Pharmacology

Pharmacology is the science of medical drugs and medications,[1] including a substance's origin,
composition, pharmacokinetics, therapeutic use, and toxicology. More specifically, it is the study of the
interactions that occur between a living organism and chemicals that affect normal or abnormal
biochemical function.[2] If substances have medicinal properties, they are considered pharmaceuticals.
 Pharmacology

Diagrammatic representation of organ bath used

for studying the effect of isolated tissues

MeSH Unique ID D010600 (https://www.n

cbi.nlm.nih.gov/mesh/68
010600)

The field encompasses drug composition and properties, functions, sources, synthesis and drug design,
molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication,
molecular diagnostics, interactions, chemical biology, therapy, and medical applications and
antipathogenic capabilities. The two main areas of pharmacology are pharmacodynamics and
pharmacokinetics. Pharmacodynamics studies the effects of a drug on biological systems, and
pharmacokinetics studies the effects of biological systems on a drug. In broad terms, pharmacodynamics
discusses the chemicals with biological receptors, and pharmacokinetics discusses the absorption,
distribution, metabolism, and excretion (ADME) of chemicals from the biological systems.

Pharmacology is not synonymous with pharmacy and the two terms are frequently confused. Pharmacology,
a biomedical science, deals with the research, discovery, and characterization of chemicals which show
biological effects and the elucidation of cellular and organismal function in relation to these chemicals.
In contrast, pharmacy, a health services profession, is concerned with the application of the principles
learned from pharmacology in its clinical settings; whether it be in a dispensing or clinical care role. In
either field, the primary contrast between the two is their distinctions between direct-patient care,
pharmacy practice, and the science-oriented research field, driven by pharmacology.

Etymology
The word pharmacology is derived from Greek word φάρμακον, pharmakon, meaning "drug" or "poison",
together with another Greek word -λογία, logia with the meaning of "study of" or "knowledge of"[3][4] (cf.
the etymology of pharmacy). Pharmakon is related to pharmakos, the ritualistic sacrifice or exile of a
human scapegoat or victim in Ancient Greek religion.

The modern term pharmacon is used more broadly than the term drug because it includes endogenous
substances, and biologically active substances which are not used as drugs. Typically it includes
pharmacological agonists and antagonists, but also enzyme inhibitors (such as monoamine oxidase
inhibitors).[5]

History

Naturally derived opium from opium

poppies has been used as a drug since
before 1100 BCE.[6]
 Opium's major active constituent,
morphine, was first isolated in 1804
and is now known to act as an opioid
agonist.[7][8]

The origins of clinical pharmacology date back to the Middle Ages, with pharmacognosy and Avicenna's
The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on
the Antedotary of Nicholas.[9] Early pharmacology focused on herbalism and natural substances, mainly
plant extracts. Medicines were compiled in books called pharmacopoeias. Crude drugs have been used
since prehistory as a preparation of substances from natural sources. However, the active ingredient of
crude drugs are not purified and the substance is adulterated with other substances.

Traditional medicine varies between cultures and may be specific to a particular culture, such as in
traditional Chinese, Mongolian, Tibetan and Korean medicine. However much of this has since been
regarded as pseudoscience. Pharmacological substances known as entheogens may have spiritual and
religious use and historical context.

In the 17th century, the English physician Nicholas Culpeper translated and used pharmacological texts.
Culpeper detailed plants and the conditions they could treat. In the 18th century, much of clinical
pharmacology was established by the work of William Withering.[10] Pharmacology as a scientific discipline
did not further advance until the mid-19th century amid the great biomedical resurgence of that
period.[11] Before the second half of the nineteenth century, the remarkable potency and specificity of
the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference
to extraordinary chemical powers and affinities to certain organs or tissues.[12] The first pharmacology
department was set up by Rudolf Buchheim in 1847, at University of Tartu, in recognition of the need to
understand how therapeutic drugs and poisons produced their effects.[11] Subsequently, the first
pharmacology department in England was set up in 1905 at University College London.

