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| {{mergefrom|Drug action|discuss=Talk:Pharmacodynamics#Merger proposal|date=November 2013}}
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| {{Quote box
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| |quote = '''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.<ref>
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| [http://bts.ucsf.edu/pspg/faculty/pages/benet.html 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).</ref> | |
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| '''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.<ref>{{cite journal |author=Lees P, Cunningham FM, Elliott J |title=Principles of pharmacodynamics and their applications in veterinary pharmacology |journal=J. Vet. Pharmacol. Ther. |volume=27 |issue=6 |pages=397–414 |year=2004 |pmid=15601436 |doi=10.1111/j.1365-2885.2004.00620.x}}</ref> One dominant example is drug-receptor interactions as modeled by
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| :<math>L + R \ \rightleftharpoons \ L\! \cdot \!R </math>
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| where ''L''=ligand (drug), ''R''=receptor (attachment site), [[reaction dynamics]] that can be studied mathematically through tools such as [[Thermodynamic free energy|free energy]] maps. Pharmacodynamics is often summarized as the study of what a [[medication|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". See [[PK/PD models]].
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| {{Quote box
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| |title = IUPAC definition
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| |quote = Branch of pharmacology concerned with pharmacological actions on living systems,<br/>including the reactions with and binding to cell constituents, and the biochemical<br/>and physiological consequences of these actions.
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| ''Note'': Modified from ref.<ref>{{cite book|title=Compendium of Chemical Terminology: IUPAC Recommendations|year=1997|publisher=Blackwell Science|location=Oxford|isbn=0865426848|edition=2nd|editor=Alan D. MacNaught, Andrew R. Wilkinson}}</ref>
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| <ref>{{cite journal|title=Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)|journal=[[Pure and Applied Chemistry]]|year=2012|volume=84|issue=2|pages=377-410|doi=10.1351/PAC-REC-10-12-04|url=http://pac.iupac.org/publications/pac/pdf/2012/pdf/8402x0377.pdf}}</ref>
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| }}
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| ==Effects on the body==
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| The majority of drugs either <br />
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| (a) mimic or inhibit normal physiological/biochemical processes or inhibit pathological processes in animals or <br />
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| (b) inhibit vital processes of endo- or ectoparasites and microbial organisms.
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| There are 7 main drug actions:
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| *[[Stimulation|stimulating action]] through direct [[Agonist|receptor agonism]] and downstream effects
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| *[[Depression (physiology)|depressing action]] through direct [[Agonist|receptor agonism]] and downstream effects (ex.: [[inverse agonist]])
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| *blocking/antagonizing action (as with [[Receptor antagonist|silent antagonists]]), the drug binds the receptor but does not activate it
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| *stabilizing action, the drug seems to act neither as a stimulant or as a depressant (ex.: some drugs possess receptor activity that allows them to stabilize general receptor activation, like [[buprenorphine]] in opioid dependent individuals or [[aripiprazole]] in schizophrenia, all depending on the dose and the recipient)
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| *exchanging/replacing substances or accumulating them to form a reserve (ex.: [[glycogen]] storage)
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| *direct beneficial chemical reaction as in [[Antioxidant#The oxidative challenge in biology|free radical scavenging]]
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| *direct harmful chemical reaction which might result in damage or destruction of the cells, through induced toxic or lethal damage ([[cytotoxicity]] or [[irritation]])
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| ===Desired activity===
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| The desired activity of a drug is mainly due to successful targeting of one of the following:
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| *[[Cellular membrane]] disruption
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| *[[Chemical reaction]] with downstream effects
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| *Interaction with [[enzyme]] proteins
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| *Interaction with [[structural]] proteins
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| *Interaction with [[Carrier-protein|carrier]] proteins
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| *Interaction with [[ion channel]]s
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| *[[Ligand binding]] to [[Receptor (biochemistry)|receptors]]:
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| **[[Hormone]] receptors
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| **[[Neuromodulator]] receptors
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| **[[Neurotransmitter]] receptors
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| [[General anesthetic]]s were once thought to work by disordering the neural membranes, thereby altering the Na<sup>+</sup> influx. [[Antacid]]s and [[chelating agent]]s combine chemically in the body. Enzyme-substrate binding is a way to alter the production or metabolism of key [[endogenous]] chemicals, for example [[aspirin]] irreversibly inhibits the enzyme [[cyclooxygenase|prostaglandin synthetase (cyclooxygenase)]] thereby preventing [[Inflammation|inflammatory]] response. [[Colchicine]], a drug for gout, interferes with the function of the structural protein [[tubulin]], while [[Digitalis]], a drug still used in heart failure, inhibits the activity of the carrier molecule, [[Na-K-ATPase pump]]. The widest class of drugs act as ligands which bind to receptors which determine cellular effects. Upon drug binding, receptors can elicit their normal action (agonist), blocked action (antagonist), or even action opposite to normal (inverse agonist).
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| In principle, a pharmacologist would aim for a target [[blood plasma|plasma]] concentration of the drug for a desired level of response. In reality, there are many factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and concentrations cannot be maintained with absolute consistency because of metabolic breakdown and excretory clearance. [[Genetics|Genetic]] factors may exist which would alter metabolism or drug action itself, and a patient's immediate status may also affect indicated dosage.
