Two terms you are most likely familiar with are pharmacokinetics and pharmacodynamics. Pharmacokinetics is the study of the action of medications in the body, including the processes of absorption, distribution, metabolism, and elimination. An easy way to remember pharmacokinetics is what the body does to a medication. Pharmacodynamics is the study of the biochemical and physiologic effects of drugs on the function of living organisms and of their component parts. An easy way to remember pharmacodynamics is what the medication does to the body. This post will focus on pharmacokinetics
In the following paragraphs, I will break down each phase of pharmacokinetics with some key attributes to remember. Keep in mind this is not exclusive to medication and pharmacokinetics can include any substance taken up by the human body.
Absorption can be defined as the movement of a substance from the site of administration into the bloodstream. This includes how much of a substance there is and the rate it leaves the site of administration. The most common route medications are taken are by mouth but medications can be given intramuscularly, intravenously, intranasally, rectally, among other routes. Once a medication is given, it travels throughout the body. Substances taken by mouth must be absorbed into general circulation. For substances to have an effect, their molecules pass through cell membranes. This can happen by crossing through pores and channels or through a transport system due to lipid solubility. The majority of medications are too large to do this, including most psychotropic medications. The majority of these medications are absorbed due to their high lipid solubility. As medications pass through the liver, many are metabolized. This process is known as first-pass metabolism. The amount of medication that reaches the body’s circulation is known as bioavailability. Medication or drug bioavailability refers to the percentage of a substance that is absorbed and available to reach the target tissues. Substances administered intravenously have 100% bioavailability. Substances administered by other routes, such as by mouth, have lower bioavailability due to incomplete absorption and first-pass metabolism.
Distribution is movement of absorbed drug present in body fluids that is distributed throughout the body to target tissues. A requirement for distribution is adequate blood supply. For this reason, medications are distributed to areas of high blood flow first. This process can take place passively or actively and requires transport systems.
Lipid soluble molecules of medications pass through the cell membrane of capillaries or go between the endothelial cells. Medications with water-soluble molecules can only pass-through gaps between cells.
Capillaries in the brain do not have gaps between the cells, as these gaps are referred to as tight junctions.
Volume of distribution is the amount of drug that sequesters in adipose tissue. The more adipose tissue a person has, the greater the volume of distribution. Likewise, the more lipid soluble the drug, the greater the volume of distribution. Medications that are highly lipid soluble tend to have a high volume of distribution. This pharmacokinetic variable accounts for a longer half-life for many psychotropic medications, especially in women.
Another important component of distribution is protein binding. In circulation, medications bind to proteins. Unbound medication is known as free drug, which is active drug. Medications exist in both bound and unbound states. Medications travel when bound and cross membranes when
unbound. Drugs that are highly protein bound, the ratio of bound drug usually remains stable. When a patient has low plasma proteins, such as someone with low albumin, there will be more free drug in circulation. Drugs that are bound cannot exit the blood stream cannot have a pharmacologic effect, cannot be metabolized in the liver, and cannot be excreted.
There are a finite number of plasma proteins that compete and displace each other, which results in more free drug to bind to sites. This increases the risk of toxicity. Another point of consideration for protein binding has to do with tissue protein binding. Drugs that are lipid-soluble have a high affinity for adipose tissue, which has low blood flow. Some medications, such as tetracyclines, have affinity for bone.
The blood-brain barrier by design is relatively impenetrable and is protective. Only drugs that are lipophilic can cross. This is unlike the placental barrier in a pregnant woman, as many drugs pass. Medications with low molecular weight pass easiest.
Metabolism is the next phase of pharmacokinetics. Metabolism refers to the chemical inactivation (or activation in the case of a prodrug) of a drug through conversion to a more water-soluble compound that can be excreted from the body. This is known as biotransformation which is a chemical change of drug structure to enhance excretion, inactivate the drug, increase therapeutic action, and in turn decrease (or increase) toxicity. Medications can undergo two types of chemical reactions in the liver. Phase I metabolism includes oxidation, hydrolysis, or reduction to increase water solubility of drug molecules. This includes the cytochrome P450 enzyme system. Phase II metabolism includes conjunction or union of a drug molecule with a water-soluble substance.
The cytochrome P450 enzyme system operates throughout the body and is concentrated in the liver, intestine, and lungs. The P450 enzyme system is not the same in every individual and genetic polymorphisms can be present. This is something I will discuss in further detail in a future post. For now, be aware the system does not work the same for every individual and gender and racial differences play a part in this complex system.
To understand the way medications work in the CYP450 system, it is important you know the difference between a substrate, inducer, and inhibitor. A substrate is a drug that is affected by a change in its enzyme metabolism. An inducer is a drug that causes acceleration in the enzyme metabolizing another drug. An inhibitor is a drug that causes inhibition in the enzyme metabolizing another drug.
Finally, excretion or elimination refers to the process by which drugs and their metabolites are removed from the body. This most commonly occurs in the liver, kidneys, or colon. Elimination occurs because lipid soluble molecules have been changed to water-soluble molecules by the metabolic process. If not for this process, some drugs are so highly lipid soluble that it would take many years to rid the body of the drug.
All and all, understanding pharmacokinetics is a crucial part of pharmacology and whether you are learning to administer medications or prescribe them, this concept is crucial to understanding. In a later post, we will give a closer look to pharmacodynamics.
This post was written by Richard Gray, MSN, APRN, PMHNP-BC. The above information is for educational/entertainment purposes and is not intended to be treated as medical advice. If you have questions about a medication you are taking, discuss these questions with your medical provider.