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. The smaller the dose required to produce an effect, the more sensitive is the responding system. A patient would be considered abnormally sensitive to aspirin if a small fraction of the normal analgesic dose gave adequate pain relief; or, were an abnormally large dose of aspirin required to afford pain relief, the subject would be said to be “insensitive” to aspirin. 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.

Every subject is sensitive to a drug; the question of importance is “how sensitive?” In any event sensitivity is a property ascribed to the organism; potency is a property ascribed to the drug. Hypersensitivity is a property ascribed to a subject in a particular immunologic state.

Sensitivity may be measured or described quantitatively in terms of the point of intersection of a dose-effect curve with the axis of abscissal values or a line parallel to it; such a point corresponds to the dose just required to produce a given degree of effect (see Threshold”). In analogy to this, the “sensitivity” of a measuring system is defined as the lowest input (smallest dose) required to produce a given degree of output (effect).

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Prodrug definition:

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.g., water, an appropriate pH, etc.

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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. 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.

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Loading Dose:

A larger than normal dose (D*) administered as the first in a series of doses, the others 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 rapidly than would occur only by accumulation of the repeated smaller doses. The smaller doses (D) which are given after D* are called “maintenance doses”. The effect of D* on C becomes relatively less with each succeeding maintenance dose; finally Css,max and Css,min are determined by D, and are uninfluenced by D*.

The relative sizes of D and D* can be adjusted so that peak plasma concentrations (Cmax) are the same following every dose, including the first with D*, and all are equal to Css,max. These conditions are met when D/D* = 1-f.

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Idiosyncratic Response:

A qualitatively abnormal or unusual response to a drug which is unique, or virtually so, to the individual who manifests the response. “Idiosyncratic Response ” usually applies to a response that is not allergic in nature and cannot be produced with regularity in a substantial number of subjects in the population, and which is ordinarily not produced in a greater intensity in an individual, or in a greater fraction of the population, by the expedient of increase in the dose. 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.

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ka:

The “absorption rate constant” for a drug administered by a route other than the intravenous. The rate of absorption of a drug absorbed from its site of application according to first-order kinetics. ka is determined directly, or indirectly, as the slope of the linear relationship between the logarithm of the amount un absorbed and t, when natural logarithms, i.e. logarithms to the base e, are used. The half-time for absorption is computed as 0.693/ka, i.e. ln 2/ka.

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Recommended pharmacokinetics reading

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. (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.e. to achieve and maintain Css.

The Css achieved during infusion of a drug is directly proportional to the rate of drug administration (D/T, or k0), and inversely proportional to both the rate of elimination (kel), and to the volume of body throughout which the drug is distributed: Css = (D/T)/kelVd. Since, kelVd equals total clearance: Css = (D/T)/ClT, or Css = k0/ClT. 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 Css is achieved depends only on the half life of the drug. In the absence of other doses (such as a loading dose [q.v.]) the plasma concentration at any time after beginning the infusion (CT), expressed as a fraction of the Css to be achieved, is given by (1 – f):

CT/Css = 1 – 0.5T/t½

After duration of infusion of one half-life, 50% of the final concentration will have been achieved; after a duration of infusion of 4 half-lives, about 95% of the final concentration will have been achieved.

The copyright of the quoted is hold by Trustees of Boston University. Permission has been granted for its use in this blog.

Recommended pharmacokinetics reading

kel:

The “elimination rate constant” for a drug eliminated according to the laws of first-order reaction kinetics; the slope of the plot of the logarithm of concentration against time, when natural logarithms, i.e. logarithms to the base e, are used.
t1/2 = 0.693/kel. kel = 2.303b. ClT = kel Vd. AUC from Tn to infinity = Cn/Kel.

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MORPHINES :

Miosis

Orthostatic hypotension

Respiratory depression

Pain supression

Histamine release/ Hormonal alterations

Increased ICT

Nausea

Euphoria

Sedation

Thanks to MedExcel

Equivalence:

In 1969, a federal Task Force on Prescription Drugs recommended that the words “generic equivalents” no longer be used in describing and comparing drug preparations. 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, or Bioequivalence:
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.

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