Pharmacology developed in the 19th century as a biomedical science that applied the principles of
scientific experimentation to therapeutic contexts.[13] The advancement of research techniques
propelled pharmacological research and understanding. The development of the organ bath preparation,
where tissue samples are connected to recording devices, such as a myograph, and physiological
responses are recorded after drug application, allowed analysis of drugs' effects on tissues. The
development of the ligand binding assay in 1945 allowed quantification of the binding affinity of drugs
at chemical targets.[14] Modern pharmacologists use techniques from genetics, molecular biology,
biochemistry, and other advanced tools to transform information about molecular mechanisms and
targets into therapies directed against disease, defects or pathogens, and create methods for
preventive care, diagnostics, and ultimately personalized medicine.

Divisions
The discipline of pharmacology can be divided into many sub disciplines each with a specific focus.

Systems of the body

A variety of topics involved with

pharmacology, including neuropharmacology,
renal pharmacology, human metabolism,
intracellular metabolism, and intracellular
regulation

Pharmacology can also focus on specific systems comprising the body. Divisions related to bodily systems
study the effects of drugs in different systems of the body. These include neuropharmacology, in the
central and peripheral nervous systems; immunopharmacology in the immune system. Other divisions
include cardiovascular, renal and endocrine pharmacology. Psychopharmacology is the study of the use of
drugs that affect the psyche, mind and behavior (e.g. antidepressants) in treating mental disorders (e.g.
depression).[15][16] It incorporates approaches and techniques from neuropharmacology, animal behavior
and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of
action of psychoactive drugs. The related field of neuropsychopharmacology focuses on the effects of
drugs at the overlap between the nervous system and the psyche.
Pharmacometabolomics, also known as pharmacometabonomics, is a field which stems from metabolomics,
the quantification and analysis of metabolites produced by the body.[17][18] It refers to the direct
measurement of metabolites in an individual's bodily fluids, in order to predict or evaluate the
metabolism of pharmaceutical compounds, and to better understand the pharmacokinetic profile of a
drug.[17][18] Pharmacometabolomics can be applied to measure metabolite levels following the
administration of a drug, in order to monitor the effects of the drug on metabolic pathways.
Pharmacomicrobiomics studies the effect of microbiome variations on drug disposition, action, and
toxicity.[19] Pharmacomicrobiomics is concerned with the interaction between drugs and the gut
microbiome. Pharmacogenomics is the application of genomic technologies to drug discovery and further
characterization of drugs related to an organism's entire genome. For pharmacology regarding individual
genes, pharmacogenetics studies how genetic variation gives rise to differing responses to drugs.
Pharmacoepigenetics studies the underlying epigenetic marking patterns that lead to variation in an
individual's response to medical treatment.[20]

Clinical practice and drug discovery

A toxicologist working in a lab

Pharmacology can be applied within clinical sciences. Clinical pharmacology is the application of
pharmacological methods and principles in the study of drugs in humans.[21] An example of this is
posology, which is the study of how medicines are dosed.[22]

Pharmacology is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines
that focus on understanding the properties and actions of chemicals.[23] However, pharmacology
emphasizes the therapeutic effects of chemicals, usually drugs or compounds that could become drugs,
whereas toxicology is the study of chemical's adverse effects and risk assessment.[23]

Pharmacological knowledge is used to advise pharmacotherapy in medicine and pharmacy.

Drug discovery
Drug discovery is the field of study concerned with creating new drugs. It encompasses the subfields of
drug design and development.[24] Drug discovery starts with drug design, which is the inventive process
of finding new drugs.[25] In the most basic sense, this involves the design of molecules that are
complementary in shape and charge to a given biomolecular target.[26] After a lead compound has been
identified through drug discovery, drug development involves bringing the drug to the market.[24] Drug
discovery is related to pharmacoeconomics, which is the sub-discipline of health economics that
considers the value of drugs[27][28] Pharmacoeconomics evaluates the cost and benefits of drugs in
order to guide optimal healthcare resource allocation.[29] The techniques used for the discovery,
formulation, manufacturing and quality control of drugs discovery is studied by pharmaceutical
engineering, a branch of engineering.[30] Safety pharmacology specialises in detecting and investigating
potential undesirable effects of drugs.[31]

The drug discovery cycle

Development of medication is a vital concern to medicine, but also has strong economical and political
implications. To protect the consumer and prevent abuse, many governments regulate the manufacture,
sale, and administration of medication. In the United States, the main body that regulates
pharmaceuticals is the Food and Drug Administration; they enforce standards set by the United States
Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMA, and
they enforce standards set by the European Pharmacopoeia.
The metabolic stability and the reactivity of a library of candidate drug compounds have to be
assessed for drug metabolism and toxicological studies. Many methods have been proposed for
quantitative predictions in drug metabolism; one example of a recent computational method is
SPORCalc.[32] A slight alteration to the chemical structure of a medicinal compound could alter its
medicinal properties, depending on how the alteration relates to the structure of the substrate or
receptor site on which it acts: this is called the structural activity relationship (SAR). When a useful
activity has been identified, chemists will make many similar compounds called analogues, to try to
maximize the desired medicinal effect(s). This can take anywhere from a few years to a decade or more,
and is very expensive.[33] One must also determine how safe the medicine is to consume, its stability in
the human body and the best form for delivery to the desired organ system, such as tablet or aerosol.
After extensive testing, which can take up to six years, the new medicine is ready for marketing and
selling.[33]

Because of these long timescales, and because out of every 5000 potential new medicines typically only
one will ever reach the open market, this is an expensive way of doing things, often costing over 1 billion
dollars. To recoup this outlay pharmaceutical companies may do a number of things:[33]

Carefully research the demand for their

potential new product before spending an
outlay of company funds.[33]
Obtain a patent on the new medicine
preventing other companies from producing
that medicine for a certain allocation of
time.[33]
The inverse benefit law describes the relationship between a drugs therapeutic benefits and its
marketing.

When designing drugs, the placebo effect must be considered to assess the drug's true therapeutic
value.
Drug development uses techniques from medicinal chemistry to chemically design drugs. This overlaps
with the biological approach of finding targets and physiological effects.

Wider contexts
Pharmacology can be studied in relation to wider contexts than the physiology of individuals. For
example, pharmacoepidemiology concerns the variations of the effects of drugs in or between
populations, it is the bridge between clinical pharmacology and epidemiology.[34][35]
Pharmacoenvironmentology or environmental pharmacology is the study of the effects of used
pharmaceuticals and personal care products (PPCPs) on the environment after their elimination from the
body.[36] Human health and ecology are intimately related so environmental pharmacology studies the
environmental effect of drugs and pharmaceuticals and personal care products in the environment.[37]

Drugs may also have ethnocultural importance, so ethnopharmacology studies the ethnic and cultural
aspects of pharmacology.[38]

Emerging fields
Photopharmacology is an emerging approach in medicine in which drugs are activated and deactivated
with light. The energy of light is used to change for shape and chemical properties of the drug, resulting
in different biological activity.[39] This is done to ultimately achieve control when and where drugs are
active in a reversible manner, to prevent side effects and pollution of drugs into the environment.[40][41]
Theory of pharmacology

A trio of dose response curves. Dose response curves are studied extensively
in pharmacology.

The study of chemicals requires intimate knowledge of the biological system affected. With the
knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed
substantially. It has become possible, through molecular analysis of receptors, to design chemicals that
act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface
receptors (which modulate and mediate cellular signaling pathways controlling cellular function).

Chemicals can have pharmacologically relevant properties and effects. Pharmacokinetics describes the
effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics
describes the chemical's effect on the body (desired or toxic).
Systems, receptors and ligands

The cholinergic synapse. Targets in synapses can be

modulated with pharmacological agents. In this case,
cholinergics (such as muscarine) and anticholinergics (such
as atropine) target receptors; transporter inhibitors (such
as hemicholinium) target membrane transport proteins and
anticholinesterases (such as sarin) target enzymes.

