Adverse effect (medicine)

In medicine, an Adverse effect is an abnormal, harmful, undesired and/or unintended side-effect, although not necessarily unexpected, which is obtained as a result of a therapyor other medical intervention, such as drug/chemotherapy, physical therapy, surgery, medical procedure, use of a medical device, etc. Iatrogenesis(literally, generated by a physician) is a common cause of adverse effects, as well as medical error. Using a drug or other medical intervention which is contraindicatedmay increase the riskof adverse effects. Adverse effects may cause medical complicationsof a disease or procedure and negatively affect its prognosis.

The harmful outcome is usually indicated by some result such as morbidity, mortality, alteration in body weight, levels of enzymes, loss of function or as a pathologicalchange detected at the microscopic, macroscopic or physiological level. They may cause a reversible or irreversible change, including an increase or decrease in the susceptibility of the individual to other chemicals, foods, or procedures (e.g. drug interaction).

Reporting systems

In many countries, adverse effects are required by law to be reported, researched in clinical trialsand included into the patient information accompanying medical devices and drugs for sale to the public.

USA

In the USAseveral reporting systems have been built, such as the Vaccine Adverse Event Reporting System (VAERS), the Manufacturer and User Facility Device Experience Database (MAUDE) and the Special Nutritionals Adverse Event Monitoring System.

Australia

In Australia, adverse effect reporting is administered by the Adverse Drug Reactions Advisory Committee(ADