{"id":48148,"date":"2020-07-24T14:50:03","date_gmt":"2020-07-24T13:50:03","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=48148"},"modified":"2020-08-03T15:35:48","modified_gmt":"2020-08-03T14:35:48","slug":"jeffrey-aronson-when-i-use-a-word-power","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/07\/24\/jeffrey-aronson-when-i-use-a-word-power\/","title":{"rendered":"Jeffrey Aronson: When I Use a Word . . . Power"},"content":{"rendered":"

\"\"<\/a>Last week<\/span><\/a> I outlined some basic pharmacokinetic principles that can inform the likelihood that a newly proposed treatment may be effective, given only in vitro evidence. I showed that the highest tissue concentrations of ivermectin that are likely to be achieved after a single standard dose, the usual mode of administration, or even during repeated use of high doses to steady state, would fall a long way short of the in vitro concentrations that are needed to inhibit the SARS-CoV-2 virus, making ivermectin an unlikely candidate for effective treatment. Pharmacodynamic analysis can also be useful in predicting potential efficacy.<\/span><\/p>\n

\u201cPharmacodynamics\u201d, like \u201cpharmacokinetics\u201d, comes from two Greek words, in this case \u03d5\u03ac\u03c1\u03bc\u1fb0\u03ba\u03bf\u03bd and <\/span>\u03b4\u03cd\u03bd\u1fb0\u03bc\u03b9\u03c2, power or might (Figure 1). <\/span>The earliest uses of the noun \u201cpharmacodynamics\u201d and the adjective \u201cpharmacodynamic\u201d in English are from 1836 and 1846 respectively, over 100 years before the appearance of \u201cpharmacokinetics\u201d in the late 1950s. \u201cPharmakodynamik\u201d had already been used in German in 1823.<\/span><\/p>\n

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A pharmacodynamic effect involves an interaction between an extrinsic moiety, the drug, and an intrinsic moiety, which is usually a membrane-bound or intracellular receptor or an enzyme, or in the case of an infection some part of the infecting organism. Dexamethasone, for example, targets an intracellular host receptor; remdesivir targets the RNA-dependent RNA polymerase of the SARS-CoV-2 virus.<\/span><\/p>\n

The law of mass action <\/span>dictates<\/span><\/a> that there will be a relation between the concentration of the drug and the effect that it has on its target. This is illustrated in Figure 2.<\/span><\/p>\n

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Figure 2.<\/b> Concentration\u2013effect relationships for a series of alkylated trimethylammonium salts causing contraction in guinea-pig ileum in vitro<\/span><\/p>\n

The principle of the dose-response curve, stated in its simplest terms, is that:<\/span><\/p>\n