Pharmacology is typically studied with respect to particular systems, for example endogenous
neurotransmitter systems. The major systems studied in pharmacology can be categorised by their ligands
and include acetylcholine, adrenaline, glutamate, GABA, dopamine, histamine, serotonin, cannabinoid and
opioid.

Molecular targets in pharmacology include receptors, enzymes and membrane transport proteins. Enzymes
can be targeted with enzyme inhibitors. Receptors are typically categorised based on structure and
function. Major receptor types studied in pharmacology include G protein coupled receptors, ligand gated
ion channels and receptor tyrosine kinases.
Network pharmacology is a subfield of pharmacology that combines principles from pharmacology, systems
biology, and network analysis to study the complex interactions between drugs and targets (e.g.,
receptors or enzymes etc.) in biological systems. The topology of a biochemical reaction network
determines the shape of drug dose-response curve[42] as well as the type of drug-drug interactions,[43]
thus can help designing efficient and safe therapeutic strategies. The topology Network pharmacology
utilizes computational tools and network analysis algorithms to identify drug targets, predict drug-drug
interactions, elucidate signaling pathways, and explore the polypharmacology of drugs.

Pharmacodynamics
Pharmacodynamics is defined as how the body reacts to the drugs. Pharmacodynamics theory often
investigates the binding affinity of ligands to their receptors. Ligands can be agonists, partial agonists
or antagonists at specific receptors in the body. Agonists bind to receptors and produce a biological
response, a partial agonist produces a biological response lower than that of a full agonist, antagonists
have affinity for a receptor but do not produce a biological response.

The ability of a ligand to produce a biological response is termed efficacy, in a dose-response profile it
is indicated as percentage on the y-axis, where 100% is the maximal efficacy (all receptors are occupied).

Binding affinity is the ability of a ligand to form a ligand-receptor complex either through weak
attractive forces (reversible) or covalent bond (irreversible), therefore efficacy is dependent on binding
affinity.

Potency of drug is the measure of its effectiveness, EC50 is the drug concentration of a drug that
produces an efficacy of 50% and the lower the concentration the higher the potency of the drug
therefore EC50 can be used to compare potencies of drugs.

Medication is said to have a narrow or wide therapeutic index, certain safety factor or therapeutic
window. This describes the ratio of desired effect to toxic effect. A compound with a narrow
therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound
with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below
its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require
therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most
anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at
doses used to kill tumors.
The effect of drugs can be described with Loewe additivity which is one of several common reference
models.[43]

Other models include the Hill equation, Cheng-Prusoff equation and Schild regression.

Pharmacokinetics
Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of
drugs.[44]

When describing the pharmacokinetic properties of the chemical that is the active ingredient or active
pharmaceutical ingredient (API), pharmacologists are often interested in L-ADME:

Liberation – How is the API disintegrated

(for solid oral forms (breaking down into
smaller particles), dispersed, or dissolved
from the medication?
Absorption – How is the API absorbed
(through the skin, the intestine, the oral
mucosa)?
Distribution – How does the API spread
through the organism?
 Metabolism – Is the API converted
chemically inside the body, and into which
substances. Are these active (as well)?
Could they be toxic?
Excretion – How is the API excreted
(through the bile, urine, breath, skin)?
Drug metabolism is assessed in pharmacokinetics and is important in drug research and prescribing.

