Semin Cutan Med Surg. Pramatarov KD. Drug-induced lupus erythematosus. Clin Dermatol. Ditto AM. Drug allergy. Patterson's Allergic diseases. Jick H. Adverse drug reactions: the magnitude of the problem.
J Allergy Clin Immunol. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. Einarson TR. Drug-related hospital admissions. Ann Pharmacother. General and epidemiological aspects of allergic drug reactions. Drug hypersensitivity reactions and human immunodeficiency virus disease.
J Acquir Immune Defic Syndr. Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol. Increased risk for anaphylactoid reaction from contrast media in patients on beta-adrenergic blockers or with asthma.
Ann Intern Med. Petri M, Allbritton J. Antibiotic allergy in systemic lupus erythematosus: a case-control study. J Rheumatol. Adkinson NF Jr. Risk factors for drug allergy. Cutaneous and systemic manifestations of drug-induced vasculitis. An approach to the patient with a history of local anesthetic hypersensitivity: experience with 90 patients.
Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. Patterson R. Drug allergy and protocols for management of drug allergies. Providence, R. Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.
Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults.
Arch Intern Med. In vivo and in vitro diagnosis of drug allergy. Immunol Allergy Clin North Am. Schwartz LB. Tryptase, a mediator of human mast cells. Shepherd GM. Allergy to betalactam antibiotics. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Drug-related lupus. Incidence, mechanisms and clinical implications. Drug Saf. Craven NM. Management of toxic epidermal necrolysis.
Hosp Med. Imipenem cross-reactivity with penicillin in humans. Lack of cross-reactivity between aztreonam, a monobactam antibiotic, and penicillin in penicillin-allergic subjects. J Infect Dis. Immunogenicity and cross-allergenicity of aztreonam. Am J Med. Lin RY. A perspective on penicillin allergy. Pumphrey RS, Davis S. Under-reporting of antibiotic anaphylaxis may put patients at risk. Cephalosporin allergy. N Engl J Med. Greenberger PA, Patterson R.
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Videos Figures Images Quizzes Symptoms. General references. Symptoms and Signs. Diagnosis reference. Prevention references. Test your knowledge. Most of the absorption of an oral drug occurs in which of the following structures? More Content. Click here for Patient Education. Idiosyncratic ADRs can produce almost any symptom or sign and usually cannot be predicted. Consideration of rechallenge. Modification of dosage.
Was This Page Helpful? Yes No. Introduction to Concepts in Pharmacotherapy. Drug Hypersensitivity. Drug Bioavailability. 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.
Since these idealized conditions are unobtainable in practice, the volume of distribution of a drug can only be approximated using experimental data. Obviously, C 0 , is the value expected to have occurred at a time when mechanisms of biotransformation and excretion had no significant effect on the amount of drug in the body.
Needless to say, it is assumed for proper interpretation of C 0 , that the drug as measured in the plasma is identical to the agent that was administered, and that the drug underwent no chemical alteration in the course of administration, absorption, or distribution. When C 0 is divided into the mass of the total dose administered, the quotient indicated the volume into which the drug appears to be dissolved. When C 0 is divided into dose expressed in terms of body weight e. The volumes, or fractions, can be readily compared with parts of body weight occupied by the various fluid compartments e.
A volume of distribution corresponding to more than about the volume of total body water is presumptive evidence that the drug is distributed nonuniformly throughout the body, and is concentrated at one or more sites, usually sites of drug storage, biotransformation or elimination, or at a site of drug application when a route of administration other than the intravenous one has been used.
Obviously, legitimate and valid interpretation of calculated volume of distribution depends on the degree to which experimental facts are in concordance with the assumption given above.
The idealized state is most closely approximated when the drug is given rapidly intravenously, and blood samples for chemical analysis of their drug content are taken at short intervals, beginning very soon after the time of drug administration.
Two more qualifications — first, special account must be taken mathematically, to yield validly interpretable volumes of distribution when binding of drug to plasma protein significantly restricts the mobility of drug molecules. Second, when the plot of plasma concentration against time gives evidence of a system involving two or more phases — i.
Compartment s , Pharmacokinetics , Half-Life , V d. Mechanisms of chemical reaction in which the reaction velocity is apparently independent of the concentration of all the reactants. Typically, in biological systems, one reactant X is present in a concentration greatly exceeding that of the other Y , but is capable of undergoing change, while the concentration of Y, in contrast, does not undergo substantial change during the course of the reaction.
For example, consider the inactivation of a drug X , present in the body in an overwhelming quantity, by an enzyme Y present in a limited concentration in cells and having a specific maximum capacity to inactivate X. Recollect the shape of the velocity — substrate concentration curve. The reaction velocity would be independent of the concentrations of both X and Y.
Eventually, the concentration of X would decrease to the point that it did not saturate Y, and the inactivation would proceed according to first-order kinetics. The amount of change in concentration per unit time is constant; in the case of first-order kinetics, the fractional change in concentration per unit time is constant. The elegant properties of multiple dose regimens q. Drugs that obey first-order kinetics with low doses may obey zero-order kinetics with large doses.
