Contributors:Anuj Paul, Nancy Hutnik RN, BSN, Elizabeth Nixon-Shapiro, MSMI, CMI, Alaina Mueller, Evan Debevec-McKenney
Pharmacokinetics refers to the movement and modification of a medication inside the body. Once a 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 Elimination.
Now, we’re going to focus on the second step of pharmacokinetics, so distribution, which refers to the process of how an absorbed medication moves from the bloodstream to body tissues. Now, each organ and body tissue receives different amounts of medications; and the rate of the distribution - or how quickly this process occurs - as well as the extent of the distribution - or how much of that medication reaches a body tissue - can be affected by several factors.
One such factor is blood supply to different tissues. Μedications are more rapidly distributed to body tissues that receive large amounts of blood supply, like the brain, liver, kidneys, and spleen; and less rapidly to the tissues with lower blood supply, like the GI tract, skin, adipose tissue, and bones.
However, some tissues like the brain have an additional filter or barrier, known as the blood-brain barrier, which is a highly selective membrane that strictly regulates which substances are able to cross. The blood-brain barrier consists of tight junctions that seal off the endothelial cells lining the capillaries in the brain. In addition, the blood-brain barrier is surrounded by a basement membrane and astrocytes, which further strengthen it. As a result, the blood-brain barrier is able to prevent the entry of large, water-soluble molecules or pathogens that are floating around in the blood, while letting in water, oxygen, glucose, and smaller, lipid-soluble molecules.
Similarly, the size and polarity of a medication affects its distribution; so in general, smaller, hydrophobic or lipid-soluble medications can easily cross through the lipid bilayer cell membranes, giving them an extra edge in distribution over large, hydrophilic or water-soluble medications.
Another factor affecting distribution is the degree of plasma protein binding. Medications travel through the bloodstream partly bound to plasma proteins, like albumin, and partly unbound or free. But only the unbound fraction is free to diffuse into tissues, whereas medication molecules that are bound to plasma proteins remain limited to the plasma. That’s why medications with lower plasma protein binding, such as gentamicin, get distributed readily in the tissues, while medications with higher plasma protein binding, such as warfarin, take much more time to free themselves and diffuse, thus giving them a longer duration of action.
All right, now, before administering any medication to your client, be sure to keep in mind the general pharmacokinetic principles that relate to how medication is distributed within the body. First, review your client’s medical history, taking note of any conditions that can affect medication distribution; these conditions include liver disorders, such as hepatitis or cirrhosis, which could decrease the production of albumin and other plasma proteins; as well as renal disorders like nephrotic syndrome, which causes proteinuria and loss of plasma proteins; and finally, conditions that affect tissue perfusion, like vascular changes that can occur with diabetes. Lastly, review your client’s most recent laboratory test results, with a focus on renal and liver function tests, as well as serum albumin.