NAPSR/CNPR Exam Combo Study Guide with CNPR All Chapters Latest 2025

Office of inspector General (OIG) - an arm of the department of Health and Human Services, which investigates regulatory infractions, provides compliance advice, and brings enforcement actions Federal Trade Commission (FTC) - Regulates general business practices to protect consumers against anti-competitive behavior and misleading claims Drug Enforcement Administration (DEA) - Regulates the distribution and use of narcotics and other controlled substances Antibodies - are proteins made by the body's immune system to bind and to neutralize foreign invaders. Monoclonal Antibodies - antibodies used against breast cancer and non-Hodkin's lymphoma, are created in laboratories to target the immune system of patients to specifically kill cancer cells Passive Diffusion - Diffusion is the random movement of molecules in fluid. Because of the lipid bilayer construction of the membrane, non-polar (lipid soluble) molecules are able to diffuse and penetrate the cell membrane. Polar molecules, however, cannot penetrate cell membrane readily via passive diffusion and rely on other transport mechanisms. Facilitated Diffusion - Polar drug molecules have been observed to cross cell membranes. The transport mechanism is via carrier systems. Transmembrane carriers, such as proteins, are similar to receptors and bind polar and non-polar drug molecules. They facilitate the diffusion of drugs across the cell membrane. This diffusion is from a region of high concentration to low concentration. Active Transport - the mechanism requires energy to drive the transportation of drugs against the concentration gradients, from low to high. The transportation rate is dependent on the availability of carriers and energy supply via a number of biological pathways. Pinocytosis - involves the engulfing of fluids by a cell. The process commences with the infolding of cell membrane around fluids containing the drug. The membrane then fuses and forms a vesicle with fluid core. In this way, the drug is taken into the cell interior within the vesicle. First Pass Metabolism - Drug absorbed through the gastrointestinal tract pass into the hepatic portal vein, which drains into the liver. The liver metabolizes the drug, which leads to reduction in the availability of the drug for interaction with receptors NAPSR/CNPR Exam Combo Study Guide with CNPR All Chapters Latest 2025 Blood-brain barrier - Due to this, distribution of drugs to the brain tissue is restricted for some types of drugs. The reason is that the brain has a sheath of connective tissue cells, the astrocytes, surrounding it, forming a barrier to passive diffusion for polar drugs. In addition, the endothelial cells of the brain capillaries are joined more tightly together, curtailing further the diffusion of polar drugs to the brain. Lipid soluble drugs can diffuse into the brain more readily and bring forth their effects Placental barrier - this consists of several layers of cells between the maternal and fetal circulatory systems. Diffusion of polar drugs is limited: However, lipid-soluble drugs can pass through the barrier. Fetuses are rich in lipids and may form a reservoir for sequestering lipid soluble drugs Phase 1 - these biochemical metabolism reactions include oxidation, reduction and hydrolysis, which transforms the drugs into metabolites. A family of enzymes called cytochrome P-450 is responsible for these reactions. Phase II - these biochemical metabolism reactions involve the addition or conjugation of subgroups, such as -OH, -NH and -SH to the drug molecules. These reactions give rise to more polar molecules, which are less lipid-soluble and are excreted from the body Expression of Clearance of a Drug - CL = Rate of drug elimination/Drug concentration in the blood Single dose - This type of toxicity testing is conducted for several purposed, including the determination of repeated doses, identification of organ is subjected to toxicity, and provision of data for starting doses in human clinical trials. Various characteristic of the animals are monitored, including weights, clinical signs, organ functions, biochemical parameters, and mortality. At the completion of the study, animals are killed and autopsies are preformed to analyze the organs, especially the targeted organ for the drug Repeated Dose - In this type of toxicity study the aim is to evaluate the longer-term effects of the drug in animals. Plasma drug concentrations are measured and pharmacokinetics analyses are performed. Vital functions studied include cardiovascular, respiratory and nervous systems. Animals are retained at the end of the study to check toxicity recovery Carcinogenicity - type of study that is carried out to identify the tumor-causing potential of a drug. Reproductive toxicology - The aim of these studies is to assess the effect of the potential drug on mammalian reproduction MRSD - maximum recommended starting dose NOAEL - no observed adverse effect level HED - human equivalent dose Drug sample - is a unit of drug which is not intended to be sold and is intended to promote the sale of the drug product Sampling - may be the single most important factor in a pharmaceutical rep's success Section 503 of the Federal Food, Drug and Cosmetic Act - this prohibits the sale, purchase, offer to sell, purchase, or trade prescription drug samples and drug coupons. 3 Methods of E-Sampling - 1. physicians can order samples online, and samples are delivered by mail to each physician's practice 2. Physicians can go online, print out sample vouchers or coupons, and then give them to patients along with a prescription for the product indicated on the voucher or coupon. The patient then presents both the prescription and the voucher or coupon to the pharmacy to receive a smple or a discount on the prescription, respectively 3. Patients can go online and print their own sample voucher or coupon, ask their physician for a prescription for the product indicated on the voucher or coupon, and fill it at the pharmacy. This option is not available in most countries, where direct-to consumer advertising of pharmaceuticals is often prohibited by law. tips for incorporating e-sampling - - Educate your physician customers on e-sampling - Continue to unpack and put away samples - Work with Retail pharmacists - Helping to 'make do' Genotoxicity - These studies are to determine if the drug compound can induce mutations to genes 4 basic transport mechanisms - o Passive Diffusion o Facilitated Diffusion o Active transport o Pinocytosis Factors the distribution pattern depends on - distribution pattern depends on a number of factors: o Vascular nature of the tissue o Binding of the drug to protein molecules in blood plasma o Diffusion of the drug Routes of Excretion - o Kidneys o Lungs o Intestine and colon o skin Pharmaceuticals - Medicines and vaccines for human and animal use; products may have a trademark (brand) name or be generic, and they may be prescription or over-the counter Diagnostic - Equipment and supplies used in screening, detecting, and monitoring disease, can range from simple home testing kits to sophisticated diagnostic imaging technologies Medical Devices - Advanced instrumentation and appliances used for medical therapy, such as joint replacements, implantable defibrillators, and pacemakers; also, drug delivery devices such as syringes, infusion pumps, metered-dose inhalers, and transdermal patches Medical Supplies - Commodity, high-volume supplies used such as surgical gowns and gloves Durable Medical Equipment - Reusable products for health-related use in the home, such as walkers, wheelchairs, oxygen equipment, prosthetics and hospital beds Medical Library - One of the oldest methods of acquiring medical information, most hospitals or clinics will have a library where current information will be available Medical Journals - These are considered good sources of information. They provide current perspectives from leading experts on various disease states and