PHARMACOLOGY - the science of drug action on biological system In general terms, pharmacology is the science of drug action on biological

systems. In its entirety, it embraces knowledge of the sources, chemical properties, biological effects and therapeutic uses of drugs. It is a science that is basic not only to medicine, but also to pharmacy, nursing, dentistry and veterinary medicine. Pharmacological studies range from those that determine the effects of chemical agents upon subcellular mechanisms, to those that deal with the potential hazards of pesticides and herbicides, to those that focus on the treatment and prevention of major diseases by drug therapy. Pharmacologists are also involved in molecular modeling of drugs, and the use of drugs as tools to dissect aspects of cell function. Integrating a depth of knowledge in many related scientific disciplines, pharmacologists offer a unique perspective to solving drug-, hormone-, and chemical-related problems which impinge on human health. As they unlock the mysteries of drug actions, discover new therapies, and develop new medicinal products, they inevitably touch upon all our lives. While remarkable progress has been made in developing new drugs and in understanding how they act, the challenges that remain are endless. New discoveries regarding fundamental life processes always raise new and intriguing questions that stimulate further research and evoke the need for fresh insight. A brochure, entitled Explore Pharmacology, is available upon request from the ASPET office that provides you with a broad overview of the discipline of pharmacology. It describes the many employment opportunities that await graduate pharmacologists, and outlines the academic path that they are advised to follow. If you feel a sense of excitement and enthusiasm about understanding drug action, and how drugs may be used to probe the physiological and biochemical processes of life, you should explore pharmacology. This is the first step into an absorbing, challenging and rewarding career. You may also read this brochure in Spanish online. A video, Research, the Ultimate Adventure, features interviews with Nobel Laureates, Gertrude Elion, George Hitchings and Julius Axelrod, talking to students about what got them interested in pharmacology. PHARMACOLOGY: Its scope and subdivisions Often confused with pharmacology, pharmacy is a separate discipline in the health sciences. It is the profession responsible for the preparation, dispensing, and appropriate use of medication, and provides services to achieve optimal therapeutic outcomes. If you are interested in pharmacy, see this link.

Pharmacology is the study of the effects of chemical agents of therapeutic value or with the potential toxicity on biological systems. It includes two closely associated areas: pharmacodynamics and pharmacokinetics. Pharmacodynamics is the study of the molecular, biochemical, and physiological effects of drugs on cellular systems and their mechanisms of action. Pharmacokinetics deals with the absorption, distribution, and excretion of drugs. Pharmacodynamic and pharmacokinetic aspects of action of chemical agents also apply to related areas of study, including toxicology and therapeutics. The Pharmacological Sciences can be further subdivided:

Behavioral pharmacology studies the effects of drugs on behavior. Research includes topics such as the effects of psychoactive drugs on the phenomena of learning, memory, wakefulness, sleep, and drug addiction, and the

behavioral consequences of experimental intervention in enzyme activity and brain neurotransmitter levels and metabolism. For more information about Behaviorla Pharmacology see the ASPET Division for Behavioral Pharmacology Web pages. Cardiovascular pharmacology concerns the effects of drugs on the heart, the vascular system, and those parts of the nervous and endocrine systems that participate in regulating cardiovascular function. Researchers observe the effects of drugs on arterial pressure, blood flow in specific vascular beds, release of physiological mediators, and on neural activity arising from central nervous system structures. For more information about Cardiovascular Pharmacology see the ASPET Division for Cardiovascular Pharmacology Web pages. Biochemical and Cellular pharmacology uses the methods of biochemistry, cell biology, and cell physiology to determine how drugs interact with, and influence, the chemical "machinery" of the organism. The biochemical pharmacologist uses drugs as probes to discover new information about biosynthetic pathways and their kinetics, and investigates how drugs can correct the biochemical abnormalities that are responsible for human illness. Chemotherapy is the area of pharmacology that deals with drugs used for the treatment of microbial infections and malignancies (cancer). Pharmacologists work to develop chemotherapeutic drugs that will selectively inhibit the growth of, or kill, the infectious agent or cancer cell without seriously impairing the normal functions of the host. Clinical pharmacology is the study of pharmacodynamics and pharmacokinetics in human beings. Clinical pharmacologists study how drugs work, how they interact with other drugs, how their effects can alter the disease process, and how disease can alter their effects. Clinical pharmacologists are in the forefront of research using date from the human genome project to determine how and why individuals respond differently to drugs. For more information about Clinical Pharmacology see the ASPET Division for Integrative Systems, Translational and Clinical Pharmacology Web pages. Drug Discovery, Drug Development, and Regulatory Affairs encompasses, but is not limited to; target discovery and validation, medicinal chemistry, combinatorial chemistry, molecular modeling and drug design, structure-pharmacological function Analysis Pharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Compartment-free methods are often more versatile in that they do not assume any specific compartmental model and produce accurate results also acceptable for bioequivalence studies. Noncompartmental analysis Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by area under the curve (AUC) methods, with the trapezoidal rule (numerical integration) the most common method. Due to the dependence on the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer time points are, the closer the trapezoids reflect the actual shape of the concentration-time curve.

