Editing Drug interaction (section)

=== Based on metabolism ===
[[File:CYP2C9 1OG2.png|thumb|200px|Diagram of cytochrome P450 [[CYP2C9|isoenzyme 2C9]] with the [[heme|haem]] group in the centre of the enzyme.]]

Many drug interactions are due to alterations in [[drug metabolism]].<ref name=GENENG15June2008>{{cite news | author=Elizabeth Lipp
 | title=Tackling Drug-Interaction Issues Early On | url=http://www.genengnews.com/articles/chitem.aspx?aid=2509
 | work=[[Genetic Engineering & Biotechnology News]] | publisher=[[Mary Ann Liebert, Inc.]] | pages=14, 16, 18, 20
 | date=2008-06-15 | access-date=2008-07-06
 | quote=(subtitle) Researchers explore a number of strategies to better predict drug responses in the clinic }}</ref> Further, human drug-metabolizing enzymes are typically activated through the engagement of [[nuclear receptor]]s.<ref name=GENENG15June2008/> One notable system involved in metabolic drug interactions is the enzyme system comprising the [[cytochrome P450 oxidase]]s.

==== CYP450 ====
[[Cytochrome P450]] is a very large family of [[hemeprotein|haemoprotein]]s (hemoproteins) that are characterized by their [[enzyme|enzymatic]] activity and their role in the metabolism of a large number of drugs.<ref>{{GoldBookRef|title=cytochrome P450|file=CT06821}} {{cite journal | vauthors = Danielson PB | title = The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans | journal = Current Drug Metabolism | volume = 3 | issue = 6 | pages = 561–97 | date = December 2002 | pmid = 12369887 | doi = 10.2174/1389200023337054 }}</ref> Of the various families that are present in humans, the most interesting in this respect are the 1, 2 and 3, and the most important enzymes are [[CYP1A2]], [[CYP2C9]], [[CYP2C19]], [[CYP2D6]], [[CYP2E1]] and [[CYP3A4]].<ref name="Nelson">Nelson D (2003). [http://drnelson.utmem.edu/P450lect.html Cytochrome P450s in humans] {{webarchive |url=https://web.archive.org/web/20090710050953/http://drnelson.utmem.edu/P450lect.html |date=July 10, 2009 }}. Consulted 9 May 2005.</ref>
The majority of the enzymes are also involved in the metabolism of [[endogenous]] substances, such as [[steroid]]s or [[sex hormones]], which is also important should there be interference with these substances. The function of the enzymes can either be stimulated ([[enzyme induction]]) or inhibited ([[enzyme inhibition]]).

==== Through enzymatic inhibition and induction ====
If a drug is metabolized by a CYP450 enzyme and drug B blocks the activity of these enzymes, it can lead to pharmacokinetic alterations. A. This alteration results in drug A remaining in the bloodstream for an extended duration, and eventually increase in concentration.{{Citation needed|date=November 2023}}

In some instances, the inhibition may reduce the therapeutic effect, if instead the metabolites of the drug is responsible for the effect.{{Citation needed|date=November 2023}}

Compounds that increase the efficiency of the enzymes, on the other hand, may have the opposite effect and increase the rate of metabolism. 

==== Examples of metabolism-based interactions ====
An example of this is shown in the following table for the [[CYP1A2]] enzyme, showing the substrates (drugs metabolized by this enzyme) and some inductors and inhibitors of its activity:<ref name="Nelson" />

{| class="wikitable" style="margin:1em auto;" width="100%"
|-
| colspan="3" style="text-align:center;" | '''Drugs related to CYP1A2'''
|-
! Substrates !! Inhibitors !! Inductors
|- style="vertical-align: top;"
|
* [[Caffeine]]
* [[Theophylline]]
* [[Phenacetin]]
* [[Clomipramine]]
* [[Clozapine]]
* [[Thioridazine]]
||
* [[Omeprazole]]
* [[Nicotine]]
* [[Cimetidine]]
* [[Ciprofloxacin]]
||
* [[Phenobarbital]]
* [[Fluvoxamine]]
* [[Venlafaxine]]
* [[Ticlopidine]]
|}

