Generic names for drugs should ideally

See Effective. Equally potent, or equally capable of producing a pharmacologic effect of a specified intensity. Obviously, if two drugs are not both capable of producing an effect of a given intensity, they cannot be compared with respect to potency; i. The Task Force recommended that an appropriate nomenclature should take into account three kinds of equivalence of drug preparations:. The fraction of C 0 remaining at some specified time after drug administration; more generally, the fraction of C, or A B , remaining after some specified time interval.

For first-order, single compartment systems i. The fraction of a dose which is absorbed and enters the systemic circulation following administration of a drug by any route other than the intravenous route; the availability of drug to tissues of the body, generally.

According to the law of mass action, the velocity of a chemical reaction is proportional to the product of the active masses concentrations of the reactants. In a monomolecular reaction, i. The minus sign indicates that the velocity decreases with the passage of time, as the concentration of unreacted substance decreases; a plot of C against time would yield a curve of progressively decreasing slope.

The mechanisms, the kinetics, described by the differential equation are termed first order kinetics because — although the exponent is not written — concentration C is raised to only the first power C 1. The units of k are independent of the units in which C is expressed; indeed, since a logarithm is dimensionless, and t has the dimension of time, the integrated equation balances, dimensionally, because k has the dimension of reciprocal time, t Then, substituting in the integrated equation above, ln 0.

Multiplying both sides of the equation by -1 yields 0. The existence of a monomolecular reaction can be established by plotting ln C, for unreacted material, against t and finding the relationship to be linear; the slope of the line is the original proportionality or velocity constant, and the intercept of the line with the ordinate is the natural logarithm of the original concentration of unreacted material.

Since natural logarithms have a fixed relationship to common logarithms, i. Such a pseudo-monomolecular reaction, because the velocity is determined by the concentration of only one of the two reactants, still follows first order kinetics.

Such eliminative processes mimic pseudo-monomolecular reactions, and the drug is eliminated from the body according to first order kinetics,.

The apparent velocity constant determined for such a process is called the elimination rate constant, k el , and the elimination half-life can be computed as 0. An agency of the Department of Health, and Human Services which is responsible for ensuring compliance with the amended federal Food, Drug and Cosmetic Act.

This agency must pass judgment on the safety of drugs, the labels affixed to drug packages, and all printed material accompanying a packaged drug before that drug may be introduced to interstate commerce. The law empowers the F. Prosecution of violation of the F. Drug formulations of identical composition with respect to the active ingredient, i.

Patent Office and identifies the special brand of the drug with the firm owning the name. FDA regulations require manufacturers of generic drugs to establish biological equivalence of their product to the original patented drug product. It is well recognized that a number of factors other than quantity of drug present in a dose can determine the ultimate therapeutic usefulness of the drug preparation, and even the availability of drug to the site of action once the preparation has been given.

Drugs may be generically equivalent but not therapeutically equivalent. Factors which affect therapeutic usefulness or efficacy of drug preparations include appearance, taste, disintegration and dissolution properties of the preparation, interaction of active materials with other ingredients including binders and solvents, pH, particle size, age of preparation, conditions of manufacture such as degree of tablet compression, and the nature and amount of coating of enteric-coated tablets.

When the patent of a proprietary drug expires, a manufacturer must establish the biological equivalence of its generic formulation in order to market the product. To do so, the bioavailability if the generic formulation is compared to the proprietary product in a cross-over experiment. Biopharmaceutics , U.

A condition characterized by a psychological craving for the effects produced by the administration of a drug. Its characteristics include: 1 a desire but not compulsion to continue taking the drug for the sense of improved well-being which it engenders; 2 little or no tendency to increase the dose; 3 some degree of psychic dependence on the effect of drug; but absence of physical dependence and hence of the abstinency syndrome; 4 detrimental effects, if any, primarily on the individual.

The period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. Half-lives can be computed and interpreted legitimately only when concentration or amount varies with time according to the law appropriate to the kinetics of a first order reaction: the common logarithm of the concentration or amount is related linearly to time, e.

The parameters of the equation can be estimated from the plot of experimental values of log C and t. The half-life can be computed simply by dividing the slope of the curve into 0.

The half-life of a drug in plasma or serum is frequently taken as indicating the persistence of the drug in its volume of distribution; this interpretation may be incorrect unless the material can move freely and rapidly from one fluid compartment of the body to another, and is not bound or stored in one or another tissue. The tissue for which the half-life of a drug is determined should always be specified, e.

