Which action could make a drug more potent?

Professor emeritus and former president of Pharmacology at Boston University School of Medicine A — B — C — D — E — F — G — H — I — K — L — M — N — P — R — S — T — U — V — Z The use of the word “accurate”, error-free, when referring to scientific observation or scientific method sometimes hides the fact that even the best methods and observations are relatively error-free. The use of the single word “accurate” also hides the fact that a number of independent elements contribute to the general absence of errors.

Which action could make a drug more potent?

Professor emeritus and former president of Pharmacology at Boston University School of Medicine A — B — C — D — E — F — G — H — I — K — L — M — N — P — R — S — T — U — V — Z The use of the word “accurate”, error-free, when referring to scientific observation or scientific method sometimes hides the fact that even the best methods and observations are relatively error-free. The use of the single word “accurate” also hides the fact that a number of independent elements contribute to the general absence of errors. The effective use of a method or observation requires that we know the ways and the degrees to which the data are error-free, not that we only know that the data is “accurate” or “inaccurate”. The elements that must be considered in a comprehensive evaluation of a method or system can be derived from the properties of the quantitative relationship between the “input” and the “output” of the system.

The input-output relationship, despite its generality, has a specific application, and specific names, in different scientific fields and for different types of experimental or observational systems. In physics and engineering, the “stress-strain diagram” is a special representation of the input-output relationship; in pharmacology, the “dose-effect curve” is an example of the input-output relationship. In quantitative chemical analysis, the “calibration curve” is an example of the relationship between input and output. In general, the “input” can be viewed as the measured value of an independent variable or “measure”; the output can be viewed as a measurement performed under non-standard or test conditions.

A ligand that binds to a receptor and alters the state of the receptor, resulting in a biological response. A partial agonist is an agonist that produces a maximal response that is lower than the maximum response produced by another agonist that acts on the same receptors in the same tissue, as a result of lower intrinsic activity. A full agonist is an agonist that produces the greatest maximal response of any known agonist acting on the same receptor. An inverse agonist is a ligand that, by binding to a receptor, reduces the fraction of receptors in an active conformation, thus reducing basal activity.

This can occur if some of the receptors are in the active form in the absence of a conventional agonist. Some drugs may act as haptens or allergens in susceptible individuals; re-administering the hapten to that individual produces an allergic response that may be severe enough to attract the patient's or physician's attention. The response may be so severe as to endanger the patient's life. The symptomatology of the allergic response is the result of a complex mechanism that is only “activated” by the hapten.

Therefore, allergic responses to different haptens are fundamentally the same and qualitatively different from the pharmacological effects that haptens manifest in normal subjects, that is,. The dose-effect curves obtained after administration of the antigen to sensitized subjects generally reflect the dose-effect curves of the products of the allergic reaction, although the severity of the effects measured is proportional to the amount of antigen administered. The positive identification of a response as being allergic in nature depends on the demonstration of an antigen-antibody reaction underlying the response. In the case of specific patients, a presumptive diagnosis of an allergic response must sometimes be made, since there is no opportunity to formally identify an antigen-antibody reaction; such diagnoses can be made and justified, since the clinical symptomatology of allergic responses is usually characteristic and clear.

Obviously, not all adverse drug effects are allergic in nature. The amount of change in the output measured per unit of change in the input. The slope of the input-output or dose-effect curve. Engineers sometimes call “amplification” “sensitivity”.

It differs from an anesthetic agent in that it relieves pain without loss of consciousness. Synergy, enhancement, intrinsic activity, affinity, body weight. Sometimes, as a subscript, it indicates “from” or “inside” the body; therefore, A B is the amount of drug in the body. The slope of a linear graph of C (not the logarithm of C) against t; the slope of the line graph of a zero-order reaction, in which equal amounts of chemical substance react at equal intervals of time.

