Download Pharmacology Corner: Dose-Response

Pharmacology Corner: Dose-Response
“Dosis facit venenum.” Or, in words we can all understand, “The dose makes the
poison.” This is a common adage first expressed by Paracelsus, the man known
as the Father of Toxicology (the study of the adverse effects of chemicals on
living organisms). The principle Paracelsus spoke about relies on the finding that
all chemicals—even water and oxygen—can be toxic if too much is eaten, drunk,
or absorbed. We have since learned a lot from his studies and now commonly
apply the pharmacodynamic term dose-response to poisons and medicines.
A substance can produce an effect associated with its therapeutic or toxic
properties (response) only if it reaches a susceptible biological system in a high
enough concentration (dose).
Paracelsus (Philip von Hohenheim),
“The Father of Toxicology” 11
November or 17 December 1493 24 September 1541
The concept of dose-response is central to determining "safe" and
"hazardous" levels and dosages for drugs, potential pollutants, and other
substances to which humans or other organisms are exposed. These
determinations are used in pharmaceutical drug development and are often the basis for public health
standards, which specify maximum acceptable concentrations of various contaminants in food, public
drinking water, and the environment.
For medicines in the development phase, doses are carefully determined so the appropriate response
will occur (i.e., treat the ailment and minimize negative side effects). This is why your medicine bottle
has clear instructions such as “take only 2 tablets every 6 hours and do not exceed 6 tablets in 24
hours.”
An important aspect of dose-response relationships is the concept of threshold. For most types of toxic
responses there is a dose, called a threshold, below which there are no adverse (bad) effects from
exposure to the chemical. The human body has defenses against many toxic agents. Cells in human
organs, especially in the liver and kidneys, break down chemicals into nontoxic substances that can be
eliminated from the body in urine and feces (the process is called metabolism, which was discussed in
the last edition of Pharmacology Corner). With this process, the human body can take some toxic insults
(at a dose that is below the threshold) and still remain healthy.
The identification of the threshold beyond which the human body cannot remain healthy depends on
the type of response that is measured and can vary depending on the individual being tested.
Thresholds based on acute responses, such as death or coma, are more easily determined, while
thresholds for chemicals that cause cancer or other chronic responses are harder to determine. Even so,
it is important for toxicologists to identify a level of exposure to a chemical at which there is no effect
and to determine thresholds when possible.
Dose-response relationships generally depend on the exposure time and route of administration, so
quantifying the response after a different exposure time or for a different route leads to a different
relationship and possibly different conclusions. This limitation is one reason why it sometimes takes
years to fully conduct dose-response studies on a single drug or chemical.
Next time in Pharmacology Corner we’ll discuss routes of administration. Do you know the difference
between parenteral and enteral?
Copyright © 2015 Aegis Sciences Corporation All Rights Reserved
Pharmacology Corner: Dose-Response
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Copyright © 2015 Aegis Sciences Corporation All Rights Reserved