treatment options. Major and current studies will be published in the more reputable ones Specialists - They are usually involved in medical research. You will most often find them at universities or medical schools but they may also be found in private practice. They perform the testing and do the necessary research for new products. Approvable letter - Letter's sent by the FDA to the applicant indicating whether the application (NDA) or abbreviated application (ANDA) for a product substantially meets the necessary requirements and whether or not the agency believes that it can approve the application or abbreviated application if specific additional information or material is submitted or specific conditions (for example, certain changes in labeling) are agreed to by the applicant Fast- Track Drugs - Approval is provided for drugs that meet medical needs for patients with serious or life-threatening conditions. Placebo - is an inactive pill, liquid or powder that has no treatment value. In clinical trials, experimental treatments are often compared with this to assess the treatments effectiveness Placebo Effect - The effect produced by a placebo due to the expectations of the patient. The effect in placebo-controlled clinical trials is generally measured by comparison of the effect observed in patients receiving the placebo treatment with the effect observed in patients receiving the active treatment Control or Control Group - This is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while this group is given either a standard treatment for the illness or a placebo. Blinded of Masked Study - This study is one in which participants do not know whether they are in the experimental or control group in a research study. Those in the experimental group get the medications or treatments being tested, while those in the control group get a standard treatment or no treatment Double-Blind or Double Masked Study - This study is one in which neither the participants nor the study staff know which participants are receiving the experimental treatment and which ones are getting either a standard treatment or a placebo. These studies are performed so that neither patient nor doctor expectations about the experimental drug can influence the outcome Asymptomatic - without signs or symptoms of disease Edema - Swelling Indication - In terms of drug approval, the exact cause or purpose for whether a drug is approved by the FDA to be prescribed Institutional Review Board - A committee of physicians, statisticians, community advocates, and others, which ensures that a clinical trial is ethical and that the rights of the study participants are protected. All clinical trials in the U.S. must be approved by this committee before they begin Study Protocol - The general design and operating features of a trial. It is distinguished from the study manual of operations by its generality and absence of specific details needed for day-to-day execution of the trial. Toxicity - The extent, quality, or degree to which a substance is poisonous or harmful to the body Treatment Group - A group of patients assigned to receive a specified treatment Off Label - Usage of a medication for purposes other than the specific ones appearing in the labeling Off Label - Usage of a medication for purposes other than the specific ones appearing in the labeling Anatomy - the study of the basic structure of the body Physiology - the study of how those body structures function Clinical Pharmacology - the study of the effects and movement of drugs I the human body Drug - defined by the United States law as any substance (other than a food) or device intended for us in the diagnosis, cure, relief, treatment, or prevention of disease intended to affect the structure or function of the body Drug Abuse - the excessive and persistent use of mind-altering substances without medical need Preclinical testing - testing that gathers information about how the drug works, how effectively it works, and what toxic effects it produces, including possible effects on reproductive capacity and the health of offspring. Margin of safety - The difference between the usual effective dose and the dose that induces severe or life-threatening side effects Drug Administration - the giving of a drug by one of several means (routes) Drug Kinetics (pharmacokinetics) - involves what the body does to a drug, including the processes of absorption, distribution, metabolism, and elimination, and how long these processes take Drug treatment - requires getting a drug to its target site or sites - specific sites in tissue where the drug performs its actions Oral Route - when a drug is taken by mouth Subcutaneous route - route where a needle is passed into fatty tissue just beneath the skin. The drug is injected, then moves into small blood vessels (capillaries) and is carried away by the bloodstream or reaches the bloodstream through the lymphatic vessels This route is used for many protein drugs because such drugs would be digested in the digestive tract if they were taken orally. Intravenous route - route where a needle is inserted directly into a vein Infusion - the solution is moved by gravity (from a collapsible plastic bag) or by an infusion pump through thin flexible tubing to a tube (catheter) inserted in a vein, usually in the forearm Intrathecal route - route where a needle is inserted between two vertebrae in the lower spine and into the space around the spinal cord Sublingual Route - route where drugs are places under the tongue so that they can be absorbed directly into the small blood vessels that lie beneath the tongue. Rectal Route - route where a drug is administered rectally as a suppository Vaginal Route - route where drug is administered vaginally to women as a solution, tablet, cream, gel, or suppository Ocular Route - route where a drug can be mixed with inactive substances to make a liquid, gel, or ointment, so that they can be applied to the eye Nasal Route - route where a drug is to be breathed through the thin mucous membrane that lines the nasal passages, it must be transformed into tiny droplets in air (atomized) Cutaneous Route - route where drugs applied to the skin are usually used for their local effects and thus are most commonly used to treat superficial skin disorders. Depending on the consistency of the inactive substances, the formulation may be an ointment, a cream, a lotion, a solution, a powder, or a gel. Transdermal Route - route where drugs are delivered body wide though a patch on the skin Wasting the medication - disposal of controlled medications by flushing it into the sewer line. For controlled substances, you must ask someone to witness and document the disposal Medication error - the inappropriate or incorrect administration of a drug that should be preventable though effective system controls involving physicians, pharmacists, nurses, risk-management personnel, legal counsel, administrators, and patients Drug absorption - is the movement of a drug into the bloodstream Modified release - drug products that are specially formulated to release their active ingredients slowly or in repeated small amounts over time usually for a period of 12 hours or more. Also known as: controlled-release, sustained release, or extended release Drug distribution - the movement of drug to and from the blood and various tissues of the body (for example: fat, muscle, and brain tissue) and the relative proportions of drug in the tissues Drug metabolism - the chemical alteration of a drug by the body Pro-drugs - drugs that are administered in an inactive form, which is metabolized into an active form; the resulting metabolites produce the desired therapeutic effects Drug elimination - the removal of drugs from the body Drug Dynamics (pharmacodynamics) - involves what a drug does to the body. It describes the therapeutic effects of drugs (such as relief of pain and reduction of blood pressure) and their side effects. Also describes where (the site) and how (the mechanism) a drug acts on the