PHARMACOEPIDEMIOLOGY PHARMACOEPIDEMIOLOGY VS CLINICAL does not normally involve or require the mea PHARMACOLOGY surement of drug levels. However, pharmacoepi demology can be used to shed light on the Pharmacology is the study of the effects of drugs. pharmacokinetics of a drug, such as exploring Clinical pharmacology is the study of the effects whether aminophylline is more likely to cause e of drugs in humans (see also Chapter 4).Phar- nausea when administered to a patient simulta- macoepidemiology can be considered, therefore, neously taking cimetidine. However, this is a to fall within clinical pharmacology. In attempt- relatively unusual application of the field ing to optimize the use of drugs, one central Specifically, the field of pharmacoepidemiology principle of clinical pharmacology is that therapy has primarily concerned itself with the study of should be individualized, or tailored to the needs adverse drug effects. Adverse reactions have tra- of the specific patient at hand. This individuali- ditionally been separated into those which are zation of therapy requires the determination of a the result of an exaggerated but otherwise usual risk/benefit ratio specific to the patient at hand. pharmacological effect of the drug, so-called Doing so requires a prescriber to be aware of the Type A reactions, vs. those which are aberrant potential beneficial and harmful effects of the effects, so called Type B reactions. Type A reac- drug in question and to know how elements of tions tend to be common, dose-related, pre the patient' s clinical status might modify the dictable, and less serious. They can usually be probability of a good therapeutic outcome. For treated by simply reducing the dose of the drug example, consider a patient with a serious infec. They tend to occur in individuals who have one tion, serious liver impairment, and mild impair- of three characteristics. First, the individuals may ment of his or her renal function. In considering have received more of a drug than is customarily whether to use gentamicin to treat the infection, required. Second, they may have received a con it is not suficient to know that gentamicin has a ventional amount of the drug, but they may small probability of causing renal disease. A metabolize or excrete the drug unusually slowly, good clinician should realize that a patient who leading to drug levels that are too high. Third, has impaired liver function is at a greater risk of they may have normal drug levels, but for some suffering from this adverse effect than one with reason are overly sensitive to them. normal liver function. Pharmacoepidemiology In contrast, Type B reactions tend to be can be useful in providing information about the uncommon, not related to dose, unpredictable, beneficial and harmful effects of any drug, thus and potentially more serious. They usually permitting a better assessment of the risk/benefit require cessation of the drug. They may be due balance for the use of any particular drug in any to what are known as hypersensitivity reactions particular patient. or immunologic reactions. Alternatively, Type B Clinical pharmacology is traditionally divided reactions may be some other idiosyncratic reac- into two basic areas, pharmacokinetics and phar: tion to the drug, either due to some inherited macodynamics. Pharmacokinetics is the study of susceptibility(e.g glucose-6 hosphate dehy he relationship between the dose administered of drogenase deficiency) or due to some other a drug and the serum or blood level achieved. It mechanism. Regardless, Type B reactions are the deals with drug absorption, distribution, metabo- most difficult to predict or even detect, and major focus study of the relationship between drug level and- logic studies of adverse drug reactions drug effect. Together, these two fields allow one The usual approach to studying adverse drug to predict the effect one might observe in a reactions has been the collection of spontaneous patient from administering a certain drug regi- reports of drug-related morbidity or mortality men. Pharmacoepidemiology encompasses ele-(see Chapters 10 and 11). However, determining ments of both of these fields, exploring the effects causation in case reports of adverse reactions can achieved by administering a drug regimen. It be problematic(see Chapter 26), as can attempts 第170页第 170 页