The terms pharmacokinetics and pharmacodynamics are often confused or used interchangeably, but they are two distinct concepts. Pharmacodynamics examines how drugs affect the body—induce unconsciousness, relieve pain, increase blood pressure, etc. Pharmacokinetics is the study of how the body affects the drug—the process by which drugs are absorbed, distributed throughout the body, metabolized, and excreted from the body. The practice of anesthesia involves the administration of a large number of drugs that have a significant impact on patients’ physiology and behavior. These effects are influenced not only by dose, route, and timing of administration but also by each patient’s physiology and anatomy, as well as coexisting disease. This chapter introduces some of the more important concepts in pharmacokinetics.

In anesthesia, most drugs are given as intravenous (IV) injections, but they can also be given orally (PO, from Latin per os, or “by mouth”), inhaled into the lungs, or given by other numerous other routes (see Table 4.1).

Most drugs are delivered to their sites of action by the bloodstream. Therefore, the initial distribution and onset time of the drug will be determined by how long it takes the drug to get into the bloodstream. This depends on the route of administration. Drugs that are injected intravenously are delivered directly to the bloodstream (intravascular space, central compartment). Inhaled gases are rapidly absorbed into the bloodstream in the alveoli. Sublingual drugs, like nitroglycerin, are absorbed by the oral epithelium and then move quickly into the bloodstream (within seconds). Transdermal and oral routes are much slower. Drug patches must diffuse the drug out of the patch, through the skin (an excellent barrier to the outside world), through subcutaneous fat and fascial layers, and into the bloodstream, which usually takes hours.

The oral route has a unique set of obstacles that must be overcome before a drug can get to its target organs. A tablet of gabapentin must be dissolved by gastric fluid, move to the small intestine where it is absorbed, and then move through the epithelial layers to eventually diffuse into the bloodstream, taking roughly 30-60 minutes. Unlike most other tissues, the venous drainage of the gut does not go directly back to the heart. Instead, it flows into the portal circulation taking nutrients and drugs, which are absorbed from the gut, to the liver where they are processed. One of the main functions of the liver is to detoxify the blood, by chemically altering (metabolizing) foreign substances. Therefore, with oral administration, the liver can remove a portion of drug from the bloodstream before the drug ever makes its way to the systemic circulation and target organs. This is known as first pass clearance. Much of the drug can be lost not only to first pass clearance but also to other factors. Gastric contents are highly acidic and can chemically degrade the drug. Additionally, other compounds in the gut can bind to the drug and prevent its absorption by the small intestine. Absorption can be impaired if the patient’s gut does not work properly or has unusual anatomy. Because of all of these factors, the oral route of administration leads to decreased bioavailability, which is the fraction of drug that is distributed in the systemic circulation relative to the total amount of drug given. This is why IV and PO dosing of medications is usually very different.

Some drugs are delivered directly to their sites of action. Local anesthetics are injected subcutaneously to anesthetize the area around the injection site (local infiltration). They can be injected around a large nerve (nerve block) or
into the epidural space to anesthetize an entire limb or portion of the torso. They can be injected into the subarachnoid space (intrathecal space), where they will act directly on the nerves that make up the spinal cord. In these situations, the drug remains where it was injected in order to work. It is also important to know that some drugs have multiple uses and multiple sites of action. Lidocaine is a local anesthetic that can be injected for local infiltration or nerve blocks. It is also frequently given intravenously to anesthetize the vein and reduce the pain on injection of induction agents. It can also be given intravenously to treat cardiac arrhythmias or chronic pain.