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In [[pharmacology]], '''drug interactions''' are "the action of a drug that may affect the activity, metabolism, or [[drug toxicity|toxicity]] of another drug."<ref>{{MeSH}}</ref>
In [[pharmacology]], '''drug interactions''' are "the action of a drug that may affect the activity, metabolism, or [[drug toxicity|toxicity]] of another drug."<ref>{{MeSH}}</ref>


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===Cytochrome P450===
===Cytochrome P450===
Patients have abnormal metabolism by [[cytochrome P-450]] due to either inheriting abnormal [[allele]]s or due to drug interactions. Tables are available to check for drug interactions due to [[cytochrome P-450]] interactions.<ref>{{cite web |url=http://medicine.iupui.edu/flockhart/ |title=Drug-Interactions.com |accessdate=2007-09-18 |format= |work=}}</ref>.
Patients have abnormal metabolism by [[cytochrome P-450]] due to either inheriting abnormal [[allele]]s or due to drug interactions. Tables are available to check for drug interactions due to [[cytochrome P-450]] interactions.<ref>{{cite web |url=http://medicine.iupui.edu/flockhart/ |title=Drug-Interactions.com |accessdate=2007-09-18 |format= |work=}}</ref>.
===Gastrointestinal absorption===
Medicines may change the [[biological availability]] of other medications via changes in [[absorption]]. Examples are
* [[proton pump inhibitor]]s and [[aspirin]]<ref name="pmid21562004">{{cite journal| author=Charlot M, Grove EL, Hansen PR, Olesen JB, Ahlehoff O, Selmer C et al.| title=Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. | journal=BMJ | year= 2011 | volume= 342 | issue=  | pages= d2690 | pmid=21562004 | doi=10.1136/bmj.d2690 | pmc=PMC3092520 | url= }} </ref>
* [[proton pump inhibitor]]s and [[alendronate]]<ref name="pmid21321287">{{cite journal| author=Abrahamsen B, Eiken P, Eastell R| title=Proton pump inhibitor use and the antifracture efficacy of alendronate. | journal=Arch Intern Med | year= 2011 | volume= 171 | issue= 11 | pages= 998-1004 | pmid=21321287 | doi=10.1001/archinternmed.2011.20 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21321287  }} </ref>
===Renal clearance===
Drugs may compete for renal excretion.<ref name="pmid3593625">{{cite journal| author=Somogyi A, Stockley C, Keal J, Rolan P, Bochner F| title=Reduction of metformin renal tubular secretion by cimetidine in man. | journal=Br J Clin Pharmacol | year= 1987 | volume= 23 | issue= 5 | pages= 545-51 | pmid=3593625 | doi= | pmc=PMC1386190 | url= }} </ref>


==Prevention==
==Prevention==
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* [[Sensitivity and specificity|Sensitivity]] 84% to 100%
* [[Sensitivity and specificity|Sensitivity]] 84% to 100%
* [[Sensitivity and specificity|Specificity]] 68% to 95%
* [[Sensitivity and specificity|Specificity]] 68% to 95%
Lower sensitivities have been reported using a different test collection of interactions.<ref name="pmid15142922">{{cite journal |author=Fernando B, Savelyich BS, Avery AJ, ''et al.'' |title=Prescribing safety features of general practice computer systems: evaluation using simulated test cases |journal=BMJ |volume=328 |issue=7449 |pages=1171–2 |year=2004 |month=May |pmid=15142922 |pmc=411094 |doi=10.1136/bmj.328.7449.1171 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=15142922 |issn=}}</ref>


====List of resources====
====List of resources====
* [http://www.firstdatabank.com/products/evaluations/ First Databank]
The concordance between alerts generated by major resources is low.<ref name="pmid15098847">{{cite journal |author=Abarca J, Malone DC, Armstrong EP, ''et al.'' |title=Concordance of severity ratings provided in four drug interaction compendia |journal=J Am Pharm Assoc (2003) |volume=44 |issue=2 |pages=136–41 |year=2004 |pmid=15098847 |doi= |url=http://japha.metapress.com/openurl.asp?genre=article&issn=1544-3191&volume=44&issue=2&spage=136 |issn=}}</ref>
* [http://www.firstdatabank.com/products/evaluations/ First Databank's Evaluations of Drug Interactions]
* Facts & Comparisons®
** [http://www.factsandcomparisons.com/Products/Product.aspx?id=117 Drug Interaction Facts]
** [http://www.factsandcomparisons.com/Products/Product.aspx?id=118 Drug Interactions: Analysis and Management]
* [http://www.micromedex.com/products/drugreax/ MicroMedex's DRUG-REAX]
* http://www.gsm.com
* http://www.epocrates.com
** http://drug-interactions.com - [[Cytochrome P-450]]
* [http://www.certs.hhs.gov/centers/centers.htm Centers for Education & Research on Therapeutics] (CERTs). These are sponsored in the [[United States of America]] by the [[Agency for Healthcare Research and Quality]].
** http://www.arizonacert.org - [[QT interval]] prolongation
** http://www.hit-cert.org/ - role of information technology
** [http://www.chicagopatientsafety.org/CPSF_initiatives/TOP-MED_CERT.htm University of Illinois–Chicago] - Tools for optimizing prescribing