Positive control drug, negative control drug, dose-effect curve, time-concentration curve The percentage of the dose that enters the systemic circulation after administration of a given dosage form. More explicitly, the relationship between the amount of drug “absorbed from a test formulation” and the amount “absorbed” after administration of a standard formulation. Often, the “standard formulation” used to assess bioavailability is the aqueous solution of the drug, administered intravenously. The amount of drug absorbed is taken as a measure of the ability of the formulation to deliver the drug to the sites of action of the drug; obviously, depending on factors such as the disintegration and dissolution properties of the dosage form and the rate of biotransformation in relation to the rate of absorption, dosage forms.

which contain identical amounts of active drug may differ markedly in their ability to make the drug available and, therefore, in their ability to allow the drug to manifest its expected pharmacodynamic and therapeutic properties. F, disintegration time, dissolution time, generic drugs, reference standard, equivalence, first-pass effect, AUC The movement of chemical substances (drugs) to, through and out of biological organisms or their parts. When studying biotranslocation, one deals with the identification and description of such movement, the clarification of the mechanisms by which they are produced, and the investigation of the factors that control them. Ultimately, studying biotranslocation involves considering how chemicals cross cell membranes and other biological barriers.

A form of experiment in which, to a certain extent, participants are kept ignorant of the nature and doses of the materials administered as specific parts of the experiment. The purpose of the device is, obviously, to avoid a biased interpretation of the observed drug effects and to prevent a supposed knowledge of the expected effects from influencing the types of effects experienced by a subject. Blind experiments are not limited to experiments involving only human subjects. Needless to say, both experimenters and subjects may have general knowledge of the purpose, materials and design of the experiment; their ignorance is limited to the nature of individual drug administrations.

In an “individual blind” experiment, a participant, usually the subject, is left uninformed. In a “double blind” experiment, two participants (usually the subject and the observer) are not informed, and in a “triple blind” experiment, the subject, the observer and the person responsible for the actual administration of the drug do not know the nature of the material administered. In clinical experimentation, in particular, the use of blind experimentation is often associated with the use of fictitious drugs or placebo as part of the experimental design, and with the use of a “crossover” experimental design. The fictitious concentration of a drug or chemical substance in the plasma at the time (in theory) of an instantaneous intravenous injection of a drug that is distributed instantaneously to its volume of distribution.

C0 is determined by extrapolating, at zero time, the graph of log C against t (for apparently “first-order decrease of C”) or of C against t (for apparently “zero-order decrease of C”). Css, f, multiple dose regimens Cf. Multiple-dose regimens, infusion kinetics, first-order kinetics Pharmacological treatment of parasitic or neoplastic diseases in which the drug has a selective effect on invading cells or organisms. Some indices of relative safety or relative efficacy cannot be explicitly and uniquely defined, although it is assumed that the same quantifiable and accurate criteria of efficacy and safety will be used when comparing drugs of similar types.

The Food and Drug Administration has considered that the following definition of an improved clinical therapeutic index is used to compare different combinations or formulations of drugs; the assumption that an improved or better drug has a higher clinical therapeutic index (greater safety (or patient) remains acceptance) at an accepted level of efficacy within the recommended dosage range, or (increased efficacy at equivalent levels of safety (or patient acceptance) within the recommended dosage range. Cf. Food and Drug Administration, therapeutic index, standardized safety margin, effective The space or spaces in the body that a drug appears to occupy after it has been absorbed. Pharmacokinetic compartments are mathematical constructs and need not correspond to the volumes of fluid in the body that are physiologically and anatomically defined, that is,.

Some medications cause the body to “behave as if it consisted of a single pharmacokinetic compartment.”. The tissue and plasma concentrations of the drug rapidly and simultaneously reach equilibrium in all tissues to which the drug is distributed. A graph of plasma concentration as a function of time after intravenous administration can be rectified in a single straight line with a negative slope, which can intersect with the one ordered at a single point; only one volume of distribution can be calculated. Therefore, the existence of a single compartment or distribution volume can be inferred.

The compartments in which equilibrium is reached relatively late are called “deep compartments”; the compartments in which equilibrium is achieved early, and from which the drug is redistributed to other sites, are called “shallow” or “superficial” compartments. The extent to which the patient accepts and follows a prescribed treatment regimen. A form of experiment in which each subject is prepped for the exam at least once, and each test preparation is administered to each subject. In successive experimental sessions, each preparation “crosses” from one topic to another.

The purpose of the crossover experiment is to allow studying the effects of each preparation on each subject and to allow the data of each preparation to be similarly and equally affected by the peculiarities of each subject. In a well-designed crossover experiment, if possible, the sequence in which the test preparations are administered is not the same for all subjects, in order to avoid biases in the experiment as a result of changes in the behavior of the subjects that are a function of time rather than of drug administration or a function of drug interactions. At least, the cross-over design makes it possible to detect such biases when they occur. Preparations being tested in a crossover experiment may, ideally, include one or more doses of an experimental or “unknown” drug, one or more doses of a dummy drug or placebo (“negative control drugs”) and one or more doses of a standard drug, whose actions are expected to be similar to those of the “unknown” (” positive control drug”).

