| Pharmacology | |
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Diagrammatic representation of organ bath used for studying the effect of isolated tissues
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| MeSH Unique ID | D010600 |
A variety of topics involved with pharmacology, including neuropharmacology, renal pharmacology, human metabolism, intracellular metabolism, and intracellular regulation
Pharmacology is the branch of biology concerned with the study of drug action,
where a drug can be broadly defined as any man-made, natural, or
endogenous (from within the body) molecule which exerts a biochemical or
physiological effect on the cell, tissue, organ, or organism (sometimes
the word pharmacon is used as a term to encompass these endogenous and exogenous bioactive
species). More specifically, it is the study of the interactions that
occur between a living organism and chemicals that affect normal or
abnormal biochemical function. If substances have medicinal properties,
they are considered pharmaceuticals.
The field encompasses drug composition and properties, synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, toxicology, 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 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 are their distinctions between
direct-patient care, for pharmacy practice, and the science-oriented
research field, driven by pharmacology.
The origins of clinical pharmacology date back to the Middle Ages in 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. Clinical pharmacology owes much of its foundation to the work of William Withering.
Pharmacology as a scientific discipline did not further advance until
the mid-19th century amid the great biomedical resurgence of that
period. 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. The first pharmacology department was set up by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.
Early pharmacologists focused on natural substances, mainly plant
extracts. Pharmacology developed in the 19th century as a biomedical
science that applied the principles of scientific experimentation to
therapeutic contexts. Today pharmacologists use 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 preventative care, diagnostics, and
ultimately personalized medicine.
Etymology
The word "pharmacology" is derived from Greek φάρμακον, pharmakon, "drug, poison, spell" and -λογία, -logia "study of", "knowledge of" (cf. the etymology of pharmacy).
Divisions
The discipline of pharmacology can be divided into many sub disciplines each with a specific focus.
Clinical pharmacology
Clinical pharmacology is the basic science of pharmacology with an added focus on the application of pharmacological principles and methods in the medical clinic and towards patient care and outcomes.
Neuropharmacology
Neuropharmacology is the study of the effects of medication on central and peripheral nervous system functioning.
Psychopharmacology
Psychopharmacology, also known as behavioral pharmacology, is the study of the effects of medication on the psyche (psychology),
observing changed behaviors of the body and mind, and how molecular
events are manifest in a measurable behavioral form. Psychopharmacology
is an interdisciplinary field which studies behavioral effects of
psychoactive drugs. 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. Another goal of behavioral pharmacology is to
develop animal behavioral models to screen chemical compounds with
therapeutic potentials. People in this field (called behavioral
pharmacologists) typically use small animals (e.g. rodents) to study
psychotherapeutic drugs such as antipsychotics, antidepressants and
anxiolytics, and drugs of abuse such as nicotine, cocaine and
methamphetamine. Ethopharmacology (not to be confused with ethnopharmacology) is a term which has been in use since the 1960s and derives from the Greek word ἦθος ethos meaning character and "pharmacology" the study of drug actions and mechanism.
Cardiovascular pharmacology
Cardiovascular
pharmacology is the study of the effects of drugs on the entire
cardiovascular system, including the heart and blood vessels.
Pharmacogenetics
Pharmacogenetics is clinical testing of genetic variation that gives rise to differing response to drugs.
Pharmacogenomics
Pharmacogenomics is the application of genomic technologies to drug discovery and further characterization of older drugs.
Pharmacoepidemiology
Pharmacoepidemiology is the study of the effects of drugs in large numbers of people.
Safety pharmacology
Safety pharmacology
specialises in detecting and investigating potential undesirable
pharmacodynamic effects of new chemical entities (NCEs) on physiological
functions in relation to exposure in the therapeutic range and above.
Systems pharmacology
Systems pharmacology is the application of systems biology principles in the field of pharmacology.
Toxicology
Toxicology is the study of the adverse effects,
molecular targets, and characterization of drugs or any chemical
substance in excess (including those beneficial in lower doses).