===Medical order entry system===
===Medical order entry system===
{{main|Medical order entry system}}
{{main|Medical order entry system}}
Perhaps due to imperfect specificity of drug interaction resources, health care providers overide 49% to 96% of alerts.<ref name="pmid16357358">{{cite journal |author=van der Sijs H, Aarts J, Vulto A, Berg M |title=Overriding of drug safety alerts in computerized physician order entry |journal=J Am Med Inform Assoc |volume=13 |issue=2 |pages=138–47 |year=2006 |pmid=16357358 |pmc=1447540 |doi=10.1197/jamia.M1809 |url=http://www.jamia.org/cgi/pmidlookup?view=long&pmid=16357358 |issn=}}</ref>
Perhaps due to imperfect specificity and information of drug interaction resources, health care providers do not always find alerts to be useful<ref name="pmid17068346">{{cite journal |author=Ko Y, Abarca J, Malone DC, ''et al.'' |title=Practitioners' views on computerized drug-drug interaction alerts in the VA system |journal=J Am Med Inform Assoc |volume=14 |issue=1 |pages=56–64 |year=2007 |pmid=17068346 |pmc=2215077 |doi=10.1197/jamia.M2224 |url=http://www.jamia.org/cgi/pmidlookup?view=long&pmid=17068346 |issn=}}</ref> overide 49% to 96% of alerts.<ref name="pmid16357358">{{cite journal |author=van der Sijs H, Aarts J, Vulto A, Berg M |title=Overriding of drug safety alerts in computerized physician order entry |journal=J Am Med Inform Assoc |volume=13 |issue=2 |pages=138–47 |year=2006 |pmid=16357358 |pmc=1447540 |doi=10.1197/jamia.M1809 |url=http://www.jamia.org/cgi/pmidlookup?view=long&pmid=16357358 |issn=}}</ref>


Efforts are being made to improve drug safety alerts.<ref name="pmid16329715">{{cite journal |author=van Roon EN, Flikweert S, le Comte M, ''et al.'' |title=Clinical relevance of drug-drug interactions : a structured assessment procedure |journal=Drug Saf |volume=28 |issue=12 |pages=1131–9 |year=2005 |pmid=16329715 |doi= |url= |issn=}}</ref>
Efforts are being made to improve drug safety alerts by structuring<ref name="pmid16329715">{{cite journal |author=van Roon EN, Flikweert S, le Comte M, ''et al.'' |title=Clinical relevance of drug-drug interactions : a structured assessment procedure |journal=Drug Saf |volume=28 |issue=12 |pages=1131–9 |year=2005 |pmid=16329715 |doi= |url= |issn=}}</ref> and tiering<ref name="pmid18952941">{{cite journal |author=Paterno MD, Maviglia SM, Gorman PN, ''et al.'' |title=Tiering drug-drug interaction alerts by severity increases compliance rates |journal=J Am Med Inform Assoc |volume=16 |issue=1 |pages=40–6 |year=2009 |pmid=18952941 |pmc=2605599 |doi=10.1197/jamia.M2808 |url=http://www.jamia.org/cgi/pmidlookup?view=long&pmid=18952941 |issn=}}</ref> information.


==References==
==References==
<references/>
<references/>

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In pharmacology, drug interactions are "the action of a drug that may affect the activity, metabolism, or toxicity of another drug."[1]

Mechanisms

Protein binding

These interactions are usually transient and mild until a new steady state is achieved.[2][3] These are mainly for drugs without much first-pass liver metabolism. The principle plasma proteins for drug binding are:[4]

  1. albumin
  2. α1-acid glycoprotein
  3. lipoproteins

Some drug interactions with warfarin are due to changes in protein binding.[4]

Cytochrome P450

Patients have abnormal metabolism by cytochrome P-450 due to either inheriting abnormal alleles or due to drug interactions. Tables are available to check for drug interactions due to cytochrome P-450 interactions.[5].