Even for the researcher with the best knowledge and intentions, the economics and logistics of experimentation can make it impossible to carry out a complete and perfect cross-over experiment. Bioassay, positive control drug, blind experiment Tolerance to a drug that is generalized to drugs that are chemically related or that produce similar effects. For example, a patient who is tolerant to heroin will also have a cross-tolerance to morphine. A measure of the “potency” of the drug calculated from data appropriate for the construction of a time-concentration curve; the product of the concentration (C) of an agent applied to a biological system to produce a specific effect and the duration (T) of the application required to produce the effect.

The index is calculated assuming that the time-concentration curve is hyperbolic and convex with precision and symmetry with respect to the origin, and that the products of the coordinates of all points on the line are constant. The time-concentration curve of an agent with a high potential to produce a specific effect is closer to the axis than the curve of an agent with a lower potential; the CT index of the agent with the highest potential is smaller than the index of the agent with the lowest potential, that is,. CT indices have found their greatest application in toxicology, in the evaluation of the potential effect of harmful vapors, etc. Dose (q, v).

Withdrawal symptoms, when they occur, can be relieved by administering the drug on which the body was “dependent”. Decreased response to repeated or sustained application of an agonist resulting from changes in the receptor level. Dissolution time, generic drugs, biopharmaceuticals The time required for a given amount (or fraction) of the drug to be released into solution from a solid dosage form. Dissolution time is measured in vitro, under conditions that simulate those produced in vivo, in experiments in which the amount of drug in solution is determined as a function of time.

It goes without saying that the availability of a drug in solution, rather than as part of an insoluble particulate material, is a necessary prerequisite for drug absorption. Disintegration time, bioavailability, generic drugs, biopharmaceuticals Cf. Dosage form, multiple dose regimens A characteristic, even the sine qua non condition, of a true pharmacological effect is that a higher dose produces a greater effect than a smaller dose, up to the limit to which affected cells can respond. Although it is characteristic of a pharmacological effect, this relationship is not exclusive to active drugs, since the increase in doses of placebos (q, v).

Distinguishing between “true” and “inactive” drugs requires more than demonstrating the relationship between “dose” and “effect”. A chemical substance used in the diagnosis, treatment, or prevention of a disease. More generally, a chemical substance that, in a solution of sufficient concentration, will modify the behavior of cells exposed to the solution. Drugs produce only quantitative changes in the behavior of cells; that is,.

The drugs used in therapy never produce qualitative changes in cellular behavior without causing cell death, e.g. ex. It remains to be seen to what extent this point of view will be modified by the discovery and development of agents that act on cells at the genetic level. Drug addiction, addiction, habituation, Harrison Law Cf.

Addiction, Hiring, Drug Abuse, Harrison Act Cf. Placebo, negative control drug, Cf crossover experiment. As originally formulated by Stephenson (195), is the binding of an A agonist to its R receptor considered to produce an “S%3D stimulus”? A x P AR where? A is the effectiveness of A and PAR is the proportion of busy receivers. The effect of the drug on the cell or tissue is given by the %3D effect f (S), where f is an unspecified monotonic function that depends on the nature of the receptor and its interaction with the cell or tissue.

Efficacy is both agonistic and tissue-dependent. Equally potent or equally capable of producing a pharmacological effect of a specific intensity. The masses of drugs needed to produce this degree of effect can be compared, quantitatively, to obtain estimates of the potency of the drugs. Obviously, if two drugs are not capable of producing an effect of a certain intensity, they cannot be compared with respect to potency; that is,.

Half-Life, Cmax, Css, multi-dose regimens, infusion kinetics, compartment (s), first-order kinetics An agency of the Department of Health and Human Services that is responsible for ensuring compliance with the amended Federal Food, Drug and Cosmetic Act. This agency must make a judgment on the safety of drugs, the labels placed on drug packages and all the printed material that accompanies a packaged drug before that drug can be introduced into interstate commerce. Transmit the effectiveness of a new drug or pharmaceutical preparation and grant the agency maximum jurisdiction over clinical trials of a drug before its general sale and use is approved. Prosecution for violation of standards F, D.