Error is defined as the algebraic difference between an indicated output value and the true measure of the input or measurand. Validity The degree to which output reflects what it purports to reflect, i. Reliability The degree to which the input-output relationship is reproducible if the relationship is studied repeatedly under comparable conditions.
Sensitivity The lowest value of input that can be inferred with a given degree of validity and reliability from measurements of output. Amplification The amount of change in measured output per unit change in input. Comparability The ability of a system to deliver data that can be compared in standard units of measurement and by standard statistical techniques with the data delivered by other systems. While not a critical component of accuracy, comparability of data generated by a system is critical to evaluating its accuracy and usefulness.
Activity, Intrinsic: See Intrinsic Activity. Affinity: The equilibrium constant of the reversible reaction of a drug with a receptor to form a drug-receptor complex; the reciprocal of the dissociation constant of a drug-receptor complex. Agonist: A ligand that binds to a receptor and alters the receptor state resulting in a biological response.
Agonist, Partial: A partial agonist is an agonist that produces a maximal response that is less than the maximal response produced by another agonist acting at the same receptors on the same tissue, as a result of lower intrinsic activity.
Agonist, Full: A full agonist is an agonist that produces the largest maximal response of any known agonist that acts on the same receptor.
Agonist, Inverse: An inverse agonist is a ligand that by binding to a receptor reduces the fraction of receptors in an active conformation, thereby reducing basal activity.
Allergic Response: Some drugs may act as haptens or allergens in susceptible individuals; re-administration of the hapten to such an individual results in an allergic response that may be sufficiently intense to call itself to the attention of the patient or the physician. Side-effects , Idiosyncratic Response , Hypersensitivity , Sensitivity Amplification: The amount of change in measured output per unit change in input.
Accuracy Analgesic: A drug that dulls the sense of pain. Antagonism: The joint effect of two or more drugs such that the combined effect is less than the sum of the effects produced by each agent separately.
Antagonisms may be any of three general types: Chemical caused by combination of agonist with antagonist, with resulting inactivation of the agonist, e. Physiological caused by agonist and antagonist acting at two independent sites and inducing independent, but opposite effects. Pharmacological caused by action of the agonist and antagonist at the same site. AUC: The area under the plot of plasma concentration of drug not logarithm of the concentration against time after drug administration.
Ordinarily, the relationship between changes in behavior of the indicator and differences in drug dose — a dose-effect curve — must be determined as a part of each assay. Potency is relative, not absolute. When the absolute amounts of standard used in the assay are known, the results of the assay can be used to estimate the amount — in absolute units — of biologically active material contained in the unknown preparation.
A bioassay provides only an estimate of the potency of the unknown; the precision of the estimate should always be determined, using the data of the assay. See: Bliss, C. Biotransformation , Biotranslocation , Pharmacokinetics , Bioavailability Biotransformation: Chemical alteration of an agent drug that occurs by virtue of the sojourn of the agent in a biological system.
Pharmacokinetics , Biopharmaceutics Biotranslocation: The movement of chemicals drugs into, through, and out of biological organisms or their parts. Pharmacokinetics , Half-Life , Volume of Distribution , Biopharmaceutics , k a , k el Blind Experiment: A form of experiment in which the participants are, to some degree, kept ignorant of the nature and doses of materials administered as specific parts of the experiment.
C 0 : The fictive concentration of a drug or chemical in the plasma at the time in theory of an instantaneous intravenous injection of a drug that is instantaneously distributed to its volume of distribution. Clearance , AUC , F Ceiling: The maximum biological effect that can be induced in a tissue by a given drug, regardless of how large a dose is administered. Intrinsic Activity Chemotherapy: Drug treatment of parasitic or neoplastic disease in which the drug has a selective effect on the invading cells or organisms.
Renal Clearance: Renal plasma or blood clearance Cl R is the volume of plasma or blood freed of a substance by only renal mechanisms, per unit time. Clinical Therapeutic Index: Some indices of relative safety or relative effectiveness cannot be defined explicitly and uniquely, although it is presumed that the same quantifiable and precise criteria of efficacy and safety will be used in comparing drugs of similar kinds.
Food and Drug Administration , Therapeutic Index , Standardized Safety Margin , Effective Compartment s : The space or spaces in the body, which a drug appears to occupy after it has been absorbed. Cross-Over Experiment: A form of experiment in which each subject receives the test preparation at least once, and every test preparation is administered to every subject. Bioassay , Positive Control Drug , Blind Experiment Cross-Tolerance: Tolerance to a drug that generalizes to drugs that are chemically related of that produce similar affects.
D: Dose q. Dependence: A somatic state which develops after chronic administration of certain drugs; this state is characterized by the necessity to continue administration of the drug in order to avoid the appearance of uncomfortable or dangerous withdrawal symptoms.