Pharmacokinetics is the movement of the drug in the body, it is usually described as 'what the body
does to the drug' the physico-chemical properties of a drug will affect the rate and extent of
absorption, extent of distribution, metabolism and elimination. The drug needs to have the appropriate
molecular weight, polarity etc. in order to be absorbed, the fraction of a drug the reaches the systemic
circulation is termed bioavailability, this is simply a ratio of the peak plasma drug levels after oral
administration and the drug concentration after an IV administration(first pass effect is avoided and
therefore no amount drug is lost). A drug must be lipophilic (lipid soluble) in order to pass through
biological membranes this is true because biological membranes are made up of a lipid bilayer
(phospholipids etc.) Once the drug reaches the blood circulation it is then distributed throughout the
body and being more concentrated in highly perfused organs.
Administration, drug policy
and safety

Drug policy
In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for
the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:

1. The drug must be found to be effective

against the disease for which it is
seeking approval (where 'effective' means
only that the drug performed better
than placebo or competitors in at least
two trials).
2. The drug must meet safety criteria by
being subject to animal and controlled
human testing.
Gaining FDA approval usually takes several years. Testing done on animals must be extensive and must
include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The
dosage of any drug approved for use is intended to fall within a range in which the drug produces a
therapeutic effect or desired outcome.[45]

The safety and effectiveness of prescription drugs in the U.S. are regulated by the federal Prescription
Drug Marketing Act of 1987.

The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.

Medicare Part D is a prescription drug plan in the U.S.

The Prescription Drug Marketing Act (PDMA) is an act related to drug policy.

Prescription drugs are drugs regulated by legislation.

Societies and education

Societies and administration

The International Union of Basic and Clinical Pharmacology, Federation of European Pharmacological
Societies and European Association for Clinical Pharmacology and Therapeutics are organisations
representing standardisation and regulation of clinical and scientific pharmacology.

Systems for medical classification of drugs with pharmaceutical codes have been developed. These
include the National Drug Code (NDC), administered by Food and Drug Administration.;[46] Drug
Identification Number (DIN), administered by Health Canada under the Food and Drugs Act; Hong Kong
Drug Registration, administered by the Pharmaceutical Service of the Department of Health (Hong Kong)
and National Pharmaceutical Product Index in South Africa. Hierarchical systems have also been
developed, including the Anatomical Therapeutic Chemical Classification System (AT, or ATC/DDD),
administered by World Health Organization; Generic Product Identifier (GPI), a hierarchical classification
number published by MediSpan and SNOMED, C axis. Ingredients of drugs have been categorised by
Unique Ingredient Identifier.
Education
The study of pharmacology overlaps with biomedical sciences and is the study of the effects of drugs on
living organisms. Pharmacological research can lead to new drug discoveries, and promote a better
understanding of human physiology. Students of pharmacology must have a detailed working knowledge
of aspects in physiology, pathology, and chemistry. They may also require knowledge of plants as sources
of pharmacologically active compounds.[38] Modern pharmacology is interdisciplinary and involves
biophysical and computational sciences, and analytical chemistry. A pharmacist needs to be well-
equipped with knowledge on pharmacology for application in pharmaceutical research or pharmacy
practice in hospitals or commercial organisations selling to customers. Pharmacologists, however, usually
work in a laboratory undertaking research or development of new products. Pharmacological research is
important in academic research (medical and non-medical), private industrial positions, science writing,
scientific patents and law, consultation, biotech and pharmaceutical employment, the alcohol industry,
food industry, forensics/law enforcement, public health, and environmental/ecological sciences.
Pharmacology is often taught to pharmacy and medicine students as part of a Medical School curriculum.

See also

Biology
portal

Cosmeceuticals
List of abbreviations used in medical
prescriptions
List of pharmaceutical companies
 List of withdrawn drugs
Pharmaceutical company
Pharmaceutical formulation

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External links

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IUPHAR/BPS Guide to Pharmacology (http://
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Further reading

Foreman JC, Johansen T, Gibb AJ (2009).

Textbook of Receptor Pharmacology,
Second Edition (https://books.google.com/b
ooks?id=Y9bsUpefYW0C&pg=PA51) . CRC
Press. ISBN 9781439887578.
Brunton L (2011). Brunton LL, Chabner B,
Knollmann BC (eds.). Goodman and Gilman's
The Pharmacological Basis of Therapeutics
(12 ed.). New York: McGraw-Hill. ISBN 978-0-
07-162442-8.
 Whalen K (2014). Lippincott Illustrated
Reviews: Pharmacology.

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