body Pharmaceutics - the science of formulating drugs into different types of preparations such as tablets, ointment, injectable solutions, or eye drops. It also studies the ways in which various drug forms influence pharmacokinetic and pharmacodynamics activities of the active drug. Pills - a single-dose unit of medicine made by mixing the powdered drug with a liquid such as syrup and rolling it into a round or oval shape Tablet - a pharmaceutical preparation made by compressing the powdered form of a drug and bulk-filling material under high pressure. Capsule - a medication dosage form in which the drug is contained in an external shell Sustained Release - drug forms contain several doses of a drug. The doses have special coatings that dissolve at different rates; therefore, the drug is released into the digestive system gradually. Enteric coating - coating on some tablets and capsules that keeps them from dissolving in the stomach, which contains hydrochloric acid. These drugs don't dissolve until they reach the intestine. Caplet - is shaped like a capsule but has the form of a tablet. The shape and film coating make swallowing easier Gel Cap - an oil-based medication that is enclosed in a soft gelatin capsule Powders - a drug that is dried and ground into fine particles. Granules - a small pill, usually accompanied by many others encased within a gelatin capsule Troches or Lozenges - a hard or semisolid dosage form containing a medication intended for local application in the mouth or throat. Liquid Drugs - liquid preparations include drugs that have been dissolved or suspended Syrups - aqueous solutions containing high concentration of sugars, syrups, and linctuses which may or may not have medicinal substances added Solutions - a drug or drugs dissolved in an appropriate solvent. Ex. Elixirs, fluid extracts, spirits, and tinctures Elixirs - a drug vehicle that consists of water, alcohol and sugar Fluid Extracts - a concentrated solution of a drug removed from a plant source by mixing ground parts of the plant with a suitable solvent, usually alcohol, and then separating the plant residue from the solvents Mixtures and Suspensions - an agent is mixed with a liquid but not dissolved. These preparations must be shaken before being taken or administered to the patient Tinctures - an alcoholic preparation of a soluble drug, usually from a plant source. Emulsions - a pharmaceutical preparation in which two agents that cannot ordinarily be combined or mixed Spirits or Essences - an alcohol-containing liquid that may be used pharmaceutically as a solvent Liniments - liquid suspensions for external application to the skin to relieve pain and swelling Gels or Jellies - a jellylike, semisolid substance in a non fatty base that may be used for topical application and contains fine particles. Lotions - suspensions of drugs in a water base for external use. Aerosols - generally classified as liquid drugs because they often contain a mist. They are delivered by oral inhalers or nebulizers that allow for rapid absorption into the blood circulation. Magmas - contain particles suspended in a liquid, and exhibit a more pasty quality in their consistency than other suspensions Topical Drugs - drugs that are applied to the skin Receptor - a molecule with a specific three-dimensional structure, which allows only substances that fit precisely to attach to it Agonists/antagonists - classification for drugs that target receptors Inhibitors/activators (inducers) - classification for drugs that target enzymes Pharmacogenetics - the study of genetic differences in the response to drugs Drug-drug Interactions - changes in a drug's effects caused by another drug taken during the same time period Dietary supplement-drug interaction - changes in a drug's effects caused by a dietary supplement taken during the same time period Drug-Food Interactions - changes in a drug's effects caused by food (including beverages) consumed during the same time period. Tolerance - a person's diminished response to a drug, which occurs when the drug is used repeatedly and the body adapts to the continued presence of the drug. Resistance - the ability of microorganisms or "cancel" cells to withstand the effects of a drug usually effective against them Overdose Toxicity - refers to serious, often harmful, and sometimes fatal toxic reactions to an accidental overdose of a drug (because of a doctor's, pharmacist's, or patient's error) or to an intentional overdose (homicide or suicide). Compliance - the degree to which a person take prescribed drugs as directed Mechanism of Action - the way in which an API works in the body The Active Pharmaceutical Ingredient (API) - the ingredient in drugs that is intended to produce the desired change in the body Pharmacodynamics - assesses the biochemical effects of the drug on the body at various doses, or more specifically, the drug's actions and effects at a molecular level Cell Membrane - all cells are wrapped in a semi-permeable membrane that protects them from outside elements and distinguished them from their surroundings. Also is a barrier that selectively facilitates or blocks entry and exit of various substances into and out of the cell such as drugs, nutrients, and waste. Water usually flows freely Nucleus - the brain of the cell that regulates all activities. Some cells do not have one Cytoplasm/Protoplasm - the substance inside the outer membrane and outside of the nucleus. This contains most of the intracellular fluid Extracellular Fluid - body fluid located between or outside cells. Consists of interstitial fluid or fluid between cells and intravascular fluid or fluid within the blood such as plasma Tissues - a group of similarly specialized cells that perform the same function. Organs - specialized cells and tissues grouped together to perform a specific body function for a common purpose (kidney, heart, intestines, skin, etc.) Plasma - the liquid portion of the blood that caries proteins and other substances Proteins - made up of chains of amino acids, some of which are known as essential amino acids because the body does not manufacture them but must receive them from outside the body with food Fats - stored in special body tissues as great sources of reserve energy. Necessary for growth and other body function such as absorption of some vitamins Carbohydrates - the body's immediate source of energy. It is broken down into glucose and used for immediate metabolic reactions Vitamins - substances necessary for growth, development and normal regulation of metabolic processes must be taken from outside the body. Minerals - substances necessary for body processes such as the balance of body fluids, the formation and maintenance of bones, teeth, and the proper functioning of muscles. The main ones are: calcium, potassium, iron, sodium, phosphorous and iodine The Cardiovascular System - consists of the heart, the blood vessels, and the blood itself. The cardiovascular system is the body's main transportation system. It provides nutrients and hormones as well as removes waste from the cells Respiratory System - consists of the nasal passages, the tracheas, the diaphragm and the lungs. It performs the exchange of oxygen and carbon dioxide between the body and the environment Gastrointestinal System - consists of the mouth, esophagus, stomach, liver, pancreas, gallbladder, and small and large intestines. Use by the body to acquire the energy and nutrients it needs to sustain itself Nervous System - consists of the central nervous system (brain, spinal cord, nerves, etc.) and the peripheral nervous system such as the senses. This system conducts electrical signals throughout the body and allows it to interact properly with its environment Musculoskeletal System - Consists mostly of the muscles, the bones and other minor systems. This system is primarily responsible for the body's basic frame support and movement as well as its ability to perform physical work Reproductive System - consists of the penis, testes, and seminal fluids (male) and the ovaries, oviducts, uterus, vagina and mammary glands (female). The system's major role is to manufacture, transmit and maintain the cells and environment necessary for reproduction Immune system - consists of the lymph nodes, vessels, and cells; its major purpose is to maintain the integrity of the body by attacking and removing invading foreign substances and microbes. It also helps remove excess fluids from the body Homeostasis - a state of constant, consistent and balanced internal environment in the body. The body's normal resistance to change that drives the body toward maintaining its internal equilibrium. When faced with danger or pleasure, the body secretes hormones and makes other adjustments necessary to maintain the normal functioning of vital organs, as well as the levels of electrolytes, nutrients and fluids it needs to survive Drug Distribution and Elimination - drug delivery systems, route of administration, and modes of excretion Pharmacodynamics - study of the biochemical and physiological effects of drugs and their mechanisms of action Pharmacokinetics - study of how a drug is processed by the body, with emphasis on the time required for absorption, duration of action, distribution in the body and method of excretion Oral Administration or p.o. - usually refers to tablets, capsules, liquids taken by mouth Intravenous or IV - usually refers to drugs injected directly into the veins Intradermal - refers to drugs given by injection under the skin Transdermal - refers to drugs taken through the skin into the systematic circulation, such as through a patch Sublingual - refers to drugs taken under the tongue and absorbed directly and almost immediately into the blood-stream through the mucous membranes of the mouth Intramuscular - refers to drugs given by direct injection into muscle tissue such as the buttocks, the upper arm or thighs Inhalation - refers to drugs taken through the lungs by inhaling in aerosol form Topical - drugs administered through the skin for local effects on that area of the skin Rectal or Intravaginal - drugs delivered through the rectum in suppository form or vaginal cream Absorption - the process by which a drug disintegrated in the stomach as molecules travel across the epithelial cell membranes lining the stomach and intestines, then reach the filtering system in the liver called the Portal System before reaching the systemic circulation. When a drug is taken by mouth, it is metabolized in the liver and converted from the parent drug into metabolites for therapeutic activity or excretion before it reaches the systemic circulation. The amount of drug reaching the systemic circulation is reduced by what is known as the first pass effect, that is, some of the drug is metabolized by certain enzymes in the liver and stomach, excreted, and never reaches the systemic circulation. HT presence of food in the stomach, acidity level, the structure and binding of the tablet or capsule and many other situations can influence this Bioavailability - this is the rate and extent to which the active or therapeutic ingredient is absorbed from a drug product and becomes available at the intended site of drug action. Once the drug reaches the systemic circulation, it is transported by the blood to every cell and to the rest of the areas where blood is circulated. This is measured by the amount of drug in the plasma. Peak plasma concentration is achieved when the drug absorption rate equals the excretion rate Bioequivalence - two pharmaceutically equivalent drug products are this if after drug administration; they provide similar effects with respect to efficacy and safety. Drugs can be therapeutically equivalent even if they differ in shape, size, color, packaging, etc. A statistical variability of +/-20% is allowed. Actual variability is in the range of 3.5-4%. Mechanism of Action - the process by which a given drug works in the body to achieve its intended therapeutic effect Minimum effective Dose - the lowest dose of a drug that can be given to a patient to produce any therapeutic effect Maximum Effective Dose - the highest dose beyond which more of a given drug will produce no additional therapeutic effect Duration of Action - the time interval within which a given dose of a drug is expected to have therapeutic effect Half-Life of a Drug - the period of time it takes for a specific amount (concentration) of drug in the body to be reduced, through the excretion or elimination process, to exactly one-half of that original amount AUC (Area under the Curve) - when blood concentration is used to measure bioavailability, this represents the extent of drug absorption or the quantity of drug that appears in the bloodstream following oral administration Cmax - peak plasma concentration on a measuring curve Tmax - time of peak plasma concentration on a measuring curve Titration - the process of adjusting drug doses to achieve the maximum positive therapeutic effects while minimizing adverse or side effects First Pass Effect - The metabolizing process in the liver that suppresses the amount of drug that eventually reaches the systemic circulation and the site of action Onset of Action - the time it takes for a drug to start having any intended effect after it is administered Steady State - when a given dose of drug is being taken at regular intervals, absorption and elimination (and therefore drug plasma concentration) become fairly constant. CNS - Central Nervous System CSF - Cerebrospinal Fluid Lipid Soluble - ability to dissolve in lipids or fat tissue Blood Brain Barrier - a protective layer of cells surrounding the blood vessels that feed blood to the brain. It is through that lipid soluble drugs are better able to permeate this barrier and therefore produce more CNS activity. QD - once a day BID - twice a day TID - three time a day QID - four times a day PRN - as needed STAT - immediately Sustained Release - drug delivery formulations designed to delay the absorption process so that a drug can be given in fewer daily dosages and improve patient convenience or to minimize inconsistencies in blood concentration levels thereby avoiding adverse effects caused by those peaks Drug-Dug Interaction - the physiologically significant effects produced by the interaction of two drugs in the body. Not all drugs are affected by the presence of other drugs. can be positive as well as negative Drug-Food Interaction - The physiological effects produced by the interaction of food and a given drug Side Effects - the actions or effects of a drug beyond what it is clinically intended to do.Can be expected or unexpected, desired or undesired even though the general public usually refer to it as undesired or negative effects, such as headache, skin irritation, bloating or liver damage Adverse reactions - all undesirable effects of a medication. All drugs may cause such reactions, so that periodic monitoring is necessary to detect any that do occur, even though their occurrence may be uncommon Elimination - The process by which a drug or its metabolites are removed from the body. Most of it is done by the urine through its filtration of water-soluble substances. Damaged kidneys are not able to filter drugs and other substances properly, which can lead to accumulation, toxicity and further damage. Therefore, dosage adjustments may be necessary for such patients. Some also occurs through perspiration and other body waste elimination processes Injection Routes - Administration by injection (parenteral administration) includes the subcutaneous, intramuscular, intravenous, and intrathecal routes. Epithelial tissues - tissues that cover the surface of the body and form the lining of body cavities, organs, and blood vessels; connective tissues, such as tendons and ligaments, connect and support other tissues, organs, and other body parts. Muscle tissues - Type of tissue that allow for contraction as needed by the body for movement Nerve tissues - Type of tissues that generate, carry or conduct electrical impulses in and out of the brain, nerves and spinal cord Protein Binding - the ability of certain drugs to bind to plasma protein. This is important in determining amount of available drug at the site of action, toxicity and other relevant physiological effects Authorized Distributor - Any distributor of a prescription drug that has a written agreement with the manufacturers of the prescription drug and conducts at least two transactions with the manufacturer of the prescription drug within any 24-month Average Wholesale Price (AWP) - a published wholesale price or "list price" suggested by the manufacturer of the drug. Although it does not capture the actual transaction prices, it serves as a reference for pricing, negotiations, and reimbursements Brokerage - the combination of drop-ship and dock-to-dock delivery services provided by wholesalers. In these services, wholesalers do not bring the product into their warehouses. Buy-Side Margin - The term refers to the early payment discounts and other earned or negotiated rebates and discounts received by the wholesalers from drug manufacturers. Further increases in the value of the wholesalers' inventories as manufacturers' prices rise are considered this Chain Drug Store - A company that owns and operates four or more pharmacies. Food store and mass merchandiser pharmacies are also considered this. Ex. Walgreen's, CVS, OSCO Dock-To-Dock Delivery - where a wholesaler obtains the drugs from the manufacturer and delivers them to a dispenser's own warehouse without taking the drugs into its own inventory. Also referred as non-stock sales Drop Shipment - where a drug manufacturer directly delivers the drug to a dispenser, but the order and payments are made through a wholesaler Float - the time differential between when a wholesaler receives payment from its customer (i.e. retail dispenser, health care organization, etc.) and when the payment is due to its supplier (i.e. pharmaceutical manufacturer or other wholesaler) Group Purchasing Organization (GPO) - An entity consisting of two or more hospitals or other health care entities that is formed to offer its members access to purchasing contracts for health supplies (i.e. pharmaceuticals, biologics, medical/surgical equipment, laboratory supplies, and other capital equipment). This entity actively negotiate contracts with manufacturers on behalf of their members, provide their members access to the purchasing contracts of other similar entities, and/or have central purchasing supply sites which are utilized by their members In-State Wholesaler - a wholesaler that distributes drug products in a given state and is physically located in that state Independent Drug Store - a company that owns and operates three or fewer pharmacies. Also known as community or neighborhood pharmacies Integrated Delivery Network (IDN) - Also known as integrated healthcare delivery network (IHDN), integrated delivery system (IDS), or integrated health. Healthcare system (IHS). A financial and management structure that unites hospitals, physicians, ambulatory care sites, and managed care plans through ownership or exclusive formal agreements to provide a system to deliver a continuum of healthcare services. The IHDN appears totally integrated to the patient, provider, and payer throughout the healthcare system. Increasingly, a shared financial information system and optimization of resources connect the structural components of the IHDN Mail-Order Pharmacy - A pharmacy that dispenses prescription to patients who submit their prescriptions by mail or fax. The pharmacy then mails the filled prescription to the patient. This type of pharmacies generally serve patients on long-term drug therapies and those without immediate drug needs. The average size of prescriptions (i.e. the number of capsules or tablets) dispensed by mail-order pharmacies is usually 3 times larger than those dispensed by retail pharmacies Manufacturer-Direct Sale - the type of sale that bypasses the need for any intermediary distributor. The product is sold and shipped directly by the manufacture to the dispenser. Mass Merchandisers - an establishment, also known as a department store, that is primarily engaged in retailing a wide range of merchandise, including apparel, furniture, appliances, hardware, food, cosmetics, and prescription drugs. Prescription drugs are dispensed through on-site pharmacy. Examples: Wal-Mart, Target, and Costco Non-Stock Sales - Brokerage sales, dock-to-dock delivery sales, drop shipments, and any other forms of sales not placed in inventory. These generally have a significantly lower margin than stock sales Out-of-state Wholesaler - a wholesaler the distributes drug products in a given state but is physically located in another state Pharmacy Benefit Management Company (PBM) - An entity that administers the prescription drug part of health insurance plans on behalf of plan sponsors, such s self- insured employers, insurance companies, and health maintenance organizations (HMO's). These provide pharmacy claims processing and mail-order pharmacy services in addition to other services, such as rebate negotiations with pharmaceutical manufacturers, development of pharmacy networks, formulary management, drug utilization reviews, generic drug substitution, and disease management programs. Rebate - the amount that the manufacturer of the drug pays to an insurer or health plan for each unit of drug dispensed. These arrangements exist between drug manufacturers and Medicaid agencies, HMO's, and other insurers or drug plans, and generally bypass the pharmacy. Also referred to as "after market" arrangements because they do not affect the prices paid at the time of service Self-Warehousing - a type of distribution system where the retail of the institutional dispenser takes on the task of distribution itself. Instead of relying on an outside distributor, the retailer or the institutional dispenser buy direct from the manufacturer, stores the drugs in one or more of its own warehouses, and then delivers them to its pharmacy or hospitals as needed. Most prominent among the chain drug stores Sell-Side Margin - wholesaler revenues that are generated from fees and other charges obtained from dispensers. During the 1980 to 2000 period, this has declined from 5.5% to .35% Up Charge - the percentage fee that is paid by the dispenser to the wholesaler for the cost of distribution Primary purpose of Package Insert - its purpose is to provide practitioners with essential information they need to prescribe the drug safely and effectively for the care of patients Sections required in a package insert - 1. Description 2. clinical pharmacology 3. indications and usage 4. contradictions 5. Warning/Precautions 6. Adverse Reactions 7. Drug Abuse and Dependence 8. Overdosage 9. Dosage and Administration 10. How Supplied mnemonic: Dogs Call Iguanas Cowards While Alligators Dance On Drenched Hardwood Description of Package Insert - This section must include: - the proprietary name and the established name - qualitative and/or quantitative ingredient information Clinical Pharmacology of Package Insert - under this section, the labeling must contain information relating to the human clinical pharmacology and action of the drug in human. Must include following subheadings and info: o Mechanism of action o Pharmacodynamics. Biochemical or physiological pharmacological effects of the drug or active metabolites o Pharmacokinetics. Cmax, AUC, half-life, etc. Indications and Usage of Package Insert - This section must state: o the drug is indicated for the treatment, prevention, mitigation, cure or diagnosis, cure or diagnosis of a recognized disease or condition o the drug is indicated for the treatment, prevention, mitigation, cure or diagnosis of an important manifestation of a recognized disease or condition o the drug is indicated for the relief of symptoms associated with a recognized disease or syndrome o the drug, if used for a particular indication only in conjunction with a primary mode of therapy (e.g. diet, surgery, behavior changes, or some other drug), is an adjunct to the mode of therapy - this section must also state the recommended usual dosage, the usual dosage range, and if appropriate, an upper limit beyond which safety and effectiveness has not been established. - Dosages must be stated for each indication and sub-population when appropriate Contradictions of Package Insert - this section must describe situations in which the drug should not be used because the risk of use clearly outweighs any possible therapeutic benefit Warning/Precautions of Package Insert - the labeling in this section must describe clinically significant adverse reactions and other potential safety hazards, including those resulting from drug-drug interactions; limitations in use imposed by them; and steps that should be taken if they occur Adverse Reactions of Package Insert - This section describe serious adverse reactions and potential safety hazards, limitations in use imposed by them, and steps that should be taken if they occur Drug Abuse and Dependence of Package Insert - - Controlled Substance: if the drug is controlled by the Drug Enforcement Administration, the schedule in which it is controlled must be stated - Abuse: must state the types of abuse that can occur with the drug and the adverse reactions pertinent to them. Particularly susceptible patient populations must be identified - Dependence: must describe characteristic effects resulting from both psychological and physical dependence that occur with the drug and must identify the quantity of the drug over a period of time that may lead to tolerance or dependence, both Overdosage of Package Insert - This section must describe the signs, symptoms, and laboratory findings of acute overdoses and the general principles of treatments Dosage and Administration of Package Insert - This section would include the most common dosage regimen(s) and critical differences among population subsets, monitoring requirements, and other therapeutically important clinical pharmacological information How Supplied of Package Insert - This section should be a concise summary of information concerning the product's dosage form(s) Patent - is a form of personal property that provides the owner with the right to exclude others from making, using, selling, offering for sale, or importing into the United States the inventions described How long is a patent granted for? - Patents expire 20 years from the date of filing. Exclusivity - is exclusive marketing rights granted by the FDA upon approval of a drug and can run concurrently with a patent or not Generic drug - is a drug that is identical, or bioequivalent to the originator brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Generic name - name of a drug that is the chemical or scientific name, which describes the active drug ingredients Orange Book - is a list of "Approved Drug Products with Therapeutic Equivalence". Single Source Drug Products - There is only one approved product available for that active ingredient and dosage form Multi Source Drug Products - Pharmaceutically equivalent products available from more than one manufacturer Chemical Equivalents - Multi source products which contain essentially identical amounts of identical active ingredients in identical dosage forms and which meet existing physical chemical standards Biological Equivalents - Chemical equivalents which when administered in the same amounts will provide the same biological or physiological availability as measured by blood and urine levels Therapeutic Equivalents - Chemical equivalents which when administered in the same amounts will provide the same therapeutic effect as measured by the control of a symptom or disease Generic Substitution - The act of dispensing a different brand (unbranded generic product) for the product described, i.e. chemically the exact same drug entity in the same dosage form but manufactured or distributed by different companies Pharmaceutical Alternatives - Drug Products that have the same therapeutic effect and strength but differ in the salt, ester, or dosage form and are administered by the same route Pharmaceutical Substitutions - The act of dispensing a pharmaceutical alternative for the product prescribed Therapeutic Alternatives - Drug products containing different therapeutic moieties but of the same pharmacological or therapeutic class that can be expected to have similar therapeutic effects when administered in therapeutically equivalent doses FDA's Criteria for Equivalence - The following criteria is required - the drugs are approved as both safe and effective - they are pharmaceutical equivalents i.e. o contain identical amounts of the same active ingredients in the same dosage form and route of administration o they meet applicable standards of strength, quality, purity and identity - They are bioequivalent o Meet acceptable in-vitro standards o If not, meet appropriate in-vivo bioequivalence standards - They are adequately labeled - They are manufactured in compliance with FDA's CGMP regulations Is there a significant quality difference between generic and brand drugs? - No because generic manufacturers must demonstrate to the FDA that a generic drug has the same medical effect as its brand name equivalent, by measuring the rate and extent of drug absorption - Generic drugs must also contain identical amounts of the same active drug ingredients, in the same dosage form and strength, as their brand name counterparts Generic Drug First-to-File Exclusivity - the first generic drug manufacturer to file an ANDA with the FDA on a new off patent drug receives a 6 month marketing exclusivity The Hatch-Waxman Act - also known as the Drug Price Competition and Patent Term Restoration Act of 1984, it is considered the most significant drug-related legislation affecting the pharmaceutical and healthcare industries since 1962. - It made it easier to bring generic drugs to the market by requiring the FDA to only look at bioavailability studies in order to approve an ANDA. - It gave protection to the research-based manufacturers by providing a 30-month automatic cooling off period once the innovator company decided to challenge an ANDA for patent infringement Generically Equivalent Drugs - Drug formulations of identical composition, with respect to the active ingredient (i.e. drugs that meet current official standards of identity, purity, and quality of active ingredient Orphan Drug (ODE) exclusivity - 7 years New Chemical Entity (NCE) Exclusivity - 5 years "other" Exclusivity - 3 years for a "change" if criteria are met Pediatric Exclusivity (PED) - 6 months added to existing Patent/Exclusivity Patent Challenge (PC) Exclusivity - 180 days (this exclusivity is for ANDA's only) Orange Book Rating A - Products for which there are no known or suspected bioequivalence problems Orange Book Rating AA - Products in conventional dosage forms with no bioequivalence problems Orange Book Rating AN - Solutions and Powders Orange Book Rating AO - Injectable Oil Solutions Orange Book Rating AP - Injectable Aqueous Solutions Orange Book Rating AT - Topical Products Orange Book Rating B - Drug products requiring further FDA investigation and review to determine equivalence Clinical Trial Experimental - study in which the exposure status (e.g. assigned to active drug versus placebo) is determined by the investigator Randomized Controlled Trial - a special type of clinical trial in which assignment to an exposure is determined purely by chance Cohort Study - Observational study in which subjects with an exposure of interest (e.g. hypertension) and subjects without the exposure are identified and then followed forward in time to determine outcomes (e.g. stroke) Case Control Study - observational study that first identifies a group of subjects with a certain disease and a control group without the disease, and then looks to back in time (e.g. chart review) to find exposure to risk factors for the disease. This study is well suited for rare diseases Cross Sectional