Gastrointestinal absorption

Medicines may change the biological availability of other medications via changes in absorption. Examples are

Renal clearance

Drugs may compete for renal excretion.[8]

Prevention

Resources about drug interactions

In detecting drug-drug interactions, the accuracy of software used by hospital pharmacies range from:[9][10]

In detecting drug-drug interactions, the accuracy of PDA-based software range from:[11]

Lower sensitivities have been reported using a different test collection of interactions.[12]

List of resources

The concordance between alerts generated by major resources is low.[13]

Medical order entry system

For more information, see: Medical order entry system.

Perhaps due to imperfect specificity and information of drug interaction resources, health care providers do not always find alerts to be useful[14] overide 49% to 96% of alerts.[15]

Efforts are being made to improve drug safety alerts by structuring[16] and tiering[17] information.

References

  1. ↑ Anonymous (2024), Drug interaction (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ DeVane CL (2002). "Clinical significance of drug binding, protein binding, and binding displacement drug interactions". Psychopharmacology bulletin. 36 (3): 5–21. PMID 12473961. [e]
  3. ↑ Benet LZ, Hoener BA (2002). "Changes in plasma protein binding have little clinical relevance". Clin. Pharmacol. Ther. 71 (3): 115–21. DOI:10.1067/mcp.2002.121829. PMID 11907485. Research Blogging. OVID full text summary table at OVID
  4. ↑ 4.0 4.1 Sands CD, Chan ES, Welty TE (2002). "Revisiting the significance of warfarin protein-binding displacement interactions". The Annals of pharmacotherapy 36 (10): 1642–4. PMID 12369572. [e]
  5. ↑ Drug-Interactions.com. Retrieved on 2007-09-18.
  6. ↑ Charlot M, Grove EL, Hansen PR, Olesen JB, Ahlehoff O, Selmer C et al. (2011). "Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study.". BMJ 342: d2690. DOI:10.1136/bmj.d2690. PMID 21562004. PMC PMC3092520. Research Blogging.
  7. ↑ Abrahamsen B, Eiken P, Eastell R (2011). "Proton pump inhibitor use and the antifracture efficacy of alendronate.". Arch Intern Med 171 (11): 998-1004. DOI:10.1001/archinternmed.2011.20. PMID 21321287. Research Blogging.
  8. ↑ Somogyi A, Stockley C, Keal J, Rolan P, Bochner F (1987). "Reduction of metformin renal tubular secretion by cimetidine in man.". Br J Clin Pharmacol 23 (5): 545-51. PMID 3593625. PMC PMC1386190. [e]
  9. ↑ 9.0 9.1 9.2 Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP (June 2006). "Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies". J Manag Care Pharm 12 (5): 383–9. PMID 16792445. [e]
  10. ↑ 10.0 10.1 10.2 Hazlet TK, Lee TA, Hansten PD, Horn JR (2001). "Performance of community pharmacy drug interaction software". J Am Pharm Assoc (Wash) 41 (2): 200–4. PMID 11297332. [e]
  11. ↑ Robinson RL, Burk MS (March 2004). "Identification of drug-drug interactions with personal digital assistant-based software". Am. J. Med. 116 (5): 357–8. DOI:10.1016/j.amjmed.2003.09.025. PMID 14984827. Research Blogging.
  12. ↑ Fernando B, Savelyich BS, Avery AJ, et al. (May 2004). "Prescribing safety features of general practice computer systems: evaluation using simulated test cases". BMJ 328 (7449): 1171–2. DOI:10.1136/bmj.328.7449.1171. PMID 15142922. PMC 411094. Research Blogging.
  13. ↑ Abarca J, Malone DC, Armstrong EP, et al. (2004). "Concordance of severity ratings provided in four drug interaction compendia". J Am Pharm Assoc (2003) 44 (2): 136–41. PMID 15098847. [e]
  14. ↑ Ko Y, Abarca J, Malone DC, et al. (2007). "Practitioners' views on computerized drug-drug interaction alerts in the VA system". J Am Med Inform Assoc 14 (1): 56–64. DOI:10.1197/jamia.M2224. PMID 17068346. PMC 2215077. Research Blogging.
  15. ↑ van der Sijs H, Aarts J, Vulto A, Berg M (2006). "Overriding of drug safety alerts in computerized physician order entry". J Am Med Inform Assoc 13 (2): 138–47. DOI:10.1197/jamia.M1809. PMID 16357358. PMC 1447540. Research Blogging.
  16. ↑ van Roon EN, Flikweert S, le Comte M, et al. (2005). "Clinical relevance of drug-drug interactions : a structured assessment procedure". Drug Saf 28 (12): 1131–9. PMID 16329715. [e]
  17. ↑ Paterno MD, Maviglia SM, Gorman PN, et al. (2009). "Tiering drug-drug interaction alerts by severity increases compliance rates". J Am Med Inform Assoc 16 (1): 40–6. DOI:10.1197/jamia.M2808. PMID 18952941. PMC 2605599. Research Blogging.
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