Side effect explained

In medicine, a side effect is an effect, whether therapeutic or adverse, that is unintended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.

Occasionally, drugs are prescribed or procedures are performed for their side effects; in that case, said side effect ceases to be a side effect and is now an intended effect.^[1] For instance, X-rays were historically (and are currently) used as an imaging technique; the discovery of their oncolytic capability led to their employ in radiotherapy (ablation of malignant tumours).

Frequency of side effects

The World Health Organization and other health organisations characterise the probability of experiencing side effects as:^{[2] [3]}

• Very common, ≥ ¹⁄₁₀
• Common (frequent), ¹⁄₁₀ to ¹⁄₁₀₀
• Uncommon (infrequent), ¹⁄₁₀₀ to ¹⁄₁₀₀₀
• Rare, ¹⁄₁₀₀₀ to ¹⁄₁₀₀₀₀
• Very rare, < ¹⁄₁₀₀₀₀

The European Commission recommends that the list should contain only effects where "at least a reasonable possibility" exists that it is caused by the drug and the frequency "should represent crude incidence rates (and not differences or relative risks calculated against placebo or other comparator)".^[4] That is, the frequency describes how often symptoms appear after taking the drug, not caused by the drug. Both health care providers^[5] and lay people^[6] misinterpret the frequency of side effects as describing the increase in frequency caused by the drug.

Examples of therapeutic side effects

See also: Serendipity.

• Bevacizumab (Avastin), used to slow the growth of blood vessels, has been used against dry age-related macular degeneration, as well as macular edema from diseases such as diabetic retinopathy and central retinal vein occlusion.^[7]
• Buprenorphine has been shown experimentally (1982–1995) to be effective against severe, refractory depression.^{[8] [9]}
• Bupropion (Wellbutrin), an anti-depressant, is also used as a smoking cessation aid; this indication was later approved, and the name of the smoking cessation product is Zyban. In Ontario, Canada, smoking cessation drugs are not covered by provincial drug plans; elsewhere, Zyban is priced higher than Wellbutrin, despite being the same drug. Therefore, some physicians prescribe Wellbutrin for both indications.
• Carbamazepine is an approved treatment for bipolar disorder and epileptic seizures, but it has side effects useful in treating attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, neuromyotonia, and post-traumatic stress disorder.^[10]
• Dexamethasone and betamethasone in premature labor, to enhance pulmonary maturation of the fetus.^[11]
• Doxepin has been used to treat angioedema and severe allergic reactions due to its strong antihistamine properties.^[12]
• Gabapentin, approved for treatment of seizures and postherpetic neuralgia in adults, has side effects which are useful in treating bipolar disorder, essential tremor, hot flashes, migraine prophylaxis, neuropathic pain syndromes, phantom limb syndrome, and restless leg syndrome.^[13]
• Hydroxyzine, an antihistamine, is also used as an anxiolytic.
• Magnesium sulfate in obstetrics for premature labor and preeclampsia.
• Methotrexate (MTX), approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy.^[14]
• The SSRI medication sertraline is approved as an antidepressant but delays conjugal climax in men, and thus may be supplied to those in which climax is premature.^[15]
• Sildenafil was originally intended for pulmonary hypertension; subsequently, it was discovered that it also produces erections, for which it was later marketed.
• Terazosin, an α₁-adrenergic antagonist approved to treat benign prostatic hyperplasia (enlarged prostate) and hypertension, is (one of several drugs) used off-label to treat drug induced diaphoresis and hyperhidrosis (excessive sweating).^{[16] [17]}

Examples of adverse effects

See main article: Adverse effect.

• Echinacea – numerous potential reactions may occur, including allergic reactions, hives, swelling of the face, aching muscles and gastrointestinal discomfort.^[18]
• Feverfew – pregnant women should avoid using this herb, as it can trigger uterine contractions which could lead to premature labour or miscarriage.^[19]
• Asteraceae plants – which include feverfew, echinacea, dandelion and chamomile. Side effects include allergic dermatitis and hay fever.

See also

• Adverse drug reaction (ADR), a harmful unintended result caused by taking medication
• Combined drug intoxication
• Conservative management
• Drug-drug interaction (DDI), an alteration of the action of a drug caused by the administration of other drugs
• Paradoxical reaction, an effect of a substance opposite to what would usually be expected
• Pharmacogenetics, the use of genetic information to determine which type of drugs will work best for a patient
• Unintended consequences

External links

• Web site: MedEffect Canada . Health Canada . 13 July 2011 .
• Web site: Definitions . World Health Organization .

Notes and References

1. Due A . What are side effects? . European Journal for Philosophy of Science . 13 . 1 . 16 . 2023 . 36936702 . 10006551 . 10.1007/s13194-023-00519-8.
2. Web site: Common and Rare Side Effects for misoprostol oral.
3. Web site: Definitions . 2016-04-29 . live . https://web.archive.org/web/20160304222413/http://www.who.int/medicines/areas/quality_safety/safety_efficacy/trainingcourses/definitions.pdf . 2016-03-04.
4. Web site: 2009-09-01. A Guideline on Summary of Product Characteristics. European commission.
5. Mühlbauer V, Mühlhauser I . Understanding adverse drug reactions in package leaflets - an exploratory survey among health care professionals . BMC Health Services Research . 15 . 1 . 505 . November 2015 . 26554666 . 4641349 . 10.1186/s12913-015-1160-1 . free .
6. Mühlbauer V, Prinz R, Mühlhauser I, Wegwarth O . Alternative package leaflets improve people's understanding of drug side effects-A randomized controlled exploratory survey . PLOS ONE . 13 . 9 . e0203800 . 2018-09-13 . 30212555 . 6136776 . 10.1371/journal.pone.0203800 . 2018PLoSO..1303800M . free .
7. News: Drugs firm blocks cheap blindness cure . The Guardian . London . Boseley S . 17 June 2006 . 2010-05-20.
8. Web site: Gracer R . The Buprenorphine Effect on Depression . naabt.org . National Alliance of Advocates for Buprenorphine Treatment . February 2007 . 19 September 2015.
9. Bodkin JA, Zornberg GL, Lukas SE, Cole JO . Buprenorphine treatment of refractory depression . Journal of Clinical Psychopharmacology . 15 . 1 . 49–57 . February 1995 . 7714228 . 10.1097/00004714-199502000-00008 .
10. Web site: Leehey K . Mood Stabilizers for Bipolar Disorder (Manic Depressive) . https://web.archive.org/web/20111113183807/http://www.leeheymd.com/charts/dep4_1.html . 13 November 2011 . Leeheymd.com . 1 August 2003 . 17 August 2011 .
11. Wing DA, Powers B, Hickok D . U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States . Obstetrics and Gynecology . 115 . 4 . 825–833 . April 2010 . 20308845 . 10.1097/AOG.0b013e3181d53843 .
12. Shen WW, Mahadevan J, Hofstatter L, Sata LS . Doxepin as a potent H2 and H2 antihistamine for epigastric distress . The American Journal of Psychiatry . 140 . 7 . 957–8 . July 1983 . 6859336 . 10.1176/ajp.140.7.957 . live . http://archive.wikiwix.com/cache/20110904040738/http://ajp.psychiatryonline.org/cgi/reprint/140/7/957 . 2011-09-04 .
13. Web site: Off-label Use of Gabapentin . https://web.archive.org/web/20070809235342/http://idahodur.isu.edu/leaflets/2004/GABAPENTIN%20EDU%20LEAFLET%202004.pdf . 9 August 2007 . Idaho Drug Utilization Review, educational leaflet. 2004 .
14. Web site: https://web.archive.org/web/20081011183525/http://drugs.nmihi.com/whd/pregnancy.html . Pregnancy . 11 October 2008 . drugs.nmihi.com . (New Medical Information and Health Information).
15. Web site: Deem SG . Premature Ejaculation . Emedicine.com . 2011-08-17 . live . https://web.archive.org/web/20081201091923/http://www.emedicine.com/med/topic643.htm . 2008-12-01.
16. Practice guideline for the treatment of patients with major depressive disorder. 3 . Gelenberg AJ, Freeman MP, Markowitz JC, Rosenbaum JF, Thase ME, Trivedi MH, Silbersweig DA . Am J Psychiatry . 2010 . 167 . Suppl 10 . 9–118.
17. Cheshire WP, Fealey RD . Drug-induced hyperhidrosis and hypohidrosis: incidence, prevention and management . Drug Safety . 31 . 2 . 109–26 . 2008 . 18217788 . 10.2165/00002018-200831020-00002 . 23041000 .
18. Web site: Echinacea - side effects . Drugs.com . 28 June 2023 . 3 April 2023.
19. Wells RE, Turner DP, Lee M, Bishop L, Strauss L . Managing Migraine During Pregnancy and Lactation . Current Neurology and Neuroscience Reports . 16 . 4 . 40 . April 2016 . 27002079 . 10.1007/s11910-016-0634-9 . 10098257 .