Study - Observational study that is done to examine presence or absence of a disease or presence or absence of an exposure at a particular time. Since exposure and outcome are ascertained at the same time, it is often unclear if the exposure preceded the outcome Case report or Case Series - Descriptive study that reports on a single or a series of patients with a certain disease. This type of study usually generates a hypothesis but cannot test a hypothesis because it does not include an appropriate comparison group Bias - any systemic error in the design or conduct of a study that results in a mistaken estimate of an exposures effect on risk or disease Selection Bias - bias introduced by the way in which participants are chosen for a study. For example, in a case control study using different criteria to select cases (e.g. sick, hospitalized population) versus controls (young, healthy outpatients) other than the presence of disease can lead the investigator to a false conclusion about an exposure Confounding - This occurs when an investigator falsely concludes that a particular exposure is causally related to a disease without adjusting for other factors that are known risk factors for the disease and are associated with the exposure Mean - equals the sum of observations divided by the number of observations Median - equals the observation in the center when all observations are ordered from smallest to largest; when there is an even number of observations the median is defined as the average of the middle two values Mode - equals the most frequently occurring value among all observations Percentile - equals the percentage of a distribution that is below a specific value. Interquartile Range - refers to the upper and lower boundary defining the middle 50% of observations. The upper boundary is the 75th percentile and the lower boundary is the 25th percentile Spread - (or variability) describes the manner in which data are scattered around a specific value (such as the mean) The most common measures are range, standard deviation and standard error of the mean Range - is the difference between the largest observation and the smallest Standard Deviation - measures the spread of data around the mean. One of this includes 68% of the values in a sample population and two include 95% of the values Standard Error of the Mean - describes the amount of variability in the measurement of the population mean from several different samples. This is in contrast to the standard deviation, which measures the variability of individual observations in a sample Incidence - the number of new events (e.g. death or a particular disease) that occur during a specified period of time in a population at risk for developing the events Incidence Rate - A term related to incidence that reports the number of new events that occur over the sum of time individuals in the population were at risk for having the event Prevalence - the number of persons in the population affected by a disease at a specific time divided by the number of persons in the population at the time Measures of Association - the types of measures used to define the association between exposures and outcome depends upon the type of data Relative Risk (risk ratio) - defined as the ratio of the incidence of disease in the exposed group divided by the corresponding incidence of disease in the unexposed group Odds ratio - is defined as the odds of exposure in the group with disease divided by the odds of exposure in the control group. It is often used to approximate the relative risk in case-control studies attributable risk or risk difference - is a measure of absolute risk. It represents the excess risk of disease in those exposed taking into account the background rate of disease. IT is defined as the difference between the incidence rates in the exposed and non-exposed groups Population Attributable Risk - is used to describe the excess rate of disease in the total study population of exposed and non-exposed individuals that is attributable to the exposure. This measure is calculated by multiplying the Attributable Risk by the proportion of exposed individuals in the population. NNT - The number needed to treat - It is the reciprocal of the absolute risk reduction absolute risk reduction - the absolute adverse event rate for placebos minus the absolute adverse event rate for treated patients Validity - refers to the extent to which a test or surrogate is measuring what we think it is measuring Sensitivity - is defined as the ability of the test to identify correctly those who have the disease. It is the number of subjects with a positive test who have disease divided by all subjects who have the disease. Specificity - is defined as the ability of the test to identify correctly those who do not have the disease positive predictive value - is the probability of disease in a patient with a positive test. A positive likelihood ratio - ratio that tells us the odds of disease if the test result is positive. LR+ = Sensitivity/(1- Specificity Negative likelihood ratio - ratio that tells us the odds of disease if the test result is negative LR- = (1-Sensitivity) / Specificity confidence interval - gives a range of values within which there is a high probability (95% by convention) that the true population value can be found Type I error (alpha) - type of error in hypothesis testing that is the probability of incorrectly concluding there is a statistically significant difference in the population when none exists Type II error (beta) - type of error in hypothesis testing that is the probability of incorrectly concluding that there is no statistically significant difference in a population where one exists Power - is a measure of the ability to detect a true difference. Kaplan-Meier analysis - measures the ratio of surviving subjects (or those without an event) divided by the total number of subjects at risk for the event. Every time a subject has an event, the ratio is recalculated. These ratios are then used to generate a curve to graphically depict the probability of survival Cox proportional hazards analysis - is similar to the logistic regression method but with the added advantage that it accounts for time to a binary event in the outcome variable Abstract concept - the starting point for measurement, it is best understood as a general idea in linguistic form that helps us describe reality Association - this is a measurable change in one variable that occurs concurrently with changes in another variable. Positive association - this type of association is represented by change in the same direction. Negative association - this type of association is represented by concurrent changes in opposite directions Constant - it is an attribute of a concept that does not vary Construct validity - defines how well a test or experiment measures up to its claims. It refers to whether the operational definition of a variable actually reflect the true theoretical meaning of a concept Content validity - extent to which a test adequately represents the subject-matter content or behavior to be measured - commonly used in evaluating achievement or proficiency tests Continuous variable - this type of variable is a measure that can take on any value within a given interval or set of intervals: an innate number of positive values Dependent variable - the value of this variable depends on variations in another variable Discrete variable - this type of variable is a measure that is represented by a limited number of values Independent variable - this variable can be manipulated to affect variations or responses in another variable Interval data - these variables classify objects according to type and logical order but also require that differences between levels of a category are equal Nominal data - these are variable that classify objects according to type or characteristic Operationalize - this is the process of creating a measure of an abstract concept Ordinal data - these are variable that classify objects according