Drug half-lives are frequently based on the results of chemical analyses, i. A drug molecule that leaves the plasma may have any of several fates: it can be destroyed in the blood; it can be eliminated from the body; or it can be translocated to a body fluid compartment other than the intravascular to be stored, biotransformed, or to exert its pharmacodynamic effects.

When the plot of log plasma or serum concentration during the period of its decline against time is composed of two straight line segments, the inference may be made that two first order processes are involved in the distribution and biotransformation and elimination of the drug. The earlier phase — represented by the line segment of greater slope — is termed the distributive phase, and corresponds to the period during which translocation of the drug to its ultimate volume of distribution occurs and is the dominant process; the later phase — represented by the line of lesser slope — is termed the eliminative phase, and corresponds to the period when biotransformation and elimination of drug are dominant processes.

For two-phase systems, three phase systems, etc. The effect of the law was to regulate possession and use of the materials designated as narcotics. Since regulation was achieved through taxation, the law was enforced by the Treasury Department, Bureau of Internal Revenue. Traffic in marihuana was first controlled by the Marijuana Tax Act of More recently, additional materials, e. The law is implemented by placing a nominal tax on certain materials under the law, and by requiring that physicians, dentists, etc.

Department of Justice. The potential for causing harm; that which is a potential cause of harm. Since the time of Paracelsus, in the early 16th century, it has been recognized that all chemicals, given in sufficient doses, are capable of producing harm.

Therefore, it is not very meaningful simply to call a chemical a hazard, or to speak of a chemical as hazardous, without qualification or definition. Three categories of information are needed to define a hazard: specific descriptions of the harms it can produce, specific identification of the species or kinds of subjects that can be harmed, and specification of the kinds of exposure to the chemical including dose which can result in the respective harms.

Observe that hazard is the potential for causing harm. However hazardous a chemical might be, it may present no risk if potential victims are not exposed to it! Risk management is the effort to limit the likelihood that the hazard of a chemical will be realized or manifested.

For chemicals, such as drugs, it is frequently more informative to consider their hazards relative to their potential for producing benefit, rather than relative to the hazards of other chemicals. An extremely potent therapeutic agent may also be potent in producing harm, but it may be a useful drug because of its large therapeutic index or standardized safety margin.

Hypersensitivity may exist but not be manifested until a second administration of hapten occurs. The dose of hapten or drug required to produce the allergic response may be smaller, larger, or the same size as the dose required for the drug to produce its characteristic pharmacologic effects ; hence hypersensitivity is not the same as sensitivity and the two words should not be used as synonyms. Sensitivity , Allergic Response , Idiosyncratic Response. A drug that produces a state clinically identical to sleep by means of action in the central nervous system.

A qualitatively abnormal or unusual response to a drug which is unique, or virtually so, to the individual who manifests the response. In other words, were frequency or intensity of idiosyncratic response used as a measure of effect in constructing a dose-effect curve, a curve might indeed be constructed, but its slope would be found to be 0 zero , indicating that effect was not significantly a function of dose.

In practice, the mechanism of production of an idiosyncratic response is unknown; once the mechanism is known, the response can usually be classified in some other way. Infusion, as a means of drug administration, involves an effectively continuous flow of a drug solution into the blood stream over a relatively long period of time. Intravascular injections are separate administrations of drug solutions, each over a short period of time.

A major purpose of an infusion is to maintain a steady blood or plasma concentration of drug over a long period of time, i. The concentration finally achieved varies directly with the infusion rate and indirectly with the total clearance of the drug always assuming first-order elimination and a single compartment system.

For a drug given by infusion, and eliminated by first-order kinetics from a one-compartment system, the rate at which C ss is achieved depends only on the half-life of the drug. In the absence of other doses such as a loading dose [q. The property of a drug that determines the amount of biological effect produced per unit of drug-receptor complex formed.

Two agents combining with equivalent sets of receptors may not produce equal degrees of effect even if both agents are given in maximally effective doses; the agents differ in their intrinsic activities and the one producing the greater maximum effect has the greater intrinsic activity. Meperidine and morphine presumably combine with the same receptors to produce analgesia, but regardless of dose, the maximum degree of analgesia produced by morphine is greater than that produced by meperidine; morphine has the greater intrinsic activity.

