1.4 Distribution
Distribution
The second stage of pharmacokinetics is the process known as distribution. Distribution is the process by which a drug is dispersed throughout the body’s blood and tissues. After a drug enters into systemic circulation by absorption or direct administration, it will pass from vascular spaces to tissues where a drug-receptor interaction will occur, creating the effect of the drug.
Drugs are designed to primarily cause one effect, meaning they bind more strongly to one specific receptor site and predictably cause or block an action. However, side effects and adverse effects can occur when the drug binds to other sites in addition to the target tissue, causing an unintended action. These side effects can range from tolerable to unacceptable and can result in the discontinuation of the medication. For example, a person might take the pain reliever ibuprofen (Advil) to treat a sore leg muscle, and the pain may be subsequently relieved, but there may also be stomach irritation as a side effect.
The distribution of a drug throughout the body is dependent on many body-related factors such as blood flow, tissue differences, plasma protein-binding, the blood-brain barrier, and the placental barrier.
Blood Flow
The circulatory system transports medications throughout the body in the bloodstream. Many factors can affect the blood flow and delivery of medication, such as decreased blood flow (due to dehydration), blocked vessels (due to atherosclerosis), constricted vessels (due to uncontrolled hypertension), or weakened pumping by the heart muscle (due to heart failure). As an example, when administering an antibiotic to a client with diabetes who has an infected toe, it may be difficult for the antibiotic to move through the blood vessels all the way to the area of the toe that is infected because of blocked vessels in the legs and feet due to atherosclerosis.
Tissue Differences
Distribution occurs most rapidly into tissues with a greater number of blood vessels that allow high blood flow (such as the lungs, kidneys, liver, brain). Distribution occurs least rapidly in tissues with fewer numbers of blood vessels (such as fat), resulting in low blood flow. However, lipophilic drugs (i.e., drugs that dissolve in lipid environments) disproportionately distribute into adipose tissue in obese subjects.
The permeability of capillaries is tissue-dependent. Capillaries of the liver and kidney are porous, allowing for greater permeability. Distribution rates are relatively slower or nonexistent into the central nervous system because of the tight junction between capillary endothelial cells and the blood-brain barrier.
Protein-Binding
After a drug enters the bloodstream, a portion of it exists as free drug, dissolved in plasma water, but a portion of it becomes bound to proteins. This is important because only free and unbound drugs will pass from the bloodstream to tissues where drug-receptor interactions will occur, thus producing the