Pharmacotherapy is the use of medicine in the treatment of diseases, conditions, and symptoms.
History of pharmacotherapy
Pharmacotherapy is not a contemporary science. The use of drugs to treat illness is a practice that has been accepted for thousands of years. A famous example is Hippocrates, who is generally credited with revolutionizing medicine in ancient Greece by using beneficial drugs to heal illness. Traditionally, plants have been the source of medicinal drugs, but modern day medicine in the United States mostly utilizes synthesized or purified bioactive compounds, rather than an entire sample of plant matter. The advantage to this method of pharmacotherapy is that the dose of medicine rendered is standardized and pure, rather than an unknown drug dosage administered in addition to a wide variety of other chemicals present in the plant. Modern pharmacotherapy is the most common course of treatment for illness in the United States.
Pharmacokinetics and pharmacodynamics
Pharmacokinetics is the study of the concentration of a drug and its metabolites in the body over time. A drug that remains in the body for a longer time period will require lower subsequent doses to maintain a specific concentration. How quickly a drug clears from the body is a function of its absorption, bioavailability, distribution, metabolism, and excretion properties.
The absorption of a drug is the rate at which it leaves its site of administration. The bioavailability of a drug describes the extent to which it is available at the site of action in a bioactive metabolic form. A drug absorbed from the stomach and intestine passes through the liver before reaching the systemic circulation. If the liver biotransforms the drug extensively into an inactive form, its availability in bioactive form would be greatly reduced before it reaches its site of action. This is known as the first pass effect. Sometimes the liver biotransforms an inactive drug into an active form.
Which parts of the body drugs distribute to affects the length of time the drugs remain in the body. Fat-soluble drugs may deposit in fat reservoirs and remain in the body longer than drugs that are not fat-soluble. Drugs are metabolized within cells, often into inactive forms. The rate at which a drug is excreted from the body also affects its pharmacokinetics. Pharmacokinetic information about a drug allows the determination of an optimal dosage regimen and form of administration that will produce a specified drug concentration in the body for a desired period of time.
While pharmacokinetics is the study of drug concentration versus time, pharmacodynamics is the study of drug effect versus concentration, or what effect a drug has on the body. Pharmacodynamics measures a quantifiable drug-induced change in a biochemical or physiological parameter. Pharmacodynamics is the study of the mechanism of action of a drug. Medicinal drugs have targets to reach at the site of action. These targets are usually a specific type of drug receptor. Drug and drug receptor interactions can be measured. Complex pharmacodynamic equations combine with measurable pharmacokinetic values to determine the overall effect of a drug on the body over time.
Pharmacogenetics and pharmacogenomics
Pharmacogenetics is the study of the extent to which genetic differences influence the response of an individual to a medication. This science is still at an early stage in its development, but its importance is well understood. While drug treatment remains the cornerstone of modern medicine, in some cases it has adverse side effects or no effect at all. Adverse drug reactions are a leading cause of disease and death. It has been known for some time that genetic variation often causes these unanticipated situations.
While pharmacogenetics is the term used to describe the relationship between a genetically determined variability and the metabolism of drugs, pharmacogenomics is a separate and much more recent term that expands the concept. Pharmacogenomics includes the identification of all genetic variations that influence the efficacy and toxicity of drugs, describing the junction of pharmaceutical science with knowledge of genes. Pharmacogenomics is the application of the concept of genetic variation to the whole genome. Pharmacogenomics takes the concept of pharmacogenetics to the level of tailoring drug prescriptions to individual genotypes. There is an emerging trend towards defining both terms as pharmacogenomics.
There are many worrisome issues associated with modern pharmacotherapy that necessitate the study of pharmacogenomics. The optimal dose for many drugs is known to vary among individuals. The daily dose for the drug propranolol varies 40-fold and the dose for warfarin can vary by 20-fold between individuals. Also, the same drug does not always work in every patient. Thirty percent of schizophrenics do not respond to antipsychotic treatment. A major concern is adverse drug reactions. In the United States, adverse effects are a major cause of death. Research has demonstrated that gene polymorphisms influence drug effectiveness and toxicity, leading to these inconsistencies in patient response, affecting all fields of pharmacotherapy. Some drugs are known to produce potentially fatal side reactions at therapeutically effective doses. The current accepted method of addressing this situation involves determining the correct concentration of the drug for the patient so that therapy can be ceased before potentially irreversible damage. At best this is complicated, time-consuming, and expensive. It is also potentially dangerous for the patient.
The goal of pharmacogenomics is to maximize beneficial drug responses while minimizing adverse effects for individuals. In the future, pharmacogenomics may hold the promise of personalized drugs. However, genetic variation is not solely responsible for variable drug response. Other factors such as health, diet, and drug combinations are all very relevant.
Pharmacoepidemiology and pharmacoeconomics
Epidemiology is the study of the distribution and determinants of disease in large populations. Epidemiology has a precise and strict methodology for the study of disease. Pharmacoepidemiology is the application of epidemiology to the study of the effects of drugs in large numbers of people. The discipline of pharmacoepidemiology maintains a close watch on the therapeutic drugs commonly used in society. If the drug monitoring and reviewing process is not implemented, potential adverse effects of drugs and their misuse could have seriously deleterious effects on the population.
Pharmacoepidemiological studies performed on a population seek to address many different issues. Studies are performed to identify and quantify adverse drug effects, including delayed adverse effects. This is where most research in pharmacoepidemiology has focused. Analyses evaluate the efficiency and toxicity of drugs in specific patient groups such as pregnant and lactating women. Studies are performed on unanticipated side effects of drugs, along with anticipated side effects to monitor their severity. Research is done on the expected beneficial effects of drugs to verify their efficacy. Also, unanticipated beneficial effects of some drugs are examined. Factors that may affect drug therapy are studied to draw correlations between them and effects on pharmacotherapy. Such factors include sudden changes in drug regimen, age, sex, diet, patient compliance, other diseases, concurrent recreational drug usage, and genetics.
Pharmacoepidemiology can be used in conjunction with pharmacogenomics to examine how genetic patterns present in a population may affect a society's use of a specific therapeutic, or the need for gene-specific pharmacogenomic studies in a population. Studies are performed to examine a few candidate genes where genetic variability has been shown to have biological consequences. Sub-sequent research attempts to correlate phenotypic markers with genetic characteristics by association studies, involving the analysis of either a specific drug response as a continuous trait or of separate groups (drug responders versus drug non-responders). These genetic association studies are complex and depend on the frequency of the trait, frequency of the genetic variation within the population, the number of contributing genes, and the relative risk associated with the genetic variation. Reviews of drug utilization are generally done on overuse of drugs or use of costly drugs. Expensive drugs may be reviewed in a cost-benefit analysis involving pharmacoeconomics.
Pharmacoeconomics has a close relationship to the discipline of pharmacoepidemiology. Analysis of cost effectiveness, cost benefit, and cost utility are incorporated in pharmacoepidemiological research. A related topic of controversy is the validity of using economic analysis of pharmaceuticals as a proxy for prescribing medication, or a reason for prescribing one medication over another. The influence of pharmacoeconomic data on the choice of medication prescribed may be considerable. A general concern is whether a physician has the best interest of the patient in mind or of economics when choosing a medication. While the two concerns are not necessarily in contradiction, they sometimes may be. These topics are also being explored in prescribing research.
Goodman Gilman, Alfred, Joel G. Hardman, Lee E. Limbird, Perry B. Molinoff, and Raymond W. Ruddon, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill Health Professions Division, 1996.
Thomas, Clayton L., ed. Taber's Cyclopedic Medical Dictionary. Philadelphia: F. A. Davis Company, 1993.
Pharmacogenetics and Pharmacogenomics Knowledge Base. <http://pharmgkb.org/index.jsp> (May 23, 2004).
Maria Basile, PhD