Intrinsic activity — like affinity — depends on the chemical natures of both the drug and the receptor, but intrinsic activity and affinity apparently can vary independently with changes in the drug molecule. Affinity , Receptors , Ceiling. Antagonism , Dose-Effect Curve. The rate of absorption of a drug absorbed from its site of application according to first-order kinetics.

The half-time for absorption is computed as 0. The period of time that must elapse between the time at which a dose of drug is applied to a biologic system and the time at which a specified pharmacologic effect is produced.

In general, the latent period varies inversely with dose; the relationship between dose and latent period for a given agent is described by a time-dose or time-concentration curve.

The loading dose is administered in order to achieve a therapeutic amount in the body more rapidly than would occur only by accumulation of the repeated smaller doses. The dose of a drug predicted by statistical techniques to produce a characteristic effect in 50 percent of the subjects to whom the dose is given.

The median effective dose usually abbreviated ED 50 is found by interpolation from a dose-effect curve. The ED 50 is the most frequently used standardized dose by means of which the potencies of drugs are compared. Although one can determine the dose of drug predicted to be effective in one percent ED 1 or 99 percent ED 99 of a population, the ED 50 can be determined more precisely than other similar values.

An ED 50 can be determined only from data involving all or none quantal response; for quantal response data, values for ED 0 and ED cannot be determined. In analogy to the median effective dose, the pharmacologist speaks of a median lethal dose LD 50 , a median anesthetic dose AD 50 , a median convulsive dose CD 50 , etc. Parameter , Bioassay , Dose-Effect Curve. The pharmacokinetic aspects of treatment schedules that involve more than one dose of a drug are discussed below.

The relationships described involve assumptions of instantaneous intravenous administration and distribution of a drug that is eliminated by first-order kinetics from a single-compartment system, and is given in equal doses at equal time intervals.

The relationships become less accurate in describing real situations to the extent that the real systems depart from the ideal model, i. When equal doses are administered at equal intervals, the peak plasma concentration after the nth dose, C max,n is given by the relationship:.

Knowing the half-life of a drug and the C ss,max and C ss,min desired to produce optimum therapy, the dose interval,? The doses to be administered at intervals,? The relationship among C ss,max , C ss,min and expected therapeutic outcome, including occurrence of side effects, are inferred from dose-effect relationships established in clinical pharmacologic experiments.

With repeated doses, at equal intervals, peak plasma concentrations C max approach but, in theory, never reach C ss,max. In practice, it is useful to know how long it takes for C max to reach some specified level with respect to C ss,max , i. Knowing the expected value of C ss,max and the fractional achievement desired, e. Then, knowing the dose interval,? The number of doses required to achieve the desired ratio of C max to C ss,max may be determined by dividing the right hand member of the equation by the length of the dose interval.

The number of doses in a series; as a subscript, the last dose in a series or the number of the last dose. C max , C ss , Multiple Dose Regimens. Formerly, an agent capable of producing coma or stupor from Greek narke: torpor, numbness. Now, usually, any drug which produces analgesia and is capable of producing stupor: pain is relieved by a dose or narcotic before the occurrence of sleep or unconsciousness.

Addiction , Anesthetic , Analgesic. A reference volume published formerly by the American Pharmaceutical Association containing standards of purity and methods of assay for some drugs, and formulae and methods of manufacture for a variety of pharmaceutical preparations.

Drugs were included on the basis of demand as well as therapeutic value. The N. A treatment incorporated into an experiment with the intention that it have no effects on the experimental system like those expected of the independent variable.

In a pharmacologic experiment, the negative control drug mimics in every way the drug preparation under investigation including identity of dosage form, vehicle, mode of application, etc.

The negative control drug has two functions in an experiment: 1. To permit ascribing a causal relationship between treatment with the independent variable and changes in the experimental system which follow treatment. If the experimental system responds to both the negative control drug and the drug preparation under test, one cannot — in the absence of other information — legitimately infer that the effects of the test preparation are caused by the supposedly pharmacodynamically active test preparation.

To serve as a basis for quantitative estimation of the effects of the independent variable in excess of those effects produced by non-specific changes in the environment or the experimental system. A test drug preparation may have non-specific effects like those of the negative control drug, but may also have specific effects that can be attributed to the ingredient that is unique to the test preparation. Careful use of a negative control drug in an experiment prevents erroneous conclusions about the apparent activity of a test preparation; use of a positive control drug prevents making erroneous conclusions about apparent inactivity of a test preparation.

