Themed issue Antidotes in Clinical Toxicology
Theophrastus Bombastus Paracelsus von Hohenheim (1493–1541) said it all with Dosis sola facit venenum or in modern language “It is the dose, stupid”. So, for a journal of Clinical Pharmacology that as a matter of principle deals with the relation between dose and effect, covering the high end of de dose – effect relationship is nothing out of the ordinary. This issue is largely about how to treat unfortunate patients who have reached the dark side of the dose–response curve. This can be done by antidotes.
Who gets antidotes? choosing the chosen few
Nicholas A. Buckley, Andrew H. Dawson, David N. Juurlink and Geoffrey K. Isbister
Our guest editor for this issue Nick Buckley writes about this issue that covers virtually all antidotes. Antidotes exist, but they are not as universally applicable and effective as in Harry Potter books. In the end they are just medicines with their own indications and potential side effects.
The thorough QT study – do we need more of the same?
Yoon K. Loke
When passing through any airport in the world one cannot escape the feeling being subjected to a lot of unnecessary research. It is very understandable, someone once upon a time tried to blow up a plane with his shoes so now the elderly couple in front of you also have to take their sensible shoes of, despite arthritic hands and knees. Somehow the a priori probability of them being loaded with explosives seems very low and the price paid in waiting time very high.
The same may be true for the thorough (meaning large) QT prolongation study. Once upon a time some drugs that prolonged QT produced some dangerous and sometimes deadly arrhythmias. Because of this, millions of normal ECG's have been collected (now often strangely enough in triplicate) from healthy volunteers on virtually every new drug. The pro‐arrhythmic effects can be predicted in vitro so the multitude of trials done at a cost of several billions are only to confirm the obvious.
Yoon Loke quite rightly questions if this is science and argues that publication should be done online rather than by taking up pages in scientific journals. One can also question if such research should be done at all, but stopping it is probably similarly impossible as keeping your shoes on during the security check.
In this issue the readers will get a full overview of virtually all available antidotes, their pharmacology and their therapeutic options.
Pharmacological treatment of acquired QT prolongation and torsades de pointes
Simon H. L. Thomas & Elijah R. Behr
When faced with drug induced seizures, or in the exceptional case when the drug induced QT prolongation has led to a torsades des pointes ventricular tachycardia this specialised issue will tell what to do and what not.
Adverse reactions to snake antivenom, and their prevention and treatment
H. Asita de Silva, Nicole M. Ryan & H. Janaka de Silva
Snakes are pharmaceutical factories of their own and administer a surprising range of pharmacologically active substances to affect physiological systems in such a way that they can devour their prey. Some of their prey, the humans, have devised antivenoms but the quality and evidence of these leave much to de desired.
Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new
Michael Eddleston & Fazle Rabbi Chowdhury
Although most people in the western world will never see organophosphorus intoxication due to safe agricultural practice and a good distance to the military use of these compounds, they will remember atropine and pralidoxime either from military service or from the autonomic pharmacology course. But in addition to a rich source of exam questions the clinical problem is real in many parts of the world and there is also additional evidence for other treatments. Magnesium sulphate, Clonidine and lipid emulsions all have been considered for OP poisoning. But do they work? Read this interesting paper!
Activated charcoal for acute overdose: a reappraisal
David N. Juurlink
Then there is always the ubiquitous antidote activated charcoal. Surprisingly cheap, with a reassuring black colour and presumably always effective and without side effects. O really? Like any medicine there is a black side to activated charcoal. Read all about it in the paper by David Juurlink.
In addition to the toxicology section of this issue there are also some interesting research papers on unrelated subjects.
Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach
Jens Markus Borghardt, Benjamin Weber, Alexander Staab, Christina Kunz, Stephan Formella & Charlotte Kloft
To estimate how much medicine is deposited in the lung is difficult and has to be derived indirectly from plasma concentrations after oral and pulmonary administration. Jens Marcus Borghardt uses a population based model for olodaterol. Interestingly about 50% of the drug reached the lung and appeared to have a much longer residence time there than expected from its physicochemical properties.