Pharmacotherapeutics, pharmacokinetics, and pharmacodynamics

• Pharmacotherapeutics is the clinical purpose or indication for giving a drug. • Pharmacokinetics is the effect of the body on the drug. It is made up of four phases: absorption, distribution, metabolism, and excretion. Absorption is the movement of the drug from the site of administration into the bloodstream. Distribution is movement of the drug through the bloodstream and eventually into the cells. Metabolism refers to the changing of the drug into another substance or substances (i.e., metabolites). Excretion is the removal of the drug or its metabolites from the body. Metabolism and excretion are considered together as elimination of a drug. Most commonly in practice, however, the clinician uses the term elimination as a synonym excretion. • The blood-brain barrier is the body's natural defense to keep toxins and poisons from reaching the brain. It also may prevent the distribution of needed drug molecules from reaching their target. • Drugs have different affi nities for protein molecules, especially albumin, in the blood. Drugs that are highly protein bound have a lower proportion of their molecules available to produce the desired therapeutic effect. Only the free drug is active. • Metabolism of drugs occurs primarily in the liver. Liver metabolism is predominantly achieved by specifi c liver enzymes, known as the P-450 system. The P-450 system also metabolizes some drug in the small intestine. Some drugs can induce this system, increasing their own or other drugs' metabolism. When multiple drugs are metabolized by the same P-450 family, the metabolism of all the drugs is normally decreased. Anything that impairs liver functioning also decreases drug metabolism. Decreased metabolism leads to increased circulating levels of the drug, more therapeutic effect, and possibly more adverse effects. • Drugs that are administered orally pass through the liver before going to the general circulation. If the drug is highly metabolized, a high fi rst-pass effect occurs. This effect substantially decreases the amount of drug that is distributed to the body. • The kidney is the primary organ responsible for drug excretion. There are three processes that affect the excretion of drugs in the urine: glomerular fi ltration, passive tubular reabsorption, and active tubular secretion. Anything that decreases kidney function decreases drug excretion, leading to increased circulating blood levels of the drug. • Half-life of a drug is the amount of time needed to eliminate (by metabolism and excretion) half of the drug molecules currently in the body. • Steady state is when the continuing dose of a drug is in balance with the elimination rate of the drug, that is, when the amount of drug entering the body equals the amount being removed. Steady state is achieved after four to fi ve half-lives. Achievement of steady state is not related to the dosage of the drug or the frequency of drug administration. • Most drugs create their effects in the body by attaching to special sites, called receptors, on cells. At the receptor site, the drug is able to stimulate the cell to act in a way that the cell is designed to act. Drugs that stimulate the cell to act are known as agonists. Drugs that attach to receptors to prevent other substances from attaching and "turning on" the cell are called antagonists or blockers. • The single occupancy theory and the modifi ed occupancy theory help to explain how drugs achieve their effects at receptors. • Potency of a drug refers to how much of a drug is needed to create the desired therapeutic effect. Effi cacy of a drug refers to how well the drug creates the desired therapeutic effect. Drugs may have different potencies but the same effi cacy. Effi cacy is a more important consideration than potency when selecting a particular drug. • Loading doses are larger-than-normal doses used when therapy is initiated with drugs that have very long halflives. The purpose of the loading dose is to achieve quickly a blood level of the drug that is in therapeutic range even though the drug has not reached steady state. • Maintenance doses are the doses administered regularly throughout therapy. • The therapeutic index is a measurement of the safety of the drug. Drugs that are described as having a narrow therapeutic index do not have much difference between the effective dose and the toxic or lethal dose. Patients receiving these drugs need to be monitored very closely for adverse effects. They also need to have their drug blood levels monitored closely. • Drug dosages are adjusted to maintain a therapeutic level of the drug. Drug blood levels are one way of determining whether a dose needs to be either increased or decreased.