Adverse drug reaction
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- 1 Overview
- 2 Classification
- 3 Mechanisms
- 4 Assessing causality
- 5 Monitoring bodies
- 6 Diagnosis
- 7 See also
- 8 References
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 medications. An ADR is a particular type of 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. The study of ADRs is the concern of the field known as pharmacovigilance.
ADRs may be classified by cause and severity.
- Type A: pharmacologically predictableddfd
- Type B: bizarre and unpredictable (or idiosyncratic)
- Type C: arising from chronic use
- Type D: delayed reaction
- Type E: end of dose reaction
- Type F: failure of therapy
- 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
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:
- Red (High Risk)
- Orange (Elevated Risk)
- Yellow (Guarded Risk)
- Blue (General Risk)
- Green (Low Risk)
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.
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
Comorbid disease states
Phase I reactions
Phase II reactions
Interactions with other drugs
The risk of drug interactions is increased with polypharmacy.
These interactions are usually transient and mild until a new steady state is achieved. These are mainly for drugs without much first-pass liver metabolism. The prinicple plasma proteins for drug binding are:
- α1-acid glycoprotein
Some drug interactions with warfarin are due to changes in protein binding.
Patients have abnormal metabolism by cytochrome P450 due to either inheriting abnormal alleles or due to drug interactions. Tables are available to check for drug interactions due to P450 interactions..
An example of synergism is two drugs that both prolong the QT interval.
- Note that an ADR should not be labeled as 'certain' unless the ADR abates with dechallenge and recurs with rechallenge are true.
A more complicated scale is the Naranjo algorithm.
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.
- EudraVigilance (European Union)
- Paradoxical reaction
- The Medical Letter on Drugs and Therapeutics
- Yellow Card Scheme (UK)
- Nebeker JR, Barach P, Samore MH (2004). "Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting". Ann. Intern. Med. 140 (10): 795–801. PMID 15148066.
- Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977:10.
- 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.
- "MedWatch - What Is A Serious Adverse Event?". Retrieved 2007-09-18.
- "'Traffic-light' medicine risk website to launch". The Guardian. 2007-10-02. Check date values in:
- Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 146
- "Clinical Drug Use". Retrieved 2007-09-18.
- Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA. 286 (18): 2270–9. PMID 11710893.
- Goldstein DB (2003). "Pharmacogenetics in the laboratory and the clinic". N. Engl. J. Med. 348 (6): 553–6. doi:10.1056/NEJMe020173. PMID 12571264.
- "Drug-Interactions.com". Retrieved 2007-09-18.
- Weinshilboum R (2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. doi:10.1056/NEJMra020021. PMID 12571261.
- Evans WE, McLeod HL (2003). "Pharmacogenomics--drug disposition, drug targets, and side effects". N. Engl. J. Med. 348 (6): 538–49. doi:10.1056/NEJMra020526. PMID 12571262.
- DeVane CL (2002). "Clinical significance of drug binding, protein binding, and binding displacement drug interactions". Psychopharmacology bulletin. 36 (3): 5–21. PMID 12473961.
- 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.OVID full text summary table at OVID
- 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.
- "Drug-Interactions.com". Retrieved 2007-09-18.
- "Dermatology Atlas".