A Collection of Therapeutic, Toxic and Fatal Blood Drug Concentrations in Man

Abstract

<jats:p> 1 In order to assess the significance of drug concentrations measured in clinical and toxicological investigations, it is essential that good collections of data are readily available. As a guide to interpreting findings, the present work provides a compilation of therapeutic, toxic and fatal blood concentration ranges of 298 drugs of interest to clinical pharmacologists, clinical toxicologists, and forensic toxicologists. </jats:p><jats:p> 2 Wherever possible, ranges are expressed concisely in terms of the maximum blood concentrations which account for 10, 50 and 90% of the data collected. They provide easy access to the most reliable information which relates the blood drug concentration to the biological response it produces. Where appropriate, the different toxic effects of a drug and/or the different degrees of severity of toxic symptoms associated with different drug levels are clearly defined. </jats:p><jats:p> 3 The original sources of all data used are provided to allow the analyst to obtain further analytical, pharmacokinetic and toxicological information should this be necessary. </jats:p><jats:p> 4 Those factors (e.g. age, capacity for drug metabolism, drug interactions, etc) which can modify the relationship between a drug concentration and the response it produces are briefly discussed. </jats:p>

The mode of action of several opioids on cardiac muscle

“…A similar study with cat myocardium (Amsterdam, Rendig, Henderson & Madson, 1981) showed that dextropropoxyphene and norpropoxyphene reduced isometric twitch tension with near half-maximal effects at 100 ,um; by contrast, 100 /SM morphine had only a minimal negative inotropic effect, when maximal opioid receptor interaction would occur. The clinical relevance of these effects of opioid agents is indicated by the fact that the effective concentrations are similar to plasma levels found in human poisoning (Stead & Moffat, 1983), the mean fatal blood values being 44, 4.5, 32 and 57 /LM for dextropropoxyphene, methadone, pentazocine and pethidine, respectively. Thus, this negative inotropic effect may underlie the reduction of contractility and myocardial failure with in vivo toxicity of these opioids.…”

“…Thus these opioids could reduce the Na+ channel activity of cardiac cells and the data suggest that dextropropoxyphene, norpropoxyphene, methadone and pentazocine have an effect at least as strong as quinidine; pethidine was less potent. Again, the effective concentrations are of the order of those found in human poisoning (Stead & Moffat, 1983). …”

Therapeutic Potential of Monoamine Transporter Substrates

“…Given that plasma DA levels are about 10-fold less than plasma NE levels, and DA is a precursor in NE biosynthesis, we believe that these stimulants release both NE and DA from peripheral noradrenergic nerves. The plasma levels of the various drugs tested in baboons were at the high end of typical therapeutic plasma levels observed in human subjects (1-3 µM) [57,58]. These data suggest, therefore, that typical clinical doses of phentermine and (±)-ephedrine may not release central DA in humans.…”

Simplified Analysis of Toxic Gaseous Substance in Forensic Practice: Experiences from Japan

“…Since the physiological effects of most gaseous substances correlate with the concentration in blood, it becomes the best indicator of toxicity [4]. As numerous reference tables for fatal levels of chemicals have been reported [5][6][7][8][9], forensic diagnosis is made in reference to the values reported in the data tables. In addition, several other factors have to be considered for toxicological evaluation; these include the properties of the sample, diffusion and redistribution, degradation, and metabolism [1,2,10,11].…”