One of the elements of an experiment which can be varied, but which the experimenter tries to control or maintain constant during the course of a specific experiment, while intentionally altering the independent variable and observing changes in the dependent variable. Parameters in one experiment stimulus strength, for example might well be independent variables in another. Terms of an equation that do not vary within the context of an experiment, but may be different under different circumstances.

Parameter should be distinguished from the independent and dependent variables. The science and study of the biological effects produced by chemical agents; more specifically, the science and study of how chemical agents produce their biological effects. In medical pharmacology, the science and study of how drugs produce their effects. Pharmacology , Pharmacokinetics , Therapeutics , Pharmacogenetics.

The science and study of the inheritance of characteristic patterns of interaction between chemicals drugs and organisms. Pharmacogenetics involves identification and description of such patterns, discriminating them from non-heritable patterns, and elucidation of the mechanism of inheritance. Pharmacogenetic studies illuminate many intraspecific and interspecific similarities, and differences in pharmacodynamic and pharmacokinetic mechanisms.

The science and study of the factors which determine the amount of chemical agents at their sites of biological effect at various times after the application of an agent or drug to biological systems.

Pharmakon — drug, and Logos — word is the study of drugs in all their aspects. Pharmacy, although often confused with pharmacology, is, in fact, an independent discipline concerned with the art and science of the preparation, compounding, and dispensing of drugs.

Pharmacognosy is a branch of pharmacy that deals with the identification and analysis of the plant and animal tissues from which drugs may be extracted. The pharmacodynamicist, or pharmacologist, identifies the effects produced by drugs, and determines the sites and mechanisms of their action in the body.

The pharmacologist studies the physiological or biochemical mechanisms by which drug actions are produced. The pharmacologist also investigates those factors that modify the effects of drugs, i. Pharmacotherapeutics is the study of the use of drugs in the diagnosis, prevention, and treatment of disease states. Toxicology is the study of drug effects that are inimical to health.

The toxicologist may investigate such diverse problems as the effects of overdoses of pharmacotherapeutic agents; the diagnosis, treatment, and prevention of lead poisoning in the paint manufacturing industry; the possibility that criminal poisoning was the cause of an otherwise inexplicable death, etc.

Pharmacology is a part of biology… Of all the vast number of pharmacologic reactions, those that the physician attempts to use for curative purposes are of the greatest interest and most deserved of study. Meter and R. Therapeutics , Pharmacodynamics , Pharmacokinetics , Pharmacogenetics , Toxicology. Latin: I will satisfy. A drug preparation incorporated into an experiment with the intention that it have effects on the experimental system qualitatively similar to those expected of the independent variable.

The positive control drug has two functions in an experiment: 1 to verify that the experimental system is indeed capable of undergoing the changes expected to follow manipulation of the independent variable.

If the system fails to respond to the positive control drug, its failure to respond to the independent variable is uninterpretable; 2 to serve as a basis for quantitative estimation of the relative efficacy of the independent variable. An expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect; an imprecise term that should always be further defined see EC 50 , ED A special case of synergy q.

For example, although physostigmine has no acetylcholine-like activity of its own, it potentiates the actions of acetylcholine by inhibiting the enzymes responsible for the destruction of acetylcholine. Intensity of effect may be potentiated , duration of effect may be prolonged: potentiation and prolongation are independent phenomena, but frequently occur together. A chemical with little or no pharmacologic activity that undergoes change in the body into a more active material.

The change may be a result of biotransformation, or may occur spontaneously, in the presence of, e. The square of the reciprocal of the index of precision is the measure of the amount of information that can be delivered by the system. Specifically, precision is computed in several steps. First, the deviation of each observed value of output from the corresponding predicted value is squared; predicted values are determined from the curve relating input and output for all the data.

Intrinsic Activity , Affinity , Antagonism. A drug, chemical, or dosage form, etc. Even physical systems of measurement are based on reference standards. The use of reference standards is of particularly great importance to the design and interpretation of biological experiments. In biological experiments, particularly, variability and instability of the biological test system can markedly influence the apparent effects and effectiveness of substances being tested.

The degree to which the input-output relationship is reproducible if the relationship is studied repeatedly under comparable conditions. For example, if a student took the same examination twice, or in two forms, would he get the same grade both times? If the same work were reviewed by two graders, would they both assign the same mark? The likelihood that harm will result from exposure to a hazard.