Compartmental analysis Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental over some noncompartmental analyses is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. Compartment-free modeling based on curve stripping does not suffer this limitation. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination. The most complex PK models (called PBPK models) rely on the use of physiological information to ease development and validation. Bioanalytical methods

Bioanalytical methods are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma. Proper bioanalytical methods should be selective and sensitive. For exampleMicroscale Thermophoresis can be used to quantify how the biological matrix/liquid affects the affinity of a drug to its target.[8][9]
Mass spectrometry
Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often plasma or urine) and the need for high sensitivity to observe concentrations after a low dose and a long time period. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank samples taken before administration are important in determining background and insuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadraticssince the response of most mass spectrometers is less than linear across large concentration ranges.
[10][11][12]

There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation. Population pharmacokinetics Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest.
[14][15][16] [13]

Certain patient demographic, pathophysiological, and therapeutical features, such as body weight,

excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration

relationships. For example, steady-state concentrations of drugs eliminated mostly by the kidney are usually greater in patients suffering from renal failure than they are in patients with normal renal function receiving the same drug dosage. Population pharmacokinetics seeks to identify the measurable pathophysiologic factors that cause changes in the dose-concentration relationship and the extent of these changes so that, if such changes are associated with clinically significant shifts in the therapeutic index, dosage can be appropriately modified. Software packages used in population pharmacokinetics modeling include NONMEM, which was developed at the UCSF. Drug Metabolism and Disposition is the study of the pharmacokinetics of drugs as well as the enzymatic metabolism of drugs. For more information about Drug Metabolism see the ASPET Division for Drug Metabolism Web pages.

Endocrine pharmacology is the study of actions of drugs that are either hormones or hormone derivatives, or drugs that may modify the actions of normally secreted hormones. Endocrine pharmacologists are involved in solving mysteries concerning the nature and control of diseases of metabolic origin.

Neuropharmacology is the study of drugs that modify the functions of the nervous system, including the brain, spinal cord, and the nerves that communicate with all parts of the body. Neuropharmacologists study drug actions from a number of the different viewpoints. They may probe the neurochemical disorders underlying specific disease states to find new ways to use drugs in the treatment of disease. Alternatively, they may study drugs already in use to determine more precisely the neurophysiological or neurobiochemical changes that they produce. Other studies use drugs as tools to elucidate basic mechanisms of brain function, or to provide clues to the nature of disease processes. For more information about Neuropharmacology see the ASPET Division for Neuropharmacology Web pages.

Molecular pharmacology deals with the biochemical and biophysical characteristics of interactions between drug molecules and those of the cell. It is molecular biology applied to pharmacologic and toxicologic questions. The methods of molecular pharmacology include precise mathematical, physical, chemical and molecular biological techniques to understand how cells respond to hormones or pharmacologic agents, and how chemical structure correlates with biological activity. For more information about Molecular Pharmacology see the ASPET Division for Molecular Pharmacology Web pages.

Pharmacology Education involves undergraduate, graduate degree programs, and professional education in medical, pharmacy, and veterinary schools. For more information about Pharmacology Education see the ASPET Division for Pharmacology Educations Web pages. See the list of pharmacology training programs Web site links here. You may also find the pharmacology educational resources of interest.

Systems and Integrative Pharmacology is the study of drug action and toxicity in the whole animal. For more information about Systems and Integrative Pharmacology see the ASPET Division for Integrative Systems, Translational and Clinical Pharmacology Web pages.

Toxicology is the study of the adverse or toxic effects of drugs and other chemical agents. It is concerned not only with drugs used in the treatment of disease, but also with chemicals that may present household, environmental, or industrial hazards. Therapeutics focuses on the correlation of the actions and effects of drugs and other chemical agents with the physiological, biochemical, microbiological, immunological, or behavioral factors influencing disease. It also considers how disease may modify the pharmacokinetic properties of a drug by altering its absorption into the systemic circulation and/or its disposition. Each of these areas is closely interwoven with the subject matter and experimental techniques of physiology, biochemistry, cellular and molecular biology, microbiology, immunology, genetics, and pathology. For more information about Toxicology see the ASPET Division for Toxicology Web page.