to type or kind but also have some logical order Predictive validity - this is the ability of an indicator to correctly predict (or correlate with) an outcome Random variable - this type of variable is a measure where any particular value is based on chance by means of random sampling Ratio data - these variable have a zero starting point and classify objects according to type and logical order but also require that differences between levels of a category be equal Reliability - is the consistency or repeatability of your measurements (deals with quality of measurement Spurious association - this is an association between two variables that can be better explained by or depends greatly on a third variable Statistical control - this refers to holding the value of one variable constant in order to clarify associations among other variables. Statistical inference - this is the process whereby one reaches a conclusion about a population on the basis of information obtained from a sample drawn from that population. There are two such methods, statistical estimating and hypothetical testing Validity - extent to which a measurement is an accurate representation of the concepts Variable - a variable is a measure of a concept that can take on more than one value from one observation to the next Clinical Trial - "Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamics effects of an investigational product, and/or to identify any adverse reactions to an investigational product, and/or to study absorption, distribution, metabolism, and excretion of an investigational product with the object of ascertaining its safety and/or efficacy." Ethical requirements for clinical studies - o Social Value o Scientific Validity o Fair subject selection o Informed consent o Favorable risk-benefit ratio o Independent review o Respect for human subject Social Value - this ethical requirement is to ensure that the clinical trial is justified based on scientific research, and will result in improvements in health or advancement of scientific knowledge Scientific validity - ethical requirement that holds that: - the clinical trial should be conducted methodically with clear objectives and outcomes that are statistically verifiable. - The trial should not be biased, and should be able to be executed without unreasonable cavets and conditions Fair subject selection - Selection of subjects is based on scientific objects and not on whether the subject is privileged or vulnerable, or because of convenience. There must be documented evidence to support the choice of selection criteria. Informed consent - Ethical requirement where subjects are to be informed about the aims, methods, risks and benefits of the trial. The availability of alternatives should be explained to the subjects Phase I clinical trial - this phase of a clinical trial is the first experiment in which a drug is tested on the human body. The primary aim of the trial is to assess the safety of the new drug. The number of subjects is normally between 10 and 100 people. Depending on the complexity of the trial, the cost is around $10 million and the trial may last from several months to a year Phase II clinical trial - The aim of this phase of clinical trials is to examine the safety and effectiveness of the drug in the targeted disease group. A series of doses varying strengths may be used. The result of this trial is information needed to determine the effective dose and the dosing regimen of frequency and duration. the number of patients is normally in the vicinity of 50-500. The trial may take 1-2 years or more to complete, depending on the study of numbers and availability of patients.The cost for such a trial can be more than $20 million. Phase III clinical trial - The objective of this phase of a clinical trial is to confirm the efficacy of the drug in a large patient group. The trial is normally conducted in several hospitals in different demographic locations, to determine the influence of ethnic responses, together with incorporation of new criteria for fine-tuning the trial. This trial is also known as a multi-site. Because of the magnitude of the trial, the duration may be 3-5 years and the cost is around $50-$100 million Phase IV clinical trial - this phase of clinical trials are post-marketing approval trials to monitor the efficacy and side effects of the drug in an uncontrolled real-life situation. Also known as a post-market surveillance trial. Requirements for clinical trials in accordance to GCP - o Investigator o Investigator's brochure o Informed Consent o Protocol o Inclusion and exclusion and exclusion criteria o Case report form o Randomization, placebo-controlled and double-blinded o Monitoring o Adverse events o Statistics o Sponsor Investigator - is the person who conducts the trial. Whose responsibility is to ensure that GCP is being implemented in the course of the trial and the subjects' rights and welfare are respected Investigator's Brochure - is a collection of the information prepared and updated by the sponsor for the Investigator. The information consists of all the data relevant to the drug under investigation Protocol - This document sets out how a trial is to be conducted. It contains the rationale for the clinical trial, methodology on how the trial is designed, the number of subjects to be recruited, the markers or endpoints to show effectiveness of the drug, statistical methods to be used to analyze the data, how the subjects are protected in the trial, informed consent and confidentiality, as well as welfare and frequency of monitoring Inclusion and exclusion criteria - These criteria set out the conditions under which a person may or may not be included in the trial Case Report Form - All the information relating to a subject is recorded in this. They are part of the regulatory document, and the data are statistically analyzed and submitted to regulatory authorities for marketing approval of the drug Sponsor - This is the organization or individual that initiates the clinical trial and finances the study. The organization may be a government department, the pharmaceutical company, university or individual Clinical research organization - This is the organization that is contracted by the Sponsor to conduct and monitor the tria surrogate markers - Sometimes it is not possible to measure the direct effect of the drug. As a result this, otherwise known as endpoints are used to monitor the pharmacodynamics and pharmacokinetics of the drug. They may be changes in blood pressure, cholesterol level, concentration of certain enzymes, proteins, blood glucose levels and similar factors Clinical Statistics - In this, the effect of clinical variables on the diagnosing and treatment of diseases in humans is researched. Epidemiology - the influence of different factors on disease and health among individuals and populations is researched Bioinformatics - is a broad area of research which is basically concerned with the analysis of biological data on a molecular level Types of errors in hypothesis testing - - Type I error (alpha) - Type II error (beta Face validity - type of validity that evaluated whether the indicator appears to measure the abstract concept A.A. - Referring to medication dosage, means "of each" A.C. - Referring to medication dosage, means "before meals" AAHP (American Association of Health Plans) - the primary U.S. association of health plans, which includes health maintenance organizations (HMOs), preferred provider organizations (PPOs), other forms of managed care, and utilization review organizations (UROs) Absorption - The process in which a medication is absorbed into the bloodstream Absorption Rate - The rate at which a drug is taken into a person's blood stream within a specified time period. These rates can very from person to person, creating the challenge of refining a drug so that it is effective on people with slow rates but not toxic to people with fast rates Accelerated Approval - A specialized FDA mechanism implemented in the early 1990