Addiction , Habituation Desensitization: A decline in the response to repeated or sustained application of an agonist that is a consequence of changes at the level of the receptor. Tachyphylaxis , Tolerance Disintegration Time: The time required for a tablet to break up into granules of specified size or smaller , under carefully specified test conditions. Dissolution Time , Generic Drugs , Biopharmaceutics Dissolution Time: The time required for a given amount or fraction of drug to be released into solution from a solid dosage form.
Dose: The quantity of drug, or dosage form, administered to a subject at a given time; for example, the usual dose of aspirin for relief of pain in an adult is milligrams. Dosage Form , Multiple Dose Regimens Dose-Duration Curve: The curve describing the relationship between dose as the independent variable and duration of drug effect as the dependent variable, T. Dose-Effect Curve , Time-Concentration Curve , Pharmacokinetics Dose-Effect Curve: A characteristic, even the sine qua non , of a true drug effect is that a larger dose produces a greater effect than does a smaller dose, up to the limit to which the cells affected can respond.
Some effect corresponds to every dose above the threshold dose q. The curve may have a positive slope, or a negative slope, but not both if the system under study is unique.
The slope of the curve may show varying degrees of positivity negativity , but the sign of the slope stays the same throughout the range of testable doses. When monotonicity of a dose-effect curve does not obtain, one may infer that the system under study is not unique or singular: either more than one active agent or more than one effect is under study.
The curves approach some maximum value as an asymptote, and the asymptote is a measure of the intrinsic activity q. In a quantal assay, the median effective dose. Food and Drug Administration , U. Elimination Rate Constant: See k el Equipotent: Equally potent, or equally capable of producing a pharmacologic effect of a specified intensity.
The Task Force recommended that an appropriate nomenclature should take into account three kinds of equivalence of drug preparations: Chemical Equivalents: Those multiple-source drug products which contain essentially identical amounts of the identical active ingredients, in identical dosage forms, and which meet existing physicochemical standards in the official compendia. Biological Equivalents: Those chemical equivalents which, when administered in the same amounts, will provide essentially the same biological or physiological availability, as measured by blood levels, etc.
Clinical Equivalents: Those chemical equivalents which, when administered in the same amounts, will provide essentially the same therapeutic effect as measured by the control of a symptom or a disease. Half-Life , C max , C ss , Multiple Dose Regimens , Infusion Kinetics , Compartment s , First-Order Kinetics F: 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.
Bioavailability , First Pass Effect , AUC First-Order Kinetics: 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. Addiction , Narcotic , Dependence , Tolerance , Drug Dependence Half-Life: 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. Narcotic , Addiction Hazard: The potential for causing harm; that which is a potential cause of harm.
Sensitivity , Allergic Response , Idiosyncratic Response Hypnotic: A drug that produces a state clinically identical to sleep by means of action in the central nervous system. Anesthetic I Return to top Idiosyncratic Response: A qualitatively abnormal or unusual response to a drug which is unique, or virtually so, to the individual who manifests the response. Toxic Effects , Side Effects , Allergic Response Infusion Kinetics: 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.
C ss , F , Multiple Dose Regimens , First-Order Kinetics , Compartment s Intrinsic Efficacy or Intrinsic Activity : The property of a drug that determines the amount of biological effect produced per unit of drug-receptor complex formed. L Return to top Latent Period or Latency: 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.
Parameter , Bioassay , Dose-Effect Curve Multiple Dose Regimens: The pharmacokinetic aspects of treatment schedules that involve more than one dose of a drug are discussed below. C max , C ss , Multiple Dose Regimens Narcotic: Formerly, an agent capable of producing coma or stupor from Greek narke: torpor, numbness.
Metameter , Bioassay Pharmacodynamics: 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. Pharmacology , Pharmacokinetics , Therapeutics , Pharmacogenetics Pharmacogenetics: The science and study of the inheritance of characteristic patterns of interaction between chemicals drugs and organisms.
Pharmacodynamics , Pharmacology Pharmacokinetics: 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.
Dummy , Negative Control Drug , Positive Control Drug Positive Control Drug: 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.
Negative Control Drug , Bioassay , Cross-Over Experiment , Reference Standard Potency: 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 Synergy , Antagonism Priming Dose: See Loading Dose Prodrug: A chemical with little or no pharmacologic activity that undergoes change in the body into a more active material.
Reliability: The degree to which the input-output relationship is reproducible if the relationship is studied repeatedly under comparable conditions. See Accuracy.
Risk: The likelihood that harm will result from exposure to a hazard. Hazard , Toxicology S Return to top Selectivity: The capacity or propensity of a drug to affect one cell population in preference to others, i.
Specificity , Therapeutic Index Sensitivity: 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.
Supersensitivity , Hypersensitivity , Allergic Response , Potency , Accuracy Side Effects: Drug effects which are not desirable or are not part of a therapeutic effect; effects other than those intended. Specificity: The capacity of a drug to manifest only one kind of action. Add or change institution. Save Preferences. Privacy Policy Terms of Use. Access your subscriptions. Free access to newly published articles. Purchase access. Rent article Rent this article from DeepDyve.
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