Injected drugs will absorb at varying degrees according to tissue perfusion of the site. Intradermal drugs travel from the injection site into the capillaries more slowly than subcutaneously administered drugs. Drugs injected into the muscle will absorb even more quickly due to the abundant supply of blood to the muscles. Fat acts as a storage location for lipid-soluble drugs (like anticoagulants). Drugs may accumulate there, building up and remaining for an extended period, and releasing long after administration of the drug is complete. highly ionized drugs are unable to cross lipid membranes. Ion channels are selective porous passages in the cell membrane that allow ion movement in and out of the cell. Some drugs block these routes. Ability to cross barriers Certain areas of the body, like the brain and testis, are resistant to drug penetration because these tissues are lined with capillaries made of endothelial cells; these cells create a barrier between those tissues and the rest of the body (i.e., blood-brain barrier). This issue is of special concern in the case of pregnant women, as some drugs can cross the placenta, causing harm to the fetus, or may be passed on to an infant through the mother’s breast milk. Drugs administered orally must travel through a number of cell membrane barriers before reaching circulation. Binding Binding of the drug to other molecules in the blood and tissue limit its distribution to specific areas of the body. For example, drugs bound to plasma proteins are limited in that they can only travel where the proteins go. of clearance in different parts of the body. Clearance from the entire body, including all body tissues, is referred to as systemic clearance. Systemic clearance is made up of clearance from body organs, like the liver and kidney. Elimination from the body occurs in many organs. The two primary areas of drug elimination are the liver and kidneys. Little change occurs to the drug that is eliminated in urine, while biotransformation of the drug occurs when it is metabolized by the liver and excreted. as “saturable,” “capacity-limited elimination,” “dose- dependent” or “concentration dependent.” Graphically linear or “first order” kinetics, in contrast, refer to a rate of absorption that is typically proportional to the amount in the gastrointestinal concentration (gut) or drug concentration in the originating compartment. orally, so the active ingredients are utilized appropriately for therapeutic benefits rather than rendered inactive or used up through the liver’s metabolic properties. A number of interrelated factors influence an individual’s ability to metabolize drugs, including physical condition, genetic differences and age. In cases of liver disease or dysfunction, where there is destruction of hepatocytes, metabolic action will be disturbed or slowed. Reduced hepatic blood flow may also be a result of cardiac failure or shock.
to cross water barriers between cells. Some substances may increase or decrease the drug’s absorption. Grapefruit juice, for example, enhances drug absorption. Drugs are typically absorbed less efficiently through skin or mucous membranes than oral or parenteral routes. The rate of rectal and sublingual absorption is relatively rapid due to the abundant blood supply available to the mucosal surfaces. Liquid medicines are absorbed more quickly than solid preparations. Lipid-soluble drugs are absorbed quickly, while enteric coatings slow absorption. Drug distribution Distribution involves movement of the drug from the administration site to the area targeted for a specific desired effect of the drug. Distribution of drug molecules depends on many interrelated factors, including blood flow, binding of the drug and barriers between body compartments. Some drug molecules are deposited in storage areas along the route, and some are rendered inactive or never distributed. Tissue with the most abundant blood flow tends to receive the drug first; increased blood flow to the tissue means increased uptake of a drug. Tissues receiving the most blood, like the brain and kidney, have the highest rate of uptake, while tissues with low blood supply, like fat, accumulate the drug at a slower rate. Highly vascular organs like the liver, kidney and heart will acquire the drug more quickly than bone, muscle, fat or skin tissues, which have low vascularity. Other characteristics of the individual, including activity level and tissue temperature, can also affect the drug’s distribution to the skin and muscle. Lipid-solubility and the degree of ionization Solubility refers to the drug’s ability to enter tissues; highly lipid-soluble drugs can travel throughout the body, while Volume of distribution and clearance Volume of distribution refers to the amount of the drug in the body divided by the concentration of the drug in blood or plasma. The volume of distribution can be discussed in terms of blood, plasma or water (also referred to as “unbound”). Drug clearance refers to its elimination from the body tissues. Clearance describes the rate of elimination divided by the drug concentration. Clearance, like volume of distribution, can be referred to in terms of blood, plasma or unbound in water. Total clearance may be composed of many different kinds or processes
Rate of absorption: Zero order and first order elimination The rate of absorption is largely dictated by the route of administration and drug composition. Drug absorption can be referred to as graphically “nonlinear” or “zero-order” when the rate of drug release is not associated with the amount of drug remaining in the originating compartment; for example, in the case of a time-released drug. A model that exhibits this characteristic may also be referred to
First-pass effect After the drug is absorbed across the gut wall, the drug is delivered by blood to the liver before it reaches systemic circulation. Drugs can be metabolically processed by the gut wall as well as the blood, but typically, it is the liver that is responsible for most metabolism before the drug enters systemic circulation. The liver may also excrete the drug in bile. Each of these channels may contribute to the loss in bioavailability, the sum of which is referred to as first-pass effect or elimination . This means that a drug is swallowed and absorbed with its effects diminished through processing by the liver. Because of this effect, some types of medications are administered intravenously rather than
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Book Code: MIL1224
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