More generally, the probability that an event has occurred, or will occur, in members of a population under specified conditions, e.

Risk is calculated by dividing the number of subjects who experience an event by the number of subjects in the population at risk. The risk, so calculated, is one of the bases used to estimate the likelihood that the event will occur in the future, the predicted risk. Risk, calculated as described, also indicates the probability that any individual subject in the population at risk experienced the event.

For a meaningful estimate of risk following exposure of subjects to some hazard , it is necessary to have carefully defined the harm that was done, to have characterized the population at risk, and to have specified the conditions of exposure. The statistical techniques used to estimate risks and to compare them are, generally, the techniques used in epidemiology.

Perceived risk is the subjective assessment of the importance of a hazard to individuals or to groups of individuals, For example, hazards that affect children generally have higher perceived risks than those that tend to affect adults.

Hazards that produce fatalities grouped in time and space e. Perceived risks are not necessarily correlated with the risks, for the same hazards, measures by epidemiologic techniques. Risk management is the effort to reduce the likelihood that a hazard will produce harm. Risk management may involve decreasing the size of the population at risk e. The capacity or propensity of a drug to affect one cell population in preference to others, i.

Selectivity can be measured or described by means of such numbers as the Therapeutic Index, or the Standardized Safety Margin: not infrequently one wishes to express selectivity of drug action with respect to two potentially beneficial effects, or two potentially toxic doses, or two toxic doses, instead of one each.

Selectivity is generally a desirable property in a drug, e. Sometimes, selectivity of action is virtually precluded by the nature of the drug, e.

Sometimes selectivity of action for cells within an organism is not necessarily desirable, as in the case of certain economic poisons, i. They describe separate phenomena, each of which deserves an unambiguous name.

The ability of a population, an individual or a tissue, relative to the abilities of others, to respond in a qualitatively normal fashion to a particular drug dose. The smaller the dose required to produce an effect, the more sensitive is the responding system. Conversely, the drug would appear to be extraordinarily potent or impotent in such a patient. If a patient manifested an allergic response after raking aspirin, he would be considered hypersensitive to aspirin, regardless of whether the aspirin afforded him relief from pain, and regardless of the size of the dose required to elicit the allergic response.

Such a patient might be simultaneously hypersensitive to aspirin, and insensitive to aspirin, acting as an analgesic agent. Hypersensitivity is a property ascribed to a subject in a particular immunologic state. Drug effects which are not desirable or are not part of a therapeutic effect; effects other than those intended. For instance, in the treatment of peptic ulcer with atropine, dryness of the mouth is a side effect and decreased gastric secretion is the desired drug effect.

If the same drug were being used to inhibit salivation, dryness of the mouth would be the therapeutic effect and decreased gastric secretion would be a side effect. Pharmacological side effects are true drug effects. The existence of spare receptors reflects a circumstance in which the maximum effect produced by an agonist is limited by some factor other than the number of activated receptors.

Whether or not a system has spare receptors depends upon the nature of the receptor and its coupling to the measured response, the number of receptors, and the intrinsic activity of the agonist. The capacity of a drug to manifest only one kind of action. A drug of perfect specificity of action might increase, or decrease, a specific function of a given cell type, but it would not do both. Nicotine is not specific in its actions in autonomic ganglia; it both stimulates and depresses ganglionic function by a number of means.

Atropine is quite specific in only blocking the actions of acetylcholine at certain receptors; in general atropine does not stimulate cellular activity when it combines with receptors, nor does it block interaction with receptors of agonists other than acetylcholine. In affecting exocrine glands, acetylcholine itself is very specific, in that it causes only stimulation or secretion; acetylcholine, at the same time, is non-selective in its action, in that stimulation of all exocrine glands is produced by about the same dose of acetylcholine.

Selectivity is concerned with site of action ; specificity , with the kinds of action at a site. The therapeutic index q. Clinically, the standardized safety margin probably has greater practical meaning than does the therapeutic index, and, unlike the therapeutic index, the meaningfulness of the standardized safety margin does not depend on the parallelism of the dose effect curves from which the LD 1 and ED 99 are inferred.

The standardized safety margin more frequently than the therapeutic index can sometimes be computed from clinical data not involving lethal effects, e. See: Foster, R. An extreme and high degree of sensitivity to a drug or chemical.

