How drugs work (Proceedings)


How drugs work (Proceedings)

Nov 01, 2010

The science of how drugs work on the body (or the microorganism or parasite) is pharmacodymanics (its counterpart being pharmacokinetics, how the body works on the drug). In this section, the basic concepts of drug concentration and drug action are followed by a review of the mechanisms of action of the major drug groups used in food animal practice including NSAIDs, glucocorticoids, reproductive drugs, antimicrobials, and parasiticides.

We assume that drug concentration is correlated with drug action; in other words, higher concentrations of drug in the blood stream are correlated with increased pharmacological response. Of course, there are limits to the increase, and drug response has been demonstrated in the majority of cases to occur in a sigmoid fashion, as shown in the graph below. This graph demonstrates the typical line when the log of drug concentrations is graphed against percent of maximal response. Typical response curves include an area of steep slope, in which there is proportional increase in response with increases in drug concentration. At some point close to maximal response, increasing drug concentrations do not result in significantly increased action of the drug. The dose at which the response is 50% of maximal is designated the median effective dose or the ED50. The ED50 is a useful way to compare drugs, and a way to evaluate changes in drug response.

While this graph is a useful way to gauge response to different doses, it does not tell us what is causing the drug response. Drugs cause a response in the animal or the parasite in a number of ways, with the classical way being the receptor-mediated response. Other ways drugs can act include effects on enzymes (inhibiting or activating), effects on ion channels in cell walls (some of which are also "receptors" of some sort), and other non-specific actions (such as drugs that merely replace endogenous compounds or drugs that change osmolarity).

Drugs Acting on Animal Cells

Mechanisms of Autonomic Drugs

Drugs commonly used in food animals that act through receptors include many of the autonomic drugs, such as xylazine (an alpha-2 agonist) and epinephrine. When these types of drugs interact with the receptor, a cascade of events is generally activated in the cell, resulting eventually in the desired pharmacological action (such as the sedation associated with xylazine, or the reversal of sedation associated with tolazoline). Xylazine and other alpha-2 agonists act by interacting with alpha-2 receptors on post-synaptic membranes, which are associated with inhibition of neurotransmission. Epinephrine acts on pre-synaptic alpha and beta receptors non-specifically, and causes among other things vasoconstriction and tachycardia.