Toxicodynamics and toxicokinetics of exogenous poisons
‘All things are poisonous, but what makes them a poison is the dose’. We used to assess the toxicity of drugs and chemicals based on the LD50 value, this is the dose resulting in 50% of the animals in a sample, while we don’t use this precise method any longer, it illustrates a fundamental concept in toxicology that there is a dose-response relationship which applies to all toxins.
Toxicology is the branch of science that deals with poisons, which themselves are chemical/physical agents that produce adverse responses in the organism. The state of being ‘poisoned’ is a condition of organisms resulting from physical and chemical changes leading to disturbances of the organism under the influence of toxic substances.
Poisons can be defined as exogenous (from outside the body) or endogenous. While poisoning can be acute or chronic, have nonspecific symptoms, cause long term effects and even lead to the addiction.
Common causes of toxicity include therapeutic agents (i.e. drugs), industrial chemicals, household chemicals, environmental agents, natural toxins, and food additives.
Toxicodynamics deals with the biochemical and physiological effects of toxic substances to the body and mechanism of their action. Toxicokinetics deals with absorption, distribution, biotransformation and the excretion of toxic substances.
So, lets chat about toxicokinetics, if we remember our pharmacokinetics, its really the same, just for toxins! So, firstly, absorption. This depends on the route of administration, its ability to become ionized, its ability to be soluble, its concentration, blood flow to the site of administration, and the area of the absorptive site. Common sites of absorption are the oral (GIT route), dermal route and inhalational route.
Secondly, distribution, this is the apparent volume into which a substance is distributed. An important concept here is volume of distribution (Vd). This is calculated as dose/plasma concentration. This is important in toxicology in helping us to predict the peak blood concentration of the chemical taken, and allowing us to better understand the dose taken. Distribution depends on a number of factors, including: protein binding, plasma concentration, physiological barriers and the affinity of chemicals to certain tissues.
Thirdly, biotransformation (also known as metabolism) of the toxin, is part of toxicokinetics. Biotransformation can produce metabolites that are pharmacologically active and toxic (e.g. parathion to paraoxon). The liver is the most common site of biotransformation and consideration of the toxic metabolites of drugs is of vital importance. There are two important phases in toxicokinetics: