5 anxiety disorders

PHARMACOLOGY 25However, if an individual is prescribed two or more medications that are eachhighly bound to the same carrier protein, then they could potentially compete forprotein binding. In fact, it is possible to saturate, or fill, the available carrier proteinbinding sites. When this occurs, the free fraction, that is, the non-protein-bound andbiologically active portion, of the medication might be larger than anticipated. Thiswill cause the medication to be more potent at lower doses. If the potential for thistype of drug interaction is anticipated in advance, then the doses can be adjustedaccordingly. However, if the protein-binding interaction comes as a surprise, complicationssuch as drug toxicity can arise. We’ll talk more about this in our discussionof drug–drug interactions later in this chapter.3. Exiting the Bloodstream. Medications, nutrients, and other substances arecontinuously leaving the bloodstream and entering other tissues or organs. They arefree to reenter the bloodstream at any time and often do. The effect of the medicationdepends on where it exits. If it exits at the liver, the body’s version of a wastetreatment and chemical detoxification facility, then the medication is likely to beinactivated, that is, metabolized. If it exits at the kidney, then it will likely beexcreted in urine. We’ll describe this in more detail in the next section.Of course, our main concern is how the medication leaves the bloodstream toenter the brain. The brain has a special mechanism called the blood–brain barrierthat protects it from many harmful substances that may be circulating in the bloodstream.The blood–brain barrier is comprised of several distinct components, bothstructural (e.g., tight junctions between the cells lining the capillaries in the brain)and biochemical (e.g., enzymes present on the blood vessel walls that inactivatevarious drugs). It is especially difficult for substances that dissolve in water to passthrough the fatty blood–brain barrier. To be able to traverse the blood–brain barrier,nearly all psychiatric medicines are slippery, fat-loving (lipophilic) substances thatcan readily slide through the barrier and enter the brain. The principal exception islithium, which dissolves in water but as an atom (rather than a big bulky molecule)is so small that it can nevertheless pass through the barrier. Once a psychiatricmedication has passed through the blood–brain barrier, it has reached its intendeddestination and can now begin to do its work.Medication Elimination System. Obviously, the medication cannot and shouldnot stay in the body indefinitely. The key organs in the system that deactivate chemicalsand eliminate wastes are the liver and kidney.Liver: Chemical Processing. For protection from dangerous accumulation of varioustoxins, the body has evolved methods to eliminate foreign substances. Potentiallyharmful chemicals can originate from myriad sources including foods, liquids, air,and, of course, medications. The liver’s role is to inactivate these chemicals and toconvert (metabolize) them to water-soluble forms (i.e., forms that dissolve in waterrather than fat), which can more easily be filtered and eliminated by the kidneys.To do this work, liver cells have an abundance of enzymes that inactivate thesechemicals either by cutting off (cleaving) pieces of the molecules or modifying the