The Act is enforced by the Office of the Attorney General on the recommendation of F, D, A. Drug formulations of identical composition with respect to the active ingredient, i.e. Drug dosage forms considered “generically equivalent” are more properly considered “chemically equivalent”, since they contain a designated amount of chemical drug in a specific stable state and meet the requirements of the pharmacopoeia in terms of chemical and physical properties. It is well known that a number of factors other than the amount of drug present in a dose can determine the ultimate therapeutic utility of the drug preparation, and even the availability of the drug at the site of action once the preparation has been administered.

Drugs can be generically equivalent, but not therapeutically equivalent. Factors affecting the therapeutic utility or efficacy of pharmaceutical preparations include the appearance, taste, disintegration and dissolution properties of the preparation, the interaction of active materials with other ingredients, including binders and solvents, pH, particle size, age of preparation, manufacturing conditions, such as the degree of compression of tablets and the nature and amount of coating of enteric-coated tablets. When the patent for a patented drug expires, the manufacturer must establish the biological equivalence of its generic formulation to market the product. To do this, the bioavailability of the generic formulation is compared with the patented product in a crossover experiment.

A condition characterized by a psychological desire for the effects produced by the administration of a medication. Addiction, Narcotics, Dependence, Tolerance, Drug Dependence The half-life of a drug in plasma or serum is often considered as an indication of the drug's persistence in its volume of distribution; this interpretation may be incorrect unless the material can move freely and quickly from a liquid compartment from body to body, and is not tied or stored in one or the other tissue. The term “biological half-life” should not be used instead of the specific terms “plasma half-life” or “serum half-life”. You should always specify the tissue for which the half-life of a drug is determined, e.g.

The half-life of drugs is often based on the results of chemical analysis, that is,. When the logarithm graph of plasma or serum concentration (during the period of its decline) with respect to time is composed of two segments in a straight line, it can be inferred that two first-order processes are involved in drug distribution, biotransformation and elimination. The anterior phase, represented by the linear segment with the greatest slope, is called the distributive phase and corresponds to the period during which the drug is translocated to its final volume of distribution and is the dominant process; the subsequent phase, represented by the line with the lowest slope. — it is called the elimination phase and corresponds to the period in which biotransformation and drug elimination are dominant processes.

For two-phase systems, three-phase systems, etc. In the case of chemicals, such as drugs, it is often more informative to consider their hazards in relation to their potential to produce benefits, than in relation to the dangers of other chemicals. An extremely potent therapeutic agent can also be potent in causing harm, but it can be a useful drug because of its high therapeutic index or its standardized safety margin. Risk, potency, therapeutic index, standardized safety margin, TC index, toxic effects The physiological state necessary for a subject to manifest an allergic response or reaction; the condition depends on the administration of a hapten or allergen to a susceptible individual and on the development of antibodies and mechanisms Immune agents capable of being activated by subsequent administration of the hapten.

Hypersensitivity may exist, but not manifest until a second administration of hapten occurs. The dose of hapten (or drug) needed to produce the allergic response may be smaller, greater or the same size than the dose required for the drug to produce its characteristic pharmacological effects; therefore, hypersensitivity is not the same as sensitivity and the two words should not be used synonymously. The nature of the hapten response in a hypersensitive subject is determined by immune mechanisms and effector organs and, in general, is not related to the nature of the hapten; the allergic response in the hypersensitive subject is generally qualitatively different from the expected pharmacodynamics. response to the hapten or drug, determined by the immune system and not by the receptors that mediate the pharmacodynamic effect of that drug.

A drug that produces a state clinically identical to sleep by acting on the central nervous system. Toxic effects, side effects, allergic response Infusion, as a means of drug administration, involves a continuous and effective flow of a drug solution into the bloodstream over a relatively long period of time. Intravascular injections are separate administrations of drug solutions, each for a short period of time. Css, F, multiple dose regimens, first-order kinetics, compartment (s) The property of a drug that determines the amount of biological effect produced per unit of drug-receptor complex formed.

Two agents that are combined with equivalent sets of receptors may not produce the same degrees of effect, even if both agents are administered at maximally effective doses; the agents differ in their intrinsic activities and the one that produces the greatest maximum effect has the greatest intrinsic activity. Intrinsic activity is not the same as “potency” and can be completely independent of it. Presumably, meperidine and morphine 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 highest intrinsic activity. Intrinsic activity, such as affinity, depends on the chemical nature of both the drug and the receptor, but intrinsic activity and affinity may apparently vary regardless of changes in the drug molecule.