Some foods also act as inductors or inhibitors of enzymatic activity. The following table shows the most common:
{| class="wikitable" style="margin:1em auto;" width=100%
|-
|colspan="3" style="text-align:center;"| Foods and their influence on drug metabolism<ref>{{cite journal | vauthors = Bailey DG, Malcolm J, Arnold O, Spence JD | title = Grapefruit juice-drug interactions | journal = British Journal of Clinical Pharmacology | volume = 46 | issue = 2 | pages = 101–10 | date = August 1998 | pmid = 9723817 | pmc = 1873672 | doi = 10.1046/j.1365-2125.1998.00764.x }}<br/>Comment in: {{cite journal | vauthors = Mouly S, Paine MF | title = Effect of grapefruit juice on the disposition of omeprazole | journal = British Journal of Clinical Pharmacology | volume = 52 | issue = 2 | pages = 216–7 | date = August 2001 | pmid = 11488783 | pmc = 2014525 | doi = 10.1111/j.1365-2125.1978.00999.pp.x }}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="Marduga" /><ref>{{cite journal |author=Covarrubias-Gómez, A. |title=¿Qué se auto-administra su paciente?: Interacciones farmacológicas de la medicina herbal |journal=Revista Mexicana de Anestesiología |volume=28 |issue=1 |pages=32–42 |date=January–March 2005 |url=http://www.medigraphic.com/espanol/e-htms/e-rma/e-cma2005/e-cma05-1/em-cma051f.htm |archive-url=https://archive.today/20120629232743/http://www.medigraphic.com/espanol/e-htms/e-rma/e-cma2005/e-cma05-1/em-cma051f.htm |url-status=dead |archive-date=2012-06-29 |display-authors=etal }}</ref>
|-
! Food !! Mechanism !! Drugs affected
|-
|
* [[Avocado]]
* [[Brassicaceae|Brassica]]s (Brussels sprouts, broccoli, cabbage)
|Enzymatic inductor
|[[Acenocoumarol]], [[warfarin]]
|-
|[[Grapefruit]] juice
|Enzymatic inhibition
|
* [[Calcium channel blocker]]s: [[nifedipine]], [[felodipine]], [[nimodipine]], [[amlodipine]]
* [[Cyclosporine]], [[tacrolimus]]
* [[Terfenadine]], [[astemizole]]
* [[Cisapride]], [[pimozide]]
* [[Carbamazepine]], [[saquinavir]], [[midazolam]], [[alprazolam]], [[triazolam]]
{{main|Grapefruit drug interactions}}
|-
|[[Soybean|Soya]]
|Enzymatic inhibition
|[[Clozapine]], [[haloperidol]], [[olanzapine]], [[caffeine]], [[Non-steroidal anti-inflammatory drug|NSAIDs]], [[phenytoin]], [[zafirlukast]], [[warfarin]]
|-
|[[Garlic]]
|Increases antiplatelet activity
|
* [[Anticoagulant]]s
* [[Non-steroidal anti-inflammatory drug|NSAIDs]], [[acetylsalicylic acid]]
|-
|[[Ginseng]]
|To be determined
|[[Warfarin]], [[heparin]], [[aspirin]] and [[Non-steroidal anti-inflammatory drug|NSAIDs]]
|-
|''[[Ginkgo biloba]]''
|Strong inhibitor of platelet aggregation factor
|[[Warfarin]], [[aspirin]] and [[Non-steroidal anti-inflammatory drug|NSAIDs]]
|-
|''[[Hypericum perforatum]]'' (St John's wort)
|Enzymatic inductor (CYP450)
|Warfarin, [[digoxin]], [[theophylline]], cyclosporine, [[phenytoin]] and antiretrovirals
|-
|[[Ephedra (medicine)|Ephedra]]
|Receptor level agonist
|[[MAOI]], central nervous system stimulants, alkaloids [[ergotamine]]s and [[xanthine]]s
|-
|Kava (''Piper methysticum'')
|Unknown
|[[Levodopa]]
|-
|[[Ginger]]
|Inhibits thromboxane synthetase (''in vitro'')
|Anticoagulants
|-
|Chamomile
|Unknown
|[[Benzodiazepine]]s, [[barbiturate]]s and [[opioid]]s
|-
|[[Crataegus|Hawthorn]]
|Unknown
|Beta-adrenergic antagonists, [[cisapride]], digoxin, [[quinidine]]
|}