Adverse drug reaction 1274833 221008126 2008-06-22T17:07:28Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. An '''adverse drug reaction''' (abbreviated '''ADR''') or '''adverse drug event''' (abbreviated '''ADE''') is an expression that describes the unwanted, negative consequences associated with the use of given [[medication]]s. An ADR is a particular type of [[Adverse effect (medicine)|adverse effect]]. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial.<ref name="pmid15148066">{{cite journal |author=Nebeker JR, Barach P, Samore MH |title=Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting |journal=Ann. Intern. Med. |volume=140 |issue=10 |pages=795–801 |year=2004 |pmid=15148066 |doi=}}</ref> The study of ADRs is the concern of the field known as ''[[pharmacovigilance]]''. ==Classification== ADRs may be classified by e.g. cause and severity. ===Cause=== *Type A: Augmented pharmacologic effects *Type B: Bizarre effects (or [[idiosyncratic drug reaction|idiosyncratic]]) *Type C: Chronic effects *Type D: Delayed effects *Type E: End-of-treatment effects *Type F: Failure of therapy Types A and B were proposed in the 1970s,<ref>Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977:10.</ref> and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.<ref>Aronson JK. Drug therapy. In: Haslett C, Chilvers ER, Boon NA, Colledge NR, Hunter JAA, eds. Davidson's principles and practice of medicine 19th ed. Edinburgh: Elsevier Science, 2002:147-63. ISBN 0-44307-035-0.</ref> ===Seriousness and Severity=== The American [[Food and Drug Administration]] defines a serious adverse event as one when the patient outcome is:<ref>{{cite web |url=http://www.fda.gov/medwatch/report/DESK/advevnt.htm |title=MedWatch - What Is A Serious Adverse Event? |accessdate=2007-09-18 |format= |work=}}</ref>: * Death * Life-Threatening * Hospitalization (initial or prolonged) * Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life. * Congenital Anomaly * - or - * Requires Intervention to Prevent Permanent Impairment or Damage Severity is a point on an arbitrary scale of intensity of the adverse event in question. The terms "severe" and "serious" when applied to adverse events are technically very different. They are easily confused but can not be used interchangeably, require care in usage. A headache is severe, if it causes intense pain. There are scales like "visual analog scale" that help us assess the severity. A headache, on the other hand, can hardly ever be serious, unless it also satisfies the criteria for seriousness, listed above. ===Overall Drug Risk=== While no official scale exists yet to communicate overall drug risk, the [[iGuard]] Drug Risk Rating System is a five color rating scale similar to the [[Homeland Security Advisory System]]<ref>{{cite news |title='Traffic-light' medicine risk website to launch |publisher=[[The Guardian]] |date=[[2007-10-02]] |url=http://www.guardian.co.uk/business/2007/oct/02/7}}</ref>: * Red (High Risk) * Orange (Elevated Risk) * Yellow (Guarded Risk) * Blue (General Risk) * Green (Low Risk) ===Location=== Adverse effects may be local, i.e. limited to a certain location, or systemic, where a medication has caused adverse effects throughout the [[systemic circulation]]. For instance, some [[ocular antihypertensive]]s cause systemic effects<ref name=Rang146> {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 146 </ref>, although they are administered locally as [[eye drop]]s, since a fraction escapes to the systemic circulation. ==Mechanisms== As research better explains the biochemistry of drug use, less ADRs are Type B and more are Type A. Common mechanisms are: * Abnormal pharmacokinetics due to ** genetic factors ** comorbid disease states * Synergistic effects between either ** a drug and a disease ** two drugs ===Abnormal pharmacokinetics=== ====Comorbid disease states==== Various diseases, especially those that cause [[renal failure|renal]] or [[liver failure|hepatic]] insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states.<ref>{{cite web |url=http://www.clinicaldruguse.com/ |title=Clinical Drug Use |accessdate=2007-09-18 |format= |work=}}</ref> ====Genetic factors==== Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation.<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |pmid=11710893 |doi=10.1001/jama.286.18.2270}}</ref><ref name="pmid12571264">{{cite journal |author=Goldstein DB |title=Pharmacogenetics in the laboratory and the clinic |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=553–6 |year=2003 |pmid=12571264 |doi=10.1056/NEJMe020173}}</ref> Pharmacogenomics is the study of the inherited basis for abnormal drug reactions. =====Phase I reactions===== Inheriting abnormal [[allele]]s of [[cytochrome]] [[cytochrome P450|P450]] can alter drug metabolism. Tables are available to check for drug interactions due to P450 interactions.<ref>{{cite web |url=http://medicine.iupui.edu/flockhart/ |title=Drug-Interactions.com |accessdate=2007-09-18 |format= |work=}}</ref>.<ref name="pmid12571261">{{cite journal |author=Weinshilboum R |title=Inheritance and drug response |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=529–37 |year=2003 |pmid=12571261 |doi=10.1056/NEJMra020021}}</ref> Inheriting abnormal [[Cholinesterase enzyme|butyrylcholinesterase]] ([[Cholinesterase enzyme|pseudocholinesterase]]) may affect metabolism of drugs such as [[succinylcholine]]<ref name="pmid12571262">{{cite journal |author=Evans WE, McLeod HL |title=Pharmacogenomics--drug disposition, drug targets, and side effects |journal=N. Engl. J. Med. |volume=348 |issue=6 |pages=538–49 |year=2003 |pmid=12571262 |doi=10.1056/NEJMra020526}}</ref> =====Phase II reactions===== Inheriting abnormal [[acetyltransferase|N-acetyltransferase]] which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as [[isoniazid]], [[hydralazine]], and [[procainamide]].<ref name="pmid12571262"/><ref name="pmid12571261"/> Inheriting abnormal [[Thiopurine methyltransferase|thiopurine S-methyltransferase]] may affect the metabolism of the [[thiopurine]] drugs [[mercaptopurine]] and [[azathioprine]].<ref name="pmid12571261"/> ====Interactions with other drugs==== The risk of [[drug interaction]]s is increased with [[polypharmacy]]. =====Protein binding===== These interactions are usually transient and mild until a new steady state is achieved.<ref name="pmid12473961">{{cite journal |author=DeVane CL |title=Clinical significance of drug binding, protein binding, and binding displacement drug interactions |journal=Psychopharmacology bulletin. |volume=36 |issue=3 |pages=5–21 |year=2002 |pmid=12473961 |doi=}}</ref><ref name="pmid11907485">{{cite journal |author=Benet LZ, Hoener BA |title=Changes in plasma protein binding have little clinical relevance |journal=Clin. Pharmacol. Ther. |volume=71 |issue=3 |pages=115–21 |year=2002 |pmid=11907485 |doi=10.1067/mcp.2002.121829}}[http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11907485.ui OVID full text] [http://gateway.ovid.com/ovidweb.cgi?T=JS&NEWS=N&PAGE=image&IMAGE=00003098-200203000-00001%7cTT2&D=ovft summary table at OVID]</ref> These are mainly for drugs without much first-pass liver metabolism. The prinicple plasma proteins for drug binding are:<ref name="pmid12369572">{{cite journal |author=Sands CD, Chan ES, Welty TE |title=Revisiting the significance of warfarin protein-binding displacement interactions |journal=The Annals of pharmacotherapy |volume=36 |issue=10 |pages=1642–4 |year=2002 |pmid=12369572 |doi=10.1345/aph.1A208|url=http://www.theannals.com/cgi/reprint/36/10/1642}}</ref> # [[albumin]] # α1-acid glycoprotein # lipoproteins Some drug interactions with [[warfarin]] are due to changes in protein binding.<ref name="pmid12369572"/> =====Cytochrome P450===== Patients have abnormal metabolism by [[cytochrome]] [[cytochrome P450|P450]] due to either inheriting abnormal [[allele]]s or due to drug interactions. Tables are available to check for drug interactions due to P450 interactions.<ref>{{cite web |url=http://medicine.iupui.edu/flockhart/ |title=Drug-Interactions.com |accessdate=2007-09-18 |format= |work=}}</ref>. ===Synergistic effects=== An example of synergism is two drugs that both prolong the [[QT interval]]. ==Assessing causality== A simple scale is available at [http://annals.org/cgi/content/full/140/10/795#T2 http://annals.org/cgi/content/full/140/10/795].<ref name="pmid15148066"/> An ADR should not be labeled as 'certain' unless the ADR abates with a [[challenge-dechallenge-rechallenge]] protocol. A more complicated scale is the [[Naranjo algorithm]]. ==Monitoring bodies== Many countries have official bodies that monitor drug safety and reactions. On an international level, the [[WHO]] runs the [[Uppsala Monitoring Centre]], and the [[European Union]] runs the [[European Medicines Agency]] (EMEA). In the [[United States]], the [[Food and Drug Administration]] (FDA) is responsible for monitoring post-marketing studies. ==See also== * [[EudraVigilance]] ([[European Union]]) * [[Paradoxical reaction]] * [[Polypharmacy]] * [[Toxicology]] * ''[[The Medical Letter on Drugs and Therapeutics]]'' * [[Yellow Card Scheme]] (UK) ==References== {{Reflist}} ==External link== *[http://www.adverse-drug-reaction.net The Adverse Drug Reaction Electronic System] {{flag|United States}} [[Category:Pharmacy]] [[Category:Pharmacology]] [[Category:Healthcare quality]] [[zh:药物不良反应]]