Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, 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 Biochemistry function. If substances have medicinal properties, they are considered pharmaceuticals.
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, drug interaction, 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.
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).
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 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. 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, at University of Tartu, in recognition of the need to understand how therapeutic drugs and poisons produced their effects. 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. 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.
Pharmacometabolomics, also known as pharmacometabonomics, is a field which stems from metabolomics, the quantification and analysis of metabolites produced by the body. 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. 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. 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 Epigenetics marking patterns that lead to variation in an individual's response to medical treatment.
Pharmacology is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals. 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.
Pharmacological knowledge is used to advise pharmacotherapy in medicine and pharmacy.
Drug development 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 European Medicines Agency (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. 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.
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:
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.
Drugs may also have ethnocultural importance, so ethnopharmacology studies the ethnic and cultural aspects of pharmacology.
Epigenetic therapy may offer an alternative 'master switch' to gene therapy to introduce persistent changes to the phenotype. Aging is well-known to be measurable through epigenetic clock.
Drugs mays induce persistent changes. When they cause drugs to lose efficacy, it is called drug tolerance. On the other hand, they may introduce benign changes to the body. Psychoplastogen produce profound effects by regulating neuroplasticity. Psychostimulants prevent grey matter loss in ADHD patients, at therapeutic doses.
Key parameters in pharmacokinetics include:
This include :
Molecular targets in pharmacology include receptors, 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 as well as the type of drug-drug interactions, 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.
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 , aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill .
The effect of drugs can be described with Loewe additivity which is one of several common reference models.
Other models include the Hill equation, Cheng-Prusoff equation and Schild regression.
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:
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 that 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 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.
Therefore, drugs should be screened for off-target activity by gene expression profiling, in addition to conventional ligand binding, enzyme assays, etc.
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. 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.
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; 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 Identifiers.
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