Complete Your CE Test Online - Click Here including creams, gels, plasters and patches, as well as sprays, powders and suppositories. Transdermal medications are applied to the skin for systemic effect. They typically take the form of patches that stick to the skin, and may be worn for a period of hours or days. Orally administered medications, which are taken by mouth, may be in the form of a solid pill, tablet, capsule or lozenge, but may also be powder or granular in form. Orally administered preparations also take the form of liquids and may be referred to as solutions, emulsions, syrups or tinctures, among other names. Oral medication is convenient, but may be slower and less complete than dosage through parenteral (non-oral) channels. Solid medication must be dissolved and withstand exposure to stomach acid. Additionally, oral medications are subject to metabolism by the gut and liver before reaching circulation (first-pass effect). Sublingual medications are directly absorbed into systemic venous circulation, avoiding first-pass effect. The absorption can vary from fast to slow, according to the composition of the drug. Inhalation drugs are commonly used for respiratory diseases, as this method brings the drug into close contact with the target organ (the lungs). Suppositories are also directly absorbed into systemic venous circulation. This method allows for the absorption of larger doses of a drug and may be useful for patients who cannot use sublingual or orally administered medication. Some drugs are administered parenterally, meaning they enter the body through a route other than the alimentary (gastrointestinal) tract. Parenteral administration includes injection or infusion of a sterile preparation into the tissue, and includes the use of subcutaneous, intramuscular, intravenous, intrathecal and intra-articular routes. Intravenous administration introduces the drug into systemic circulation immediately and provides complete absorption. Both intramuscular and subcutaneous administrations allow faster and more complete absorption than oral administration, although subcutaneous administration is slower than intramuscular methods. Intramuscular injections tend to be more painful than subcutaneous injections, but facilitate larger dosages of the drug, which are not possible in subcutaneous administration. Drug-body interaction It is sometimes said that pharmacokinetics is the study of what the body does to a drug, while pharmacodynamics is the study of what a drug does to the body. Therapeutic drug administration attempts to achieve the desired beneficial effect of the drug with minimum negative, or adverse, effects. The dose-effect relationship can be separated into pharmacokinetic (dose-concentration) and pharmacodynamic (concentration-effect) portions. Concentration is the link between pharmacokinetics and pharmacodynamics. The three main processes of pharmacokinetics are absorption, distribution and elimination. See figure below (Masters & Trevor, 2012): Pharmacokinetics Pharmacokinetics refers to the movement of drugs within the body and its effects, often in relation to a specific time-frame. Once a drug is administered though one of the routes discussed above, it is absorbed, distributed, metabolized and excreted by the body. Many factors, including the drug’s composition, the dose and the health or condition of the client, determine the therapeutic value of the drug and manner and the timing in which it undergoes absorption, distribution, metabolism and excretion. The administration route is chosen for its convenience as well as the associated bioavailability. Hepatic first-pass effect can be avoided by using inhaled drugs, under-the-tongue tablets or transdermal administration, all of which bring the drug into systemic circulation through a vascular network. Drugs administered through rectal suppositories avoid hepatic first-pass effect to a lesser degree than either transdermal or sublingual administration, with about half of the drugs absorbed through vessels that empty into the inferior vena cava; the other half of the rectal dose moves into an area where veins feed into the liver. Measurements of drug concentrations may be taken by invasive methods (blood or spinal fluid, for example) or non-invasive methods, as in the case of urine, feces or saliva samples. The concentration of the drug in plasma (the liquid portion of blood) serves as a reference point for the amount of drug in the body’s compartments because the drug is fairly evenly distributed and can be sampled fairly easily. Plasma is in constant contact with body tissues as it distributes the blood to body compartments. Plasma concentration is measured by taking a sample of blood. Principles of permeation A drug must be absorbed into the blood from its administration site and distributed to its target action site. To do this, the drug must permeate through the barriers that separate the compartments of the body. These barriers include the tissues that make up the intestinal walls, capillaries that line the gut, and the blood-brain barrier – the walls of the capillaries bordering the brain. Drug permeation takes the form of four main mechanisms: ● ● Aqueous diffusion. ● ● Lipid diffusion. ● ● Special carriers. ● ● Endocytosis and exocytosis. Aqueous diffusion occurs within compartments of the body (called aqueous compartments) and across certain membranes with porous linings. Most drugs are prohibited from passing through special barriers, called lipid barriers, which separate aqueous compartments of the body. Where the lipid partitions and aqueous compartments border one another, the drug molecule will move from one compartment to another in a predictable way, depending on properties of the chemical and each compartment. Special carrier molecules are able to carry substances necessary for cell function but too large or insoluble to pass through lipid barriers. Very large substances that are unable to pass though barriers, even with the help of special carriers, may use endocytosis, a process in which the substance is engulfed by the cell membrane, where it is broken down and released. The reverse of this process, exocytosis, causes the secretion of a substance from a cell. Compartments of the body Compartment models treat the body as a set of interconnected compartments: Within each compartment, the drug concentration (percentage of drug) is assumed to be evenly (homogenously) distributed, and movement of the drug between the compartments proceeds in a predictable way. Most drugs exhibit properties of multicompartment pharmacokinetics, meaning the drug accumulates and is eliminated from different compartments of the body at varying rates, resulting in different concentrations of the drug in different compartments of the body. The number of compartments in the simplest models typically includes a compartment associated with the administration route. If the release from dosage form is very fast, as is the case in IV injection or with use of a dissolved drug, no dosing compartment is included. Tissue compartments may include both normal and deep distribution (adapted from Vallabhaneni, 2014). Multi-compartment model Massage.EliteCME.com Page 37