Antagonism, dose-effect curve The period of time that must elapse between the time a drug dose is applied to a biological system and the time when a specific pharmacological effect occurs. In general, the latency period varies inversely with the dose; the relationship between dose and latency period for a given agent is described by a time-dose or time-concentration curve. A higher than normal dose (D*) given as the first in a series of doses, the rest of which are smaller than D* but equal to each other. The loading dose is administered in order to achieve a therapeutic amount in the body more quickly than would occur only by accumulating smaller repeated doses.

The smaller doses (D) given after D* are called a “maintenance dose”. The effect of D* on C is relatively reduced with each successive maintenance dose; finally, Css, max and Css, min are determined by D and are not influenced by D*. Dose, Cmax, Css, F, multiple dose regimens The predicted dose of a drug (using statistical techniques) will produce a characteristic effect in 50 percent of the subjects to whom the dose is administered. The average effective dose (usually abbreviated ED50) is obtained by interpolation based on a dose-effect curve.

The ED50 is the most commonly used standardized dose by which drug potencies are compared. Although the dose of the drug that is expected to be effective at one percent (DE) or 99 percent (ED9) of a population can be determined, the ED50 can be determined more precisely than other similar values. An ED50 can only be determined from data that involves a total or no (quantum) response; for quantum response data, the values of ED0 and ED100 cannot be determined. In analogy with the average effective dose, the pharmacologist speaks of an average lethal dose (LD50), a medium anesthetic dose (AD50), an average convulsive dose (CD50), etc.

Dose-effect curve, therapeutic index, standardized safety margin, bioassay, metometer A term used to designate “the measurement or transformation of the measurement used in the evaluation of biological tests”. Examples of dose metameters include “milligrams”, “moles”, logarithmic “milligrams”, “milligrams” per kilogram of body weight, etc. Response metameters include “increase in blood pressure”, in mmHg, “maximum blood pressure reached”, in mmHg, and “percentage increase in blood pressure”. Metameters are often and wrongly chosen only to facilitate statistical summary and data analysis; the metometer used can also obscure or influence the biological interpretation of the data in a way not foreseen or expected by the researcher.

For example, in calculating the “percentage change” in blood pressure, the statement that the final state of the system is a function of the initial state that may or may not be true is implicit. The pharmacokinetic aspects of treatment programs that involve more than one dose of a drug are discussed below. The relationships described involve assumptions of instantaneous intravenous administration and delivery of a drug that is removed by first-order kinetics from a single-compartment system and that is administered in equal doses at equal intervals of time. Relationships become less precise when describing real situations to the extent that real systems depart from the ideal model, that is,.

To the extent that ka is not much larger than kel, and to the extent that Vda is not much smaller than Vdb. Where time is required (isn't it?) is expressed as the product of the number of doses and the duration of the dose interval (?). The number of doses needed to achieve the desired ratio of Cmax to Css, max can be determined by dividing the right element of the equation by the length of the dose interval. Cmax, Css, multiple dose regimens Cf.

Addiction, Anesthetic and Analgesic Reference volume previously published by the American Pharmaceutical Association containing purity standards and test methods for some drugs, as well as formulas and manufacturing methods for a variety of pharmaceutical preparations. Drugs were included based on demand and therapeutic value. As official standards, and both are now published in a single volume. US, P, P.

Positive control drug, fictitious, placebo, bioassay, cross-experiment 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 chemical substances (drugs) and organisms. Pharmacogenetics involves the identification and description of these patterns, their discrimination from non-hereditary patterns, and the elucidation of the mechanism of inheritance.

Pharmacogenetic studies reveal many intraspecific and interspecific similarities and differences in pharmacodynamic and pharmacokinetic mechanisms. Pharmacodynamics, pharmacology The science and study of factors that 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. Pharmacokinetics includes the study of the absorption and distribution of drugs (“biotranslocation”), the study of the chemical alterations that a drug may undergo in the body (“biotransformation”) and the study of the means by which drugs are stored in the body and removed from it. Pharmacodynamics, Pharmacology, Biotransformation, Biotranslocation, Half-life, Volume of distribution, Bioavailability Gr.

Pharmakon (medicine) and Logos (word) is the study of medicines in all their aspects. Pharmacy, although often confused with pharmacology, is, in fact, an independent discipline that deals with the art and science of drug preparation, composition and dispensing. Pharmacognosy is a branch of pharmacy that deals with the identification and analysis of plant and animal tissues from which drugs can be extracted. Pharmacodynamics, commonly referred to as “pharmacology”, is concerned with the study of the effects of drugs and how they are produced.

