to prescribe patients drugs. With that said, there are many risks involved. There is so much variability in drug response, and benefits versus risks are something clinicians need to carefully assess.
Pharmacogenetics is the study of genetic effects on an individual’s reaction to different drugs. The examination of a specific gene, or group of genes, may be used to foresee responses to a particular drug. Pharmacogenomics refers collectively to all the genes that impact gene responses, and how genome wide analysis may be used to pinpoint such genes in pursuit for novel drug targets and key determinates of drug reactions. The outcomes of a specific dose of a particular drug differ between different receivers. A drug that is successful in one person may have no effect in another person, while others may have limited responses or even sever adverse side effects. There are many contributive factors to such variation in drug response such as gender, age, body mass, diet, co-medication, disease states, environmental factors, and genetic factors. Drugs undertake the stages of absorption, distribution, target interaction, metabolism, and excretion. Genes that have an effect on any of these phases could influence the whole drug response.
There are two core sets of genes that are significant when looking at variation in drug responses. The first are those affecting the pharmacokinetic properties of drugs such as drug metabolizing enzymes and drug transports which influence how the drug is treated by the body. The second set of genes are those influencing pharmacodynamics properties of drugs including drug targets such as enzymes, receptors, and ion channels, as well as their allied pathway which govern how the drugs affect the body. Most of the genetic variance that effect drug action are called single-nucleotide polymorphisms, or SNPs. SNPs are frequently occurring single nucleotide substitutions of one base for another.
Two key aspects of drug response in relation to clinical significance are efficacy and toxicity. There is a lot of variation in drug efficacy. Efficacy refers to the greatest beneficial therapeutic reactions that a drug can create, and it is a gauge for clinical effectiveness. It can be conveyed in relations to a percentage of applicants who show a therapeutic response at a given standard dose. Toxicity refers to the extent to which a drug prompts undesirable or dangerous health effects that may be expressed with a percentage of patients who show adverse side effects at a given dose. The optimum dose range for a drug is that in which efficacy is highest and toxicity is lowest. In practice, achieving a conventional level of toxicity generally means efficacy is negotiated, and in some cases even the most harmless drugs can generate grave side effects. One of the main concerns lies within the group of extreme drug responders within a patient population. These include non-responders who ineffectively response to the drug, and adverse responders in which the drug produces risky side effects. If it was possible to recognize these individuals beforehand, actions in the form of treatments could be improved. The non-responders could receive an enlarged dose or a different medication, while the adverse responders could receive either a significantly reduced dose or a substitute form of medication.
Serious adverse drug reactions are critical in drug therapy because they cause undesirable reactions, hospital admittances, and even death. It is a very serious matter. For drug industries, adverse drug reactions are a major setback. For drug treatments, it is imperative to find ways in which to prevent or reverse these drug reactions, or to work around them based on the individual. Metabolism of the drug is an important aspect of what causes these drug reactions. One major difficulty is that the drugs are not disputed equally in everyone that takes a similar drug. Some medications are carried out by enzymes that only part of the population have in active form. The variability of these enzymes produces a lot of undesirable results in the patients because it is challenging to foresee the degree of elimination of the drug. Dosage is very diverse depending on the genetic profile of the patient. One main aspect is numerous people carry more than one active gene. Some metabolize the drug faster, while others do not. The other issue is that some individuals deprived of any operative enzymes can have reverse drug reactions because their body cannot remove the drug, therefore the concentration of the substrate will rise enormously when the drug is given at the standard dosage. Despite significant variability in ability to metabolize drugs, dosage drugs are typically done by population-based occurrence.
When it come to taking individual accounts into dosing drugs, it is important to keep in mind the persons genetics in coding the activity for the metabolizing enzyme. Those who rapidly metabolize the drug don’t get the appropriate effects, and therefore they usually have little to none response to the drug. Those who poorly metabolize the drug build up too much concentration of the substrate, which cause a higher risk of adverse drug reaction.
Individual dosing and personalized medicine is emerging quickly and has the capability to reduce drug adverse effects. This includes methods such as whole genomic analysis on each individual patient. This is a very specific test that looks at how drugs metabolize to the individual’s body.
When it comes down to it, the right medication can save a life. One drug that works for someone else may not work for another person. Because of genetic makeup, some people break down different medication either too slowly or too fast. Some people may be predisposed to threatening side effects from a drug simply by having the wrong genes. A genetic test can show how your body is likely to respond to these drugs beforehand.
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