Drug interaction

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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]


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]


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.


  1. Anonymous (2015), 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.