The pharmacodynamist 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 the actions of drugs occur. The pharmacologist also investigates factors that modify the effects of medications, that is,. The routes of administration, the influence of absorption rates, the differential distribution, and the mechanisms of excretion and detoxification of the body on the overall effect of a drug.

Pharmacotherapeutics is the study of the use of drugs in the diagnosis, prevention and treatment of disease states. Toxicology is the study of the effects of drugs that are harmful to health. The toxicologist can investigate problems as diverse 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 death that would otherwise be unexplained, etc. Therapeutics, Pharmacodynamics, Pharmacokinetics, Pharmacogenetics, Toxicology Cf.

Dummy negative control drug, positive control drug Cf. Negative control drug, bioassay, crossover experiment, reference standard Expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect; an imprecise term that must always be defined in more detail (see EC50, ED50). A chemical substance with little or no pharmacological activity that is transformed in the body and becomes a more active material. The change may be the result of biotransformation, or it may occur spontaneously, in the presence of, p.

Specifically, accuracy is calculated in several steps. First, the deviation of each observed output value from the corresponding predicted value is squared; the predicted values are determined from the curve that relates the input and output of all data. The squared deviations are added and divided by N-2, the number of “degrees of freedom”; the square root of the quotient is determined and is a number analogous to the standard deviation. This “mean square deviation” is then divided by the slope of the entry-exit curve, that is,.

Intrinsic activity, affinity, antagonism A drug, chemical substance or dosage form, etc. The purpose of such a comparison is to express the quantity or degree of the designated property in the “other” material as a fraction or multiple of the quantity or grade of the property contained in the standard. The reference standard serves as a unit of measurement for the properties of the other material, or “unknown” material. Even physical measurement systems are based on reference standards.

The use of reference standards is particularly important for the design and interpretation of biological experiments. In biological experiments, in particular, the variability and instability of the biological test system can significantly influence the apparent effects and efficacy of the substances being tested. The extent to which the input-output ratio is reproducible if the relationship is studied repeatedly under comparable conditions. For example, if a student took the same test twice or in two ways, would they get the same grade both times? If the same work were reviewed by two evaluators, would they both assign the same grade? The likelihood that the damage will result from exposure to a hazard.

More generally, the probability that an event occurred, or will occur, in members of a population under specific conditions, for example,. The risk is calculated by dividing the number of subjects experiencing an event by the number of subjects in the at-risk population. The risk, thus calculated, is one of the bases used to estimate the probability that the event will occur in the future, the expected risk. The risk, calculated as described, also indicates the probability that any individual subject in the at-risk population experienced the event.

Formally, the idea of “risk” is applicable to the study of both desirable and undesirable events. To interpret a risk estimate, it is necessary to compare the data with those of a “control population”, ideally one that is never exposed to danger. The statistical techniques used to estimate risks and compare them are, in general, the techniques used in epidemiology. Perceived risk is the subjective assessment of the importance of a hazard to individuals or groups of people.

For example, hazards affecting children generally have higher perceived risks than those that tend to affect adults. Hazards that are considered to be under a person's control (p. Dangers that cause deaths clustered in time and space (for example, g. Perceived risks are not necessarily correlated with risks, for the same hazards, measured by epidemiological techniques.

Risk management is the effort to reduce the likelihood that a hazard will cause harm. Risk management may involve reducing the size of the population at risk (p. Selectivity is generally a desirable property in a drug, e.g. Sometimes, the selectivity of the action is practically excluded by the nature of the drug, e.g.

Sometimes, the selectivity of the action of the cells of an organism is not necessarily desirable, as in the case of certain economic poisons, that is,. The ability of a population, individual, or tissue, relative to the abilities of others, to respond qualitatively normally to a particular drug dose. The lower the dose required to produce an effect, the more sensitive the response system is. A patient would be considered to be abnormally sensitive to aspirin if a small fraction of the normal dose of pain reliever provided adequate pain relief; or if an abnormally high dose of aspirin were needed to relieve pain, the subject would be said to be “insensitive” to aspirin.

