Contributors:Mary Roberts MSN, RN, Anna Hernández, MD, Jung Hee Lee, MScBMC, Rachel Yancey, Alaina Mueller
Pharmacokinetics refers to the movement and modification of a drug or medication inside the body. So once the medication is administered, it first has to be absorbed into the circulation, then distributed to various tissues throughout the body, metabolized or broken down, and finally, eliminated or excreted in the urine or feces. This process can be broken down into four components with the acronym “ADME”, which stands for absorption, distribution, metabolism, and excretion.
In this video, we’re going to focus on metabolism, which refers to the conversion, or biotransformation, of a medication. In most cases, metabolic reactions act by turning an active medication into a less active metabolite, as well as turning lipid soluble medications into a more water soluble metabolite, which can be eliminated more easily from the body, mainly via the urine or feces. Some other medications, though, are administered in an inactive form, also known as a prodrug, that needs to be metabolized into its active form before it can be effective.
All right, now most metabolic reactions take place in the liver; although certain medications can be metabolized by other tissues and organs, including the lungs, kidneys, skin, and walls of the small intestine.
After a medication is taken orally, it is absorbed from the walls of the small intestine and transported into the liver via the portal vein. Once in the liver, hepatic enzymes work on the medication to metabolize it; this process is known as first-pass metabolism or first-pass effect, and is responsible for breaking down most medications, as well as converting certain prodrugs into their active metabolites. For example, enalapril, an ACE inhibitor used to treat hypertension, gets converted into its active metabolite, enalaprilat, in the liver. Similarly, codeine, a weak opioid, is converted by hepatic enzymes into morphine, which is more effective for pain management.
As a result of first-pass metabolism, certain medications that are highly metabolized by the liver can lose their effectiveness when taken orally, so alternative routes of administration must be used to achieve the desired therapeutic effect. Alternative routes include intravenous, intramuscular, transdermal, sublingual, or inhaled medications, which go straight into the systemic circulation and exert their effect before reaching the liver, so they are often more effective than the oral route. This is especially true for medications that undergo extensive first-pass metabolism, including morphine, diazepam, lidocaine, and nitroglycerin.
All right, now the liver’s main mechanism to metabolize medications is via a family of enzymes called cytochrome P450, or CYP450 for short. These enzymes are often abbreviated as CYP followed by a series of numbers and letters indicating the exact enzyme subtype. Each enzyme is involved in either activating or inactivating multiple medications, so if two medications are metabolized by the same enzyme, they can interfere with each other’s normal rate of metabolism.
In other cases, certain medications, foods, or supplements can induce or inhibit metabolic enzyme activity. When a substance increases the ability of an enzyme to break down a medication, the effects of that medication are decreased; whereas if a substance decreases enzyme activity, the effects and the risk of toxicity of that medication are increased. Examples of metabolic inducers include carbamazepine, rifampin, and St. John’s wort; while metabolic inhibitors include the antifungal fluconazole and grapefruit juice.
Additionally, because metabolic enzyme systems are only partially developed at birth, newborns may have some difficulty metabolizing certain medications. As people age, enzymatic activity also decreases, so elderly individuals may not be able to metabolize medications as well as children and younger clients. Also, since most metabolic reactions take place in the liver, chronic liver disease may lead to a decrease in enzyme activity.
Finally, there’s a huge variability in the rate of metabolic reactions as a result of genetic variability. Some clients, known as poor metabolizers, have fewer enzymes, or enzymes that work slower and less effectively against certain medications. In such cases, medications can build up in the body, resulting in dangerous side effects or toxicity.
On the other hand, there are rapid and ultra-rapid metabolizers, who inactivate medications so fast that it’s difficult to achieve therapeutic levels for certain medications. In such cases, clients may require larger doses than usual, or the use of an alternative medication.
Okay, before administering any medication to a client, keep in mind some of the general pharmacokinetic principles that relate to how the medication is metabolized in your client’s body. Begin by reviewing their medical history, taking note of conditions that could impact medication metabolism, such as cardiovascular, hepatic, or renal disease.