Veterinary pharmacology concerns the use of drugs for diseases and health problems unique to animals. Pharmacology is the scientific study of the actions and interactions of drugs within a living organism. When external drugs, whether pharmaceutical or otherwise, enter the body of a person or animal they become the study of a pharmacologist. Pharmacology science encompasses the study of drugs that alter the functions of a given person or organism. These drugs can be medicinal or not. As an official science the study dates back to the 1840s and is not to be confused with pharmacy, which links health sciences with chemical sciences.

The job of the pharmacologist is to study the properties of a given drug. They must determine the make-up of the drug, how it came to be composed, and the interactions the drug has within the body of living organisms. The pharmacology student attempts to discover how it will react with the human body, how it will react with other substances, and what outcomes these reactions will have. They must determine the toxicology of the drug, as well as its possible uses in therapy and medicine; namely, how it will affect the biological functioning of the body.

Pharmacokinetics
From Wikipedia, the free encyclopedia
Pharmacokinetics may be simply defined as what the body does to the drug, as opposed topharmacodynamics which may be defined as what the drug does to the body.


Leslie Z. Benet, Pharmacokinetics: Basic Principles and Its Use as a Tool in Drug Metabolism, p.199 in: Drug Metabolism and Drug Toxicity, JR Mitchell and MG Horning (eds.), Raven Press, New York (1984).

Pharmacokinetics, sometimes abbreviated as PK, (from Ancient Greekpharmakon "drug" and kinetikos "to do with motion"; see chemical kinetics) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. The substances of interest include pharmaceutical agents, hormones, nutrients, and toxins. Pharmacokinetics is often studied in conjunction with pharmacodynamics. Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by metabolic enzymes such as CYP or UGT enzymes) and the effects and routes of excretion of the metabolites of the drug.[1]
ADME Pharmacokinetics is divided into several areas including the extent and rate of absorption, distribution, metabolism and excretion. This is commonly referred to as the ADME scheme:

Absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism (or Biotransformation) - the irreversible transformation of parent compounds into daughter metabolites.

Excretion (or Elimination) - the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.

Pharmacokinetics describes how the body affects a specific drug after administration. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the dose of administered drug. These may affect the absorption rate.
[2]

A fifth process, Liberation has been highlighted as playing an important role in pharmacokinetics:

[3][4]

Liberation - the process of release of drug from the formulation.

Hence LADME may sometimes be used in place of ADME in reference to the core aspects of pharmacokinetics.

Plasma concentration curves

Drugs injected intravenously are removed from the plasma through two primary mechanisms: (1) Distribution to body tissues and (2) metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see figure). Alpha phase: An initial phase of rapid decrease in plasma concentration. The decrease is primarily attribute to drug distribution from the central compartment (circulation) into the peripheral compartments (body tissues). This phase ends when an equilibrium of drug concentration is established between the central and peripheral compartments. Beta phase: A phase of gradual decrease in plasma concentration after the alpha phase. The decrease is primarily attribute to drug metabolism and excretion.
[5]

Additional phases (gamma, delta, etc.) are sometimes seen.

[6]

Metrics
The following are the most commonly measured pharmacokinetic metrics: Example value
[7]

Characteristic

Description

Abbreviation(s)

Formula

Dose

Loading dose(LD), orsteady state / maintenance dose (MD).

500 mg

design parameter

Dosing interval.

24 h

design parameter

Volume of distribution

The apparent volume in which a drug is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues.

6.0 L

Concentration

Initial or steady-state concentration of drug in plasma.

83.3 g/mL

The time required for the Biological half- concentration of the drug to life reach half of its original value.

12 h

Elimination rate constant

The rate at which drugs are removed from the body.

0.0578 h-1

Elimination rate

Rate of infusionrequired to balance elimination.

50 mg/h

Area under the curve

The integral of the concentration-time curve (after a single dose or in steady state).

1320 g/mLh

Clearance

The volume of plasma cleared of the drug per unit time.

0.38 L/h

Bioavailability

The fraction of drug that is absorbed.

0.8

Cmax

The peak plasma concentration of a drug after oral administration.

60.9 g/mL

direct measurement

tmax

Time to reach Cmax.

3.9 h

direct measurement

Cmin

The lowest (trough) concentration that a drug reaches before the next dose is administered.

