Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics.pdf

Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics Key Points Once a drug is administered, it goes through two phases, the pharmacokinetic phase and the pharmacodynamic phase. The pharmacokinetic phase describes the movement of the drug through the body. The pharmacokinetic phase is composed o...

Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics Key Points Once a drug is administered, it goes through two phases, the pharmacokinetic phase and the pharmacodynamic phase. The pharmacokinetic phase describes the movement of the drug through the body. The pharmacokinetic phase is composed of four processes: (1) absorption, (2) distribution, (3) metabolism, and (4) excretion. Drug absorption is the movement of the drug into the bloodstream after administration. For the body to utilize drugs taken orally, a drug in solid form must disintegrate into small particles and combine with a liquid to form a solution, a process known as dissolution; this enables the drug to be absorbed from the gastrointestinal tract into the bloodstream. Absorption across the mucosal lining of the small intestine occurs through passive transport, active transport, or pinocytosis. Passive transport occurs through two processes, diffusion and facilitated diffusion. o In diffusion, drugs move across the cell membrane from an area of higher concentration to one of lower concentration. o Facilitated diffusion relies on a carrier protein to move the drug from an area of higher concentration to an area of lower concentration. Active transport requires a carrier, such as an enzyme or protein, to move the drug against a concentration gradient; energy is required for active absorption. Pinocytosis is a process by which cells carry a drug across their membrane by engulfing the drug particles in a vesicle. The mucous membrane that lines the GI tract is composed of lipids and protein; lipidsoluble drugs are able to pass rapidly through the mucous membrane. Water-soluble drugs need a carrier, either an enzyme or a protein, to pass through the mucous membrane. Large particles are able to pass through the mucous membrane if they are nonionized. Blood flow, pain, stress, hunger, fasting, food, and pH affect drug absorption. In the liver, some drugs are metabolized to an inactive form and are excreted, thus reducing the amount of active drug available to exert a pharmacologic effect; this is referred to as the first pass effect. Bioavailability refers to the percentage of administered drug available for activity. Factors that alter bioavailability include (1) the drug form, (2) route of administration, (3) GI mucosa and motility, (4) food and other drugs, and (5) changes in liver metabolism. Distribution is the movement of the drug from the circulation to body tissues. Drug distribution is influenced by vascular permeability and permeability of cell membranes, reginal blood flow and pH, cardiac output, tissue perfusion, the ability of the drug to bind tissue and plasma proteins, and the drugs lipid solubility. As drugs are distributed in the plasma, many are bound to varying degrees with protein; the portion of the drug that is bound is inactive because it is not available to receptors, and the portion that remains unbound is free, active drug. Copyright © 2021, Elsevier Inc. All Rights Reserved. Key Points 3-2 Metabolism, or biotransformation, is the process by which the body chemically changes drugs into a form that can be excreted. The liver is the primary site of metabolism. Liver enzymes—collectively referred to as the cytochrome P450 system, or the P450 system, of drug-metabolizing enzymes— convert drugs to metabolites. A prodrug is a compound that is metabolized into an active pharmacologic substance and are often designed to improve drug bioavailability. The drug half-life (t½) is the time it takes for the amount of drug in the body to be reduced by half. Metabolism and elimination affect the half-life of a drug. By knowing the half-life, the time it takes for a drug to reach a steady state can be determined; a steady state occurs when the amount of drug being administered is the same as the amount of drug being eliminated. A loading dose, a large initial dose that is significantly higher than maintenance dosing, allow the therapeutic effects to be obtained while a steady state is reached. The main route of drug elimination is through the kidneys. Prerenal, intrarenal, and postrenal conditions affect drug excretion. o Prerenal conditions reduce blood flow to the kidney and result in decreased glomerular filtration. o Intrarenal conditions affect glomerular filtration and tubular secretion and reabsorption. o Postrenal conditions that obstruct urine flow adversely affect glomerular filtration. Common tests used to determine renal function include creatinine and blood urea nitrogen (BUN). It is important for nurses to know their patient’s kidney function to ensure correct drug dosage. Pharmacodynamics is the study of the effects of drugs on the body; drugs act within the body to mimic the actions of the body’s own chemical messengers. The dose–response relationship is the body’s physiologic response to changes in drug concentration at the site of action. Potency refers to the amount of drug needed to elicit a specific physiologic response to a drug. The point at which increasing a drug’s dosage no longer increases the desired therapeutic response is referred to as maximal efficacy. The therapeutic index describes the relationship between the therapeutic dose of a drug (ED50) and the toxic dose of a drug (TD50). The therapeutic range (also known as the therapeutic window) is a range of doses that produce a therapeutic response without causing significant adverse effect in patients. Onset is the time it takes for a drug to reach the minimum effective concentration (MEC) after administration. A drug’s peak occurs when it reaches its highest concentration in the blood. Duration of action is the length of time the drug exerts a therapeutic effect. Drugs act by binding to receptors; binding of the drug may activate a receptor, producing a response, or it may inactivate a receptor, blocking a response. Copyright © 2021, Elsevier Inc. All Rights Reserved. Key Points 3-3 Most receptors, which are protein in nature, are found in cell membranes. There are four receptor families: (1) cell membrane–embedded enzymes, (2) ligand-gated ion channels, (3) G protein–coupled receptor systems, and (4) transcription factors. Drugs that activate receptors and produce a desired response are called agonists. Partial agonists are drugs that elicit only moderate activity when binding to receptors; partial agonists also prevent receptor activation by other drugs. Drugs that prevent receptor activation and block a response are called antagonists. Drugs that affect multiple receptor sites are considered nonspecific; drugs that affect multiple receptors are considered nonselective. Mechanisms of drug action include (1) stimulation, (2) depression, (3) irritation, (4) replacement, (5) cytotoxic action, (6) antimicrobial action, and (7) modification of immune status. Side effects are secondary effects of drug therapy; all drugs have side effects. Adverse drug reactions are unintentional, unexpected reactions to drug therapy that occur at normal drug dosages. Drug toxicity occurs when drug levels exceed the therapeutic range; toxicity may occur secondary to overdose (intentional or unintentional) or drug accumulation. Pharmacogenetics refers to the study of genetic factors that influence an individual’s response to a specific drug. Genetic factors can alter drug metabolism, resulting in either enhanced or diminished drug response. Tolerance refers to a decreased responsiveness to a drug over the course of therapy; an individual with drug tolerance requires a higher dosage of drug to achieve the same therapeutic response. Placebo effect is a drug response not attributed to the chemical properties of the drug; the response can be positive or negative and may be influenced by the beliefs, attitudes, and expectations of the patient. A drug interaction is defined as an altered or modified action or effect of a drug as a result of interaction with one or multiple drugs. Pharmacokinetic interactions are changes that occur in the absorption, distribution, metabolism, and excretion of one or more drugs. Pharmacodynamic interactions are those that result in additive, synergistic, or antagonistic drug effects. Food may increase, decrease, or delay the body’s pharmacokinetic response to drugs. Drugs often interfere with clinical laboratory testing by cross-reaction with antibodies, interference with enzyme reactions, or alteration of chemical reactions. A drug-induced photosensitivity reaction is a skin reaction caused by exposure to sunlight; it is caused most often by the interaction of a drug and exposure to ultraviolet A (UVA) light. Copyright © 2021, Elsevier Inc. All Rights Reserved.