Usually a high degree of sensitivity induced by some specific procedure such as denervation, administration of another drug, etc. Sensitivity to a drug, of some degree, is inherent in every organism; supersensitivity is a state that has had to be produced in the organism. In the supersensitive subject, the actions of the drug are qualitatively like those observed in a subject of normal sensitivity, and unlike those produced in a subject who is hypersensitive to the drug.

A mutually reinforcing drug interaction such that the joint effect of two drugs administered simultaneously is greater than the sum of their individual effects.

Synergism is distinguished from additivity , in which the joint effect of two drugs is equal to the sum of their individual effects. A point in time or a time interval; frequently a time interval following administration of a drug or the time interval between doses of a drug. Specific times of interest may be indicated by subscripts, e. The idea of half-life is legitimately applied only to the case of a drug eliminated from body fluid according to the laws of first-order reaction kinetics.

Half-Life , b , k el , First-Order Kinetics. A decline in the response to repeated applications of agonist, typically occurring over a relatively short time scale seconds to hours.

See also Desensitization , Tolerance. The therapeutic index is ordinarily calculated from data obtained from experiments with animals. As in comparing ED 50 s from two different drugs, the comparison of the LD 50 and ED 50 therapeutic index is most meaningful when the dose-effect curves from which the ED 50 and LD 50 are inferred are parallel.

The therapeutic index is a measure of drug selectivity, and analogous index numbers are frequently computed to measure selectivity that does not involve lethal effects.

For example, to measure the selectivity of a drug potentially useful in the treatment of epilepsy, the ED 50 for producing ataxia in mice might be compared to the ED 50 for abolishing electrically-induced convulsions in mice. The science and techniques of restoring patients to health. Properly, therapeutics has many branches, any or all of which may be needed in the treatment of a specific patient.

In addition to pharmacotherapeutics or drug therapy, there exist coordinate fields of therapeutics such as surgical therapy, psychotherapy, physical therapy, occupational therapy, dietotherapy, etc. Drugs are commonly considered capable of participating in one or more of the following general kinds of therapy:.

A single drug may have two or more therapeutic effects in the same patient at the same or different times, or in different patients. A dose of drug just sufficient to produce a pre-selected effect. Frequently, and improperly, restricted to the dose just sufficient to produce a minimal detectable effect. Median Effective Dose , Sensitivity , Potency. The graphical representation of the relationship — for a given drug and a given biological system — between concentration or dose and latency or latent period: the period of time elapsing between the time the dose is administered and the time a given effect is produced.

Time-concentration curves tend to be hyperbolic in form: as dose increases latency decreases and vice versa. Latency is an inverse function of concentration. But the hyperbolic relationship never approaches the axes as asymptotes; there is always a concentration below which the drug is ineffective, regardless of the duration of exposure of the tissue to the drug, and there is always a finite interval between the time of exposure to the drug and the time the response occurs.

The time-concentration curve is analogous to the strength-duration curve that the physiologist uses to determine rheobase and chronaxie. It is characteristic of true drug effects that a generally hyperbolic relationship exists between dose and latency. If, with increasing doses of material, a time-concentration curve and a dose-effect curve cannot be demonstrated, one cannot conclude that the material is responsible for the effects observed.

A condition characterized by a reduced effect of a drug upon repeated administration. In some cases, it may be necessary to increase the dose of the drug to attain the same effect, or the original level of effect may be unattainable. Tolerance typically develops over days to weeks, and is distinguished from tachyphylaxis , a more rapid decline in the effect of a drug. Tolerance can result from multiple mechanisms, including changes in drug metabolism and alteration in the number or responsiveness of receptors see desensitization.

A non-habitual drinker who is unaffected by several drinks of whisky downed in rapid succession is probably insensitive to alcohol rather than tolerant to its effects. Addiction , Sensitivity , Habituation , Dependence. Responses to drug that are harmful to the health or life of the individual. Toxic effects are not side-effects in the case of pesticides and chemical warfare agents.

Toxic effects may be idiosyncratic or allergic in nature, may be pharmacologic side effects, or may be an extension of therapeutic effect produced by overdosage. An example of the last of these is the apnea produced by an anesthetic agent. The scientific discipline concerned with understanding the mechanisms by which chemicals produce noxious effects on living tissues or organisms; the study of the conditions including dose under which exposure of living systems to chemicals is hazardous.

