Principles of Pharmacology
1.4 Pharmacokinetics – Distribution
The second stage of pharmacokinetics is the process known as drug distribution. Distribution is the process by which medication is dispersed throughout the body via the bloodstream. Once a drug enters into systemic circulation by absorption or direct administration, it must be distributed into interstitial and intracellular fluids to get to the target cells. The distribution of a drug throughout the body is dependent on common factors such as blood flow, plasma protein binding, lipid solubility, the blood-brain barrier, and the placental barrier. Other factors include capillary permeability, differences between blood/tissue, and volume of distribution.
Distribution of a medication can also cause unintended adverse effects or side effects. 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 can occur when the drug binds to other sites in addition to the target tissue, causing secondary side effects. These side effects can range from tolerable to unacceptable resulting 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 that may cause the person to stop taking Ibuprofen.
Blood Flow
The blood stream carries medications to their destinations in the body. Many factors can affect the blood flow and delivery of medication, such as decreased 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 cells of the toe that is infected.
Once the drug is in the bloodstream, a portion of it may exist as free drug, dissolved in plasma water. Some of the drug will be reversibly taken up by red cells, and some will be reversibly bound to plasma proteins. For many drugs, the bound forms can account for 95-98% of the total. This is important because it is the free drug that traverses cell membranes and produces the desired effect. It is also important because a protein-bound drug can act as a reservoir that releases the drug slowly and thus prolongs its action. With drug distribution, it is important to consider both the amount of free drug that is readily available to tissues, as well as the potential drug reserve that may be released over time.
Protein-Binding
A common factor impacting distribution of medication is plasma protein in the blood. Albumin is one of the most important proteins in the blood. Albumin levels can be decreased by several factors such as malnutrition and l