Pharmacokinetics

Pharmacokinetics refers to the movement and modification of a medication inside the body, and involves absorption, distribution, metabolism, and excretion. Because nurses are licensed to administer medications, they must ensure patient safety by understanding pharmacokinetic principles of every medication they administer. The first step of pharmacokinetics is absorption, or the movement of a medication from the site of administration into the bloodstream. Now, the rate of absorption, or how quickly this process occurs, as well as the extent of the absorption, or how much of the medication reaches the bloodstream, can be affected by several factors.
One factor is the pH of the environment where absorption takes place. Since most medications are either weak acids or weak bases, weakly acidic medications are better absorbed in an acidic environment, like the proximal duodenum, while weakly basic medications are better absorbed in an alkaline environment, like the distal ileum.
Another factor is the route of administration. For instance, a medication given sublingually has a higher rate and extent of absorption than its oral form because the medication is easily absorbed through the thin epithelium into circulation without having to go through the gastrointestinal system. Lastly, food in the stomach can either slow down or promote absorption, depending on the medication. The second step is distribution, or movement of the medication from the bloodstream to the tissues and into the cells. One factor affecting distribution is blood supply to the tissues. Medications are more rapidly distributed to tissues receiving an ample blood supply, like the brain, liver, and kidneys; and less rapidly distributed to tissues with lower blood supply, like the skin, adipose tissue, and bones. Another factor affecting distribution is protein binding. Medications travel through the bloodstream partly bound to plasma proteins, like albumin, and partly unbound or free. But only the unbound medication can diffuse into tissues, whereas medication bound to albumin remains in the plasma. That’s why medications with lower plasma protein binding, such as gentamicin, get distributed readily to the tissues, while medications with higher plasma protein binding, like warfarin, take much more time to free themselves and diffuse into the tissues.
A medication’s ability to cross cell membranes and enter cells also affects distribution. The brain, for example, has an additional barrier, known as the blood-brain barrier, which is a highly selective membrane consisting of tight junctions that seal off the endothelial cells lining the capillaries in the brain. This barrier prevents the entry of large, water-soluble molecules like penicillin, while letting in lipid-soluble medications like phenobarbital. The third step is metabolism, also called biotransformation, where the body changes medications into a form that’s more easily excreted.
Now, metabolism mostly occurs in the liver, so, after a medication is ingested orally, it’s absorbed in the gastrointestinal tract and then transported by the hepatic portal vein to the liver. Once in the liver, hepatic enzymes, called cytochrome P450, or CYP450 for short, metabolize the medication, a process known as first-pass metabolism or the first-pass effect, which is responsible for breaking down most medications, as well as converting certain medications into their active metabolites. For example, enalapril, an ACE inhibitor used to treat hypertension, gets converted into its active metabolite, enalaprilat, in the liver.
Then, there are other medications, like morphine and nitroglycerin, that are so highly metabolized by the liver they lose their effectiveness when taken orally. In this situation, alternative routes of administration are used to achieve the desired therapeutic effect, like intravenous, transdermal, or sublingual, so the medication can go straight into the systemic circulation and exert its effect before reaching the liver.