Hazard , Pharmacology , Toxic Effects. A simplified model of receptor activation by agonists. Agonists bind preferentially i. The United States Pharmacopoeia is a reference volume, published every five years by the U.

Pharmacopoeial Convention, which describes and defines approved therapeutic agents, as well as sets standards for purity, assay, etc. Agents are included on the basis of their therapeutic value. The U. The purposes of the Pharmacopoeia , as described in the Preface to the first edition in by Dr. Jacob Bigelow, are to :.

Using absolute dose to compute V d yields V d in units of volume, i. When the plot of log C against t yields a biphasic relationship a two compartment system , V d is computed by a different method, such as one based on the area under the C vs. Volume of Distribution , Compartment s. The degree to which output reflects what it purports to reflect, i.

The volume, in an organism, throughout which a drug appears to have been distributed; the volume into which a drug appears to have been dissolved after administration to an organism. Symbolized by V d. Suppose a drug has been completely absorbed from its site of application, has reached an equilibrium in its distribution among the several tissues of the body, and that no biotransformation or excretion of the drug has occurred. For this reason, and because clinical trials may exclude certain subgroups and high-risk patients, adverse effects may not be fully known until a drug has been in widespread clinical use for years see Drug Development Drug Development Promising compounds can be identified by mass screening of hundreds or thousands of molecules for biologic activity.

In other cases, knowledge of the specific molecular pathophysiology of various Whether a drug is indicated depends on the balance of its benefits and harms. In making such judgments, clinicians often consider factors that are somewhat subjective, such as personal experience, anecdotes, peer practices, and expert opinions.

The number needed to treat NNT is a less subjective accounting of the likely benefits of a drug or any other intervention. NNT is the number of patients who need to be treated for one patient to benefit. That means that of patients, 90 would live even without treatment, and thus would not benefit from the drug. Also, 5 of the patients will die even though they take the drug and thus also do not benefit.

Only 5 of the patients 1 in 20 benefit from taking the drug; thus, 20 need to be treated for 1 to benefit, and the NNT is NNT can be calculated for adverse effects also, in which case it is sometimes called the number needed to harm NNH. Importantly, NNT is based on changes in absolute risk; it cannot be calculated from changes in relative risk.

Relative risk is the proportional difference between two risk levels. In contrast, adverse effects are usually reported as absolute risk increases because they make a drug appear safer. For example, if a drug increases the incidence of bleeding from 0. Calculate the number needed to treat NNT based on absolute, rather than relative, changes in risks. For example, a drug that causes many more harms than benefits may be worth prescribing if those harms are minor eg, reversible, mild and the benefits are major eg, preventing mortality or morbidity.

In all cases, patient-oriented outcomes are best used. Genetic profiling is increasingly being used to identify subgroups of patients that are more susceptible to the benefits and adverse effects of some drugs.

For example, breast cancers can be analyzed for the HER2 genetic marker that predicts response to particular chemotherapy drugs. Genetic variations in various drug-metabolizing enzymes help predict how patients respond to drugs see Pharmacogenetics Pharmacogenetics Pharmacogenetics involves variations in drug response due to genetic makeup.

The activity of drug-metabolizing enzymes often varies widely among healthy people, making metabolism highly variable One goal in drug development is to have a large difference between the dose that is efficacious and the dose that causes adverse effects. A large difference is called a wide therapeutic index, therapeutic ratio, or therapeutic window.

For example, warfarin has a narrow therapeutic index and interacts with many drugs and foods. Insufficient anticoagulation increases the risk of complications resulting from the disorder being treated by anticoagulation eg, increased risk of stroke in atrial fibrillation , whereas excessive anticoagulation increases risk of bleeding. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world.

The Manual was first published in as a service to the community. Learn more about our commitment to Global Medical Knowledge. This site complies with the HONcode standard for trustworthy health information: verify here. Common Health Topics. Videos Figures Images Quizzes Symptoms.

Efficacy and Effectiveness. Patient-oriented outcomes Surrogate outcomes. Adverse Effects. Balancing Drug Benefits and Adverse Effects. Therapeutic index. Concepts in Pharmacotherapy. Test your knowledge. Which of the following is a type of drug-receptor protein that is located in cytoplasm and includes thyroid and steroid hormone receptors? More Content. Click here for Patient Education. Efficacy is the capacity to produce an effect eg, lower blood pressure.