27.7 g/mL

direct measurement

Fluctuation

Peak trough fluctuation within one dosing interval at steady state

41.8 %

where

edit

In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its clearance. In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started.
Analysis Pharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Compartment-free methods are often more versatile in that they do not assume any specific compartmental model and produce accurate results also acceptable for bioequivalence studies. Noncompartmental analysis Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by area under the curve (AUC) methods, with the trapezoidal rule (numerical integration) the most common method. Due to the dependence on the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer time points are, the closer the trapezoids reflect the actual shape of the concentration-time curve. [edit]Compartmental analysis Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental over some noncompartmental analyses is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper

model. Compartment-free modeling based on curve stripping does not suffer this limitation. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination. The most complex PK models (called PBPK models) rely on the use of physiological information to ease development and validation. [edit]Bioanalytical methods Bioanalytical methods are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma. Proper bioanalytical methods should be selective and sensitive. For exampleMicroscale Thermophoresis can be used to quantify how the biological matrix/liquid affects the affinity of a drug to its target. Mass spectrometry Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often plasma or urine) and the need for high sensitivity to observe concentrations after a low dose and a long time period. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank samples taken before administration are important in determining background and insuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadraticssince the response of most mass spectrometers is less than linear across large concentration ranges.
[10][11][12] [8][9]

There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation. Population pharmacokinetics Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest.
[14][15][16] [13]

Certain patient demographic, pathophysiological, and therapeutical features, such as body weight,

excretory and metabolic functions, and the presence of other therapies, can regularly alter dose-concentration relationships. For example, steady-state concentrations of drugs eliminated mostly by the kidney are usually greater in patients suffering from renal failure than they are in patients with normal renal function receiving the same drug dosage. Population pharmacokinetics seeks to identify the measurable pathophysiologic factors that cause changes in the dose-concentration relationship and the extent of these changes so that, if such changes are associated with clinically significant shifts in the therapeutic index, dosage can be appropriately modified.

Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect.[1] One dominant example is drug-receptor interactions as modeled by

where L=ligand (drug), R=receptor (attachment site), reaction dynamics that can be studied mathematically through tools such as free energy maps. Pharmacodynamics is often summarized as the study of what a drug does to the body, whereas pharmacokinetics is the study of what the body does to a drug. Pharmacodynamics is sometimes abbreviated as "PD", while pharmacokinetics can be referred to as "PK". Pharmacokinetics may be simply defined as what the body does to the drug, as opposed to pharmacodynamics which may be defined as what the drug does to the body. Effects on the body The majority of drugs either (a) mimic or inhibit normal physiological/biochemical processes or inhibit pathological processes in animals or (b) inhibit vital processes of endo- or ectoparasites and microbial organisms. There are 7 main drug actions:

stimulating action through direct receptor agonism and downstream effects depressing action through direct receptor agonism and downstream effects (ex.: inverse agonist) blocking/antagonizing action (as with silent antagonists), the drug binds the receptor but does not activate it stabilizing action, the drug seems to act neither as a stimulant or as a depressant (ex.: some drugs possess receptor activity that allows to stabilize general receptor activation, like buprenorphine in opioid dependent individuals or aripiprazole in schizophrenia, all depending on the dose and the recipient) exchanging/replacing substances or accumulating them to form a reserve (ex.: glycogen storage) direct beneficial chemical reaction as in free radical scavenging direct harmful chemical reaction which might result in damage or destruction of the cells, through induced toxic or lethal damage (cytotoxicity or irritation)

PRINCIPLES OF DRUG ADMINISTRATIONI . The Five Plus Five Rights of Drug Administration 5 Traditional Rights1 . r i g h t c l i e n t 2 . r i g h t d r u g 3 . r i g h t d o s e 4 . r i g h t t i m e 5 . r i g h t r o u t e 5 Additional Rights 1.right assessment 2.right documentation 3.clients right to education 4 . r i g h t e v a l u a t i o n 5.clients right to refuse A . R i g h t C l i e n t Nurse must do: verify client check ID bracelet & room number have client state his name

distinguish bw 2 clients with same last names B.Right Drug medication order may be prescribed by:a . P h y s i c i a n b . D e n t i s t c . P o d i a t r i s t d. Advanced practice registered nurse (APRN) Components of a drug order: 1.date & time the order is written 2.drug name (generic preferred) 3.drug dosage 4.frequency & duration of administration 5.any special instructions for withholding or adjusting dosage 6.physician or other health care providers signature or name if TO or VO 7.signature of licensed practitioner taking TO or VO Nurse must do: check med order is complete & legible. know general purpose or action, dosage & route of drug compare drug card with drug label three times .1.at time of contact with drug bottle/ co ntainer 2 . b e f o r e p o u r i n g d r u g 3 . a f t e r p o u r i n g drug 4 Categories of Drug Orders: 1.Standing Order / Routine Order ongoing order may have special instructions to base administration include PRN orders