On the contrary, the drug would appear to be extraordinarily potent or impotent in such a patient. If a patient manifested an allergic response after ingesting aspirin, they would be considered hypersensitive to aspirin, regardless of whether aspirin provided pain relief and the size of the dose required to cause the allergic response. Such a patient may be simultaneously hypersensitive to aspirin and insensitive to aspirin, acting as an analgesic agent. Every subject is sensitive to a drug; the important question is “how sensitive are they? In any case, sensitivity is a property attributed to the body; potency is a property attributed to the drug.

Hypersensitivity is a property attributed to a subject in a particular immune state. Sensitivity can be measured or described quantitatively in terms of the point of intersection of a dose-effect curve with the absciscisal value axis or a line parallel to it; this point corresponds to the dose that is only needed to produce a given degree of effect (see Threshold). In analogy with this, the “sensitivity” of a measurement system is defined as the lowest input (the smallest dose) required to produce a given degree of output (effect). Supersensitivity, hypersensitivity, allergic response, potency, accuracy Pharmacological effects that are not desirable or are not part of a therapeutic effect; effects other than those expected.

For example, in the treatment of peptic ulcer with atropine, dry mouth is a side effect and decreased gastric secretion is the desired pharmacological effect. If the same drug were used to inhibit salivation, the therapeutic effect would be dry mouth and a decrease in gastric secretion would be a side effect. A drug system has excess receptors (a reservoir of receptors), if an agonist can induce a maximum response when it occupies less than 100% of the available receptors. The existence of reserve receptors reflects a circumstance in which the maximum effect produced by an agonist is limited by a factor other than the number of activated receptors.

Whether or not a system has excess receptors depends on the nature of the receptor and its coupling to the measured response, the number of receptors and the intrinsic activity of the agonist. The ability of a drug to manifest only one type of action. A drug with perfect specificity of action could increase or decrease a specific function of a certain type of cell, but it wouldn't do both. Nicotine is not specific in its actions on the autonomic ganglia; it stimulates and depresses lymph node function by several means.

Atropine is highly specific because it only blocks the action of acetylcholine on certain receptors; in general, atropine does not stimulate cellular activity when combined with receptors, nor does it block the interaction with the receptors of agonists other than acetylcholine. By affecting the exocrine glands, acetylcholine itself is very specific, since it only causes stimulation or secretion; acetylcholine, at the same time, is not selective in its action, since the stimulation of all exocrine glands occurs with approximately the same dose of acetylcholine. 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, to a certain extent, is inherent to every organism; supersensitivity is a state that has had to occur in the body. In the supersensitive subject, the actions of the drug are qualitatively similar to those observed in a subject of normal sensitivity, and unlike those produced in a subject who is hypersensitive to the drug. A drug interaction that reinforces each other, so that the combined effect of two drugs administered simultaneously is greater than the sum of their individual effects. Synergy is distinguished from additivity, in which the combined effect of two drugs is equal to the sum of their individual effects.

If the combined effect is less than the sum of the independent effects of the two drugs, the interaction is said to be antagonistic. A point in time or an interval of time; often, an interval of time after administration of a drug or the interval of time between doses of a drug. The definition of a T or H. specific can be explicit or can be inferred from the context in which it is found.

Specific interest times can be indicated by subscripts, for example,. Decreased response to repeated applications of agonists, which typically occurs on a relatively short time scale (from seconds to hours). The therapeutic index is a measure of drug selectivity, and similar index numbers are often calculated 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, ED50 for causing ataxia in mice could be compared to ED50 for eliminating electrically induced seizures in mice.

Average effective dose, selectivity, standardized safety margin, clinical therapeutic index Drugs can be used prophylactically to prevent disease or to reduce the severity of a disease if it occurs after or during treatment; with great disregard for the accuracy of the definition, such use of Medication is commonly called “prophylactic therapy”. Medications are sometimes used to measure body function and contribute to the diagnosis of the disease; these diagnostic agents have not yet been accused of participating in “diagnostic therapy”. A dose of drug sufficient to produce a preselected effect. Often, and inappropriately, the dose is restricted enough to produce a minimal detectable effect.

In fact, an LD50 is a threshold dose if the preselected effect is “death” in 50% of the population. 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 achieve the same effect, or the original level of effect may be unattainable. Tolerance generally develops over days or weeks, and is distinguished from tachyphylaxis, a more rapid decrease in the effect of a medication.

