A. Pharmacology and Drug Actions

Pharmacology is the study of drugs and their effects. A drug is a substance or chemical agent which can affect living processes – and can be a natural product, chemical substance, or pharmaceutical preparation for administration to a human or animal. Most drugs are used to treat the sick or a health condition; thus, pharmacology is a part of the broad science of medicine^[1]. More broadly, pharmacology is concerned with the mode of action of drugs on the human body, and the use of drugs in therapies. (Not to be confused with pharmacy – the science and profession concerned with preparing, storing, dispensing and proper use of drug products). Toxicology is the branch of pharmacology that generally deals with the undesirable effects of drugs on biological processes^[2].

Pharmacology includes two main subdivisions: pharmacokinetics and pharmacodynamics.

Pharmacokinetics describes what the body does to the drug. In order for a drug to “work”, it must enter the body and somehow reach a site of action. In most cases the site of action is a receptor located in a target tissue.^[3] A receptor is a cellular bound or unbound macromolecule with structural specificity. When a receptor becomes bound or activated by a drug, it undergoes a conformational change that alone or through a series of chain reactions can manifest an effect.^[4] A drug effect could be increasing of a secretion, a change in metabolism, inhibition of an enzyme, and so on.

Pharmacokinetics is concerned with processes that bring about changes in drug plasma concentration and the concentration of drugs in tissues over time. The concentration of any given drug will fluctuate according to the rates of four processes: absorption, distribution, metabolism and excretion; thus, interactions with nutrients may involve enzymes and transporters that are implicated in any of these processes.^[5]

Pharmacodynamics describes what the drug does to the body, and involves the study of the actions of drugs on target receptors and tissues. As mentioned above, the majority of drugs bind to specific receptors on the surface or interior of cells; however, there are other cellular components and non-specific sites which can serve as sites of drug action. Hydrogen and metal ions, enzymes, nucleic acids or macromolecular receptors can also be drug targets.^[6]

Drug Plasma Concentration Curves

Following oral drug administration, plasma concentration typically increases over time. A standardized drug plasma concentration curve is shown in Figure 1.1 A below.  In Figure 1.1, the y-axis is a linear scale of drug plasma concentration, often expressed in micrograms per milliliter or milligrams per liter, and the x-axis is a scale of time, usually expressed in hours. The maximal plasma drug concentration for a single dose of a drug given orally is known as maximum concentration (Cmax) and the time to time necessary to reach the Cmax is known as the Tmax, see Panel A.^[7]

Figure 1.1. Plasma drug concentration and drug bioavailability^[8]

Drug plasma concentration curves help us understand concepts such as bioavailability, which is defined as the fraction (f, in Figure 1.1.B) of the administered dose of a drug that reaches the systemic circulation in an active form. By definition, an intravenously administered drug has 100% bioavailability. The oral availability of a drug is determined by dividing the AUC of an orally administered dose of the drug (AUCoral) by the AUC of an intravenously administered dose of the same drug (AUCIV).^[9]