Theoretical pharmacology
Theoretical
pharmacology is a relatively new and rapidly expanding field of
research activity in which many of the techniques of computational
chemistry, in particular computational quantum chemistry and the method
of molecular mechanics, are proving to be of great value. Theoretical
pharmacologists aim at rationalizing the relation between the activity
of a particular drug, as observed experimentally, and its structural
features as derived from computer experiments. They aim to find
structure—activity relations. Furthermore, on the basis of the structure
of a given organic molecule, the theoretical pharmacologist aims at
predicting the biological activity of new drugs that are of the same
general type as existing drugs. More ambitiously, it aims to predict
entirely new classes of drugs, tailor-made for specific purposes.
Posology
Posology
is the study of how medicines are dosed. This depends upon various
factors including age, climate, weight, sex, elimination rate of drug,
genetic polymorphism and time of administration. It is derived from the Greek words πόσος posos meaning "how much?" and -λογία -logia "study of".
Environmental pharmacology
Environmental pharmacology is a new discipline. Focus is being given to understand gene–environment interaction, drug-environment interaction and toxin-environment interaction. There is a close collaboration between environmental science and medicine in addressing these issues, as healthcare itself can be a cause of environmental damage or remediation.
Human health and ecology are intimately related. Demand for more
pharmaceutical products may place the public at risk through the
destruction of species. The entry of chemicals and drugs into the aquatic ecosystem is a more serious concern today. In addition, the production of some illegal drugs pollutes drinking water supply by releasing carcinogens. This field is intimately linked with Public Health fields.
Experimental pharmacology
Experimental pharmacology involves the study of pharmacology through bioassay, to test the efficacy and potency of a drug.
Scientific background
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).
A chemical has, from the pharmacological point-of-view, various properties. 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).
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)?
Medication is said to have a narrow or wide therapeutic index 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.
Medicine development and safety testing
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 and 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.
If the chemical structure of a medicinal compound is altered slightly,
this could slightly or dramatically alter the medicinal properties of
the compound depending on the level of alteration as it relates to the
structural composition of the substrate or receptor site on which it
exerts its medicinal effect, a concept referred to as the structural
activity relationship (SAR). This means that when a useful activity has
been identified, chemists will make many similar compounds called
analogues, in an attempt to maximize the desired medicinal effect(s) of
the compound. This development phase can take anywhere from a few years
to a decade or more and is very expensive.
These new analogues need to be developed. It needs to be
determined how safe the medicine is for human consumption, its stability
in the human body and the best form for delivery to the desired organ
system, like tablet or aerosol. After extensive testing, which can take
up to 6 years, the new medicine is ready for marketing and selling.
As a result of the long time required to develop analogues and
test a new medicine and the fact that 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:
- Carefully research the demand for their potential new product before spending an outlay of company funds.
- Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time.
Drug legislation and safety
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:
- 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).
- 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.
The safety and effectiveness of prescription drugs in the U.S. is 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.
Education
Students of pharmacology are trained as biomedical scientists,
studying the effects of drugs on living organisms. This can lead to new
drug discoveries, as well as a better understanding of the way in which
the human body works.
Students of pharmacology must have detailed working knowledge of
aspects in physiology, pathology and chemistry. During a typical degree
they will cover areas such as (but not limited to) biochemistry, cell
biology, basic physiology, genetics and the Central Dogma, medical microbiology, neuroscience, and depending on the department's interests, bio-organic chemistry, or chemical biology.
Modern Pharmacology is highly interdisciplinary. Graduate
programs accept students from most biological and chemical backgrounds.
With the increasing drive towards biophysical and computational research
to describe systems, pharmacologists may even consider themselves
mainly physical scientists. In many instances, Analytical Chemistry is
closely related to the studies and needs of pharmacological research.
Therefore, many institutions will include pharmacology under a Chemistry
or Biochemistry Department, especially if a separate Pharmacology Dept.
does not exist. What makes an institutional department independent of
another, or exist in the first place, is usually an artifact of
historical times.
Whereas a pharmacy student will eventually work in a pharmacy
dispensing medications, a pharmacologist will typically work within a
laboratory setting. Careers for a pharmacologist include academic
positions (medical and non-medical), governmental positions, 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.
