Editing Pharmacology (section)

==Theory of pharmacology==
{{Expand section|date=July 2019}}[[File:Dose response antagonist.jpg|class=skin-invert-image|thumb|400px|right|A trio of [[dose response curve]]s. 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 [[receptor (biochemistry)|receptors]], to design chemicals that act on specific cellular signaling or [[metabolic pathway]]s 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===
{{Expand section|date=July 2019}}{{Main|Ligand (biochemistry)|List of drugs|Neurotransmitter}}
[[File:Cholinergic synapse.svg|class=skin-invert-image|thumb|300px|The [[acetylcholine|cholinergic]] synapse. Targets in synapses can be modulated with pharmacological agents. In this case, [[cholinergic]]s (such as [[muscarine]]) and [[anticholinergic]]s (such as [[atropine]]) target receptors; [[Reuptake modulator|transporter inhibitors]] (such as [[hemicholinium]]) target membrane transport proteins and [[anticholinesterase]]s (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 [[ligand (biochemistry)|ligand]]s and include [[acetylcholine]], [[adrenaline]], [[glutamate]], [[GABA]], [[dopamine]], [[histamine]], [[serotonin]], [[cannabinoid]] and [[opioid]].

Molecular targets in pharmacology include [[receptor (biochemistry)|receptor]]s, [[enzyme]]s and [[membrane transport protein]]s. 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 relationship|dose-response curve]]<ref>{{cite journal |last1=van Wijk |first1=Roeland |last2=Tans |first2=Sander J. |last3=Wolde |first3=Pieter Rein ten |last4=Mashaghi |first4=Alireza |title=Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology |journal=Scientific Reports |date=18 June 2015 |volume=5 |issue=1 |page=11376 |doi=10.1038/srep11376 |pmid=26087464 |pmc=5155565 |bibcode=2015NatSR...511376V }}</ref> as well as the type of drug-drug interactions,<ref name="Mehrad Babaei 2023">{{cite journal |last1=Babaei |first1=Mehrad |last2=Evers |first2=Tom M.J. |last3=Shokri |first3=Fereshteh |last4=Altucci |first4=Lucia |last5=de Lange |first5=Elizabeth C.M. |last6=Mashaghi |first6=Alireza |title=Biochemical reaction network topology defines dose-dependent Drug–Drug interactions |journal=Computers in Biology and Medicine |date=March 2023 |volume=155 |pages=106584 |doi=10.1016/j.compbiomed.2023.106584 |pmid=36805215 |hdl=1887/3632248 |hdl-access=free }}</ref> 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===
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Pharmacodynamics is defined as how the body reacts to the drugs. Pharmacodynamics theory often investigates the [[binding affinity]] of [[ligand (biochemistry)|ligand]]s to their receptors. Ligands can be [[agonist]]s, partial agonists or [[Receptor antagonist|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 [[Intrinsic activity|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 [[Van der Waals force|weak attractive forces]] (reversible) or [[covalent bond]] (irreversible), therefore efficacy is dependent on binding affinity.

[[Potency (pharmacology)|Potency]] of drug is the measure of its effectiveness, [[EC50|EC<sub>50</sub>]] 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 EC<sub>50</sub> 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 [[antiepileptic]]s, [[aminoglycoside]] [[antibiotics]]). Most anti-[[cancer]] drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill [[tumor]]s.

The effect of drugs can be described with [[Loewe additivity]] which is one of several common reference models.<ref name="Mehrad Babaei 2023"/>

Other models include the [[Hill equation (biochemistry)|Hill equation]], [[Cheng-Prusoff equation]] and [[Schild regression]].

===Pharmacokinetics===
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[[Pharmacokinetics]] is the study of the bodily absorption, distribution, metabolism, and excretion of drugs.<ref>{{cite web |url= https://www.merriam-webster.com/dictionary/pharmacokinetics |title= Pharmacokinetics |website= Merriam-Webster |access-date= July 16, 2019 |archive-date= 16 July 2019 |archive-url= https://web.archive.org/web/20190716151748/https://www.merriam-webster.com/dictionary/pharmacokinetics |url-status= live }}</ref>

When describing the pharmacokinetic properties of the chemical that is the active ingredient or [[Active ingredient|active pharmaceutical ingredient]] (API), pharmacologists are often interested in ''L-ADME'':
* [[Liberation (pharmacology)|Liberation]] – How is the API disintegrated (for solid oral forms (breaking down into smaller particles), dispersed, or dissolved from the medication?
* [[Absorption (digestive)|Absorption]] – How is the API absorbed (through the [[human skin|skin]], the [[intestine]], the [[oral mucosa]])?
* [[Distribution (pharmacology)|Distribution]] – How does the API spread through the organism?
* [[Drug metabolism|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 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.