Tolerance can result from multiple mechanisms, including changes in drug metabolism and alteration in the number or responsiveness of receptors (see desensitization). An unusual drinker who isn't affected by several shots of whiskey consumed in quick succession is likely to be insensitive to alcohol rather than tolerant to its effects. The scientific discipline concerned with understanding the mechanisms by which chemical substances produce harmful effects on living tissues or organisms; the study of the conditions (including dose) in which the exposure of living systems to chemicals is dangerous. Hazard, Pharmacology, and Toxic Effects A Simplified Model of Receptor Activation by Agonists.

It is hypothesized that the receptor is in a conformational balance between an inactive R conformation and an active R* conformation, with the equilibrium in the absence of an agonist normally favoring the inactive state. With greater affinity () with the active state, and through mass action, they change the conformational balance in such a way that a greater proportion of receptors are in the active R* conformation. Inverse agonists shift the conformational balance in such a way that a greater proportion of receptors are in the inactive R* conformation. The United States Pharmacopoeia is a reference volume published every five years by the U.S.

Department of State. Pharmacopoeian Convention, which describes and defines approved therapeutic agents, as well as establishes standards for purity, testing, etc. Agents are included based on their therapeutic value. As an official standard for the agents described therein.

The degree to which the production reflects what it is intended to reflect, that is,. For example, does an essay test validly measure a student's knowledge of the material, or is it not valid to actually measure their literary ability or the student's state of digestion? The volume, in an organism, throughout which a drug appears to have been distributed; the volume in which a drug appears to have dissolved after administration to an organism. Assuming that the concentration of the drug in the plasma (or serum) reflects the average concentration of the drug throughout its volume of distribution, the plasma concentration can be graphically represented as a function of the time after administration of the drug, and the resulting line can be extrapolated to obtain a concentration fictitious (C0) “was predicted to exist at the time the drug was administered, also assuming the instantaneous and complete administration, absorption and distribution of the drug. Obviously, C0 is the value that is expected to have occurred at a time when the biotransformation and excretion mechanisms did not have a significant effect on the amount of drug in the body.

Needless to say, for a correct interpretation of C0, it is assumed that the drug measured in plasma is identical to the agent that was administered and that the drug did not undergo any chemical alteration during its administration, absorption or distribution. Two more requirements: first, special care must be taken mathematically to obtain volumes of distribution that can be validly interpreted when the binding of the drug to the plasma protein significantly restricts the mobility of drug molecules. Secondly, when the graph of plasma concentration as a function of time shows a system that includes two (or more) phases, that is,. Chemical reaction mechanisms in which the reaction rate is apparently independent of the concentration of all reagents.

Typically, in biological systems, one reagent (X) is present at a much higher concentration than the other (Y), but is capable of undergoing changes, while the concentration of Y, on the contrary, does not undergo substantial changes during the course of the reaction. For example, consider the inactivation of a drug (X), present in the body in an overwhelming amount, by an enzyme (Y) present in a limited concentration in cells and that has a specific maximum capacity to inactivate X. A sufficiently high concentration of X would “saturate Y” and cause the system to effectively operate at its maximum speed; the amount of inactivated X per unit of time would be constant and would depend on the maximum velocity per mass of Y and the total amount of Y present in the body; modest changes in a concentration of X would not change In a detectable way the speed of the system that is operating practically at its maximum speed. Remember the shape of the velocity and substrate concentration curve.

Finally, the concentration of X would decrease to the point where it did not saturate Y, and the inactivation would proceed according to first-order kinetics. Most drugs undergo chemical alterations by various body systems to create compounds that are more easily excreted from the body. These chemical alterations occur mainly in the liver and are known as biotransformations. Knowing these alterations in chemical activity is crucial to using the optimal pharmacological intervention for any patient and, therefore, is of interest to any provider who routinely treats patients with medications.

This activity covers drug metabolism, biotransformations and polypharmacy, and highlights the role of the interprofessional team in caring for patients receiving multiple medications. Drug metabolism is a crucial aspect of medical practice and pharmacology. Understanding these alterations in chemical activity is crucial to using the optimal pharmacological intervention for any patient and is therefore of interest to any provider who routinely treats patients with medications. For example, if 5 milligrams of drug A relieves pain as effectively as 10 milligrams of drug B, drug A is twice as potent as drug B.

Since these idealized conditions are practically unattainable, the volume of distribution of a drug can only be approximated using experimental data. . .

Wade Pflughoeft
Wade Pflughoeft

General beer guru. Freelance web junkie. Unapologetic tv geek. Award-winning beer lover. Subtly charming internet buff.

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