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| ===Undesirable effects===
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| Undesirable effects of a drug include:
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| *Increased probability of cell [[Mutagen|mutation]] ([[carcinogen]]ic activity)
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| *A multitude of simultaneous assorted actions which may be deleterious
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| *Interaction (additive, multiplicative, or metabolic)
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| *Induced physiological damage, or abnormal chronic conditions
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| ===Therapeutic window===
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| {{Main|Therapeutic window}}
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| The therapeutic window is the amount of a [[medication]] between the amount that gives an effect ([[effective dose (pharmacology)|effective dose]]) and the amount that gives more [[adverse effects]] than desired effects. For instance, medication with a small pharmaceutical window must be administered with care and control, e.g. by frequently measuring blood concentration of the drug, since it easily loses effects or gives adverse effects.
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| ===Duration of action===
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| The ''duration of action'' of a drug is the length of time that particular drug is effective.<ref name="pmid7352385">{{cite journal | author = Carruthers SG | title = Duration of drug action | journal = Am. Fam. Physician | volume = 21 | issue = 2 | pages = 119–26 |date=February 1980 | pmid = 7352385 | doi = | url = }}</ref> Duration of action is a function of several parameters including plasma [[biological half-life|half-life]], the time to equilibrate between plamsa and target compartments, and the off rate of the drug from its [[biological target]].<ref name="pmid20880390">{{cite journal | author = Vauquelin G, Charlton SJ | title = Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action | journal = Br. J. Pharmacol. | volume = 161 | issue = 3 | pages = 488–508 |date=October 2010 | pmid = 20880390 | pmc = 2990149 | doi = 10.1111/j.1476-5381.2010.00936.x }}</ref>
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| ==Receptor binding==
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| The binding of ligands (drug) to receptors is governed by the ''[[law of mass action]]'' which relates the large-scale status to the rate of numerous molecular processes. The rates of formation and un-formation can be used to determine the equilibrium concentration of bound receptors. The ''equilibrium dissociation constant'' is defined by:
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| :::<math>L + R \ \leftrightarrow \ L\! \cdot \!R </math> <math>K_d = \frac{[L][R]}{[L\! \cdot \!R]}</math>
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| where ''L''=ligand, ''R''=receptor, square brackets [] denote concentration. The fraction of bound receptors is
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| :::<math>Fraction \ Bound = \frac{[L\! \cdot \! R]}{[R]+[L\! \cdot \! R]} =\frac{1}{1+\frac{K_d}{[L]}}</math>
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| [[File:DoseResponse.png|thumb|320px|Semi-log plots of two agonists with different K<sub>d</sub>. The blue curve represents the ligand with greater potency.]]
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| This expression is one way to consider the effect of a drug, in which the response is related to the fraction of bound receptors. The fraction of bound receptors is known as occupancy. The relationship between occupancy and pharmacological response is usually non-linear. This explains the so-called ''receptor reserve'' phenomenon i.e. the concentration producing 50% occupancy is typically higher than the concentration producing 50% of maximum response. The receptor reserve phenomenon is the model that states there are excess receptors on the cell surface than what is necessary for full effect.
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| Often the response is determined as a function of ''log[L]'' to consider many orders of magnitude of concentration. However, there is no biological or physical theory which relates effects to the log of concentration. It is just convenient for graphing purposes. It is useful to note that 50% of the receptors are bound when ''[L]=K<sub>d</sub>'' .
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| The graph shown represents the conc-response for two hypothetical receptor agonists, plotted in a semi-log fashion. The curve toward the left represents a higher potency (potency arrow does not indicate direction of increase) since lower concentrations are needed for a given response. The effect increases as a function of concentration.
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| == Multicellular pharmacodynamics ==
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| The concept of pharmacodynamics has been expanded to include '''Multicellular Pharmacodynamics''' (MCPD). MCPD is the study of the static and dynamic properties and relationships between a set of drugs and a dynamic and diverse multicellular 4 dimensional organization. It is the study of the workings of a drug on a minimal multicellular system (mMCS), both ''in vivo'' and ''in silico''. '''Networked Multicellular Pharmacodynamics''' (Net-MCPD) further extends the concept of MCPD to model regulatory genomic networks together with signal transduction pathways, as part of a complex of interacting components in the cell.
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| == Toxicodynamics ==
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| Pharmacokinetics and pharmacodynamics are termed [[toxicokinetics]] and toxicodynamics in the field of [[ecotoxicology]]. Here, the focus is on toxic effects on a wide range of organisms. The corresponding models are called toxicokinetic-toxicodynamic models (more details can be found at [http://www.ecotoxmodels.org/research-publications-projects/toxicokinetic-toxicodynamic-models/ Ecotoxmodels.org]).
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| == See also ==
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| * [[Dose-response relationship]]
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| * [[Pharmacokinetics]]
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| * [[ADME]]
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| * [[Antimicrobial pharmacodynamics]]
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| * [[Pharmaceutical company]]
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| * [[Schild regression]]
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| ==References==
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| <references/>
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| ==External links==
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| * Vijay. (2003) [http://www.ingentaconnect.com/content/adis/pdr/2003/00000001/00000003/art00002 Predictive software for drug design and development]. Pharmaceutical Development and Regulation 1 ((3)), 159-168.
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| * Werner, E., [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14678738&query_hl=3 In silico multicellular systems biology and minimal genomes], DDT vol 8, no 24, pp 1121–1127, Dec 2003. (Introduces the concepts MCPD and Net-MCPD)
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| *Dr. David W. A. Bourne, OU College of Pharmacy [http://www.boomer.org/pkin/ Pharmacokinetic and Pharmacodynamic Resources].
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| {{Medicinal chemistry}}
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| {{Pharmacology}}
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| {{Portal bar|Pharmacy and Pharmacology}}
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| [[Category:Pharmacodynamics| ]]
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| [[Category:Pharmacy]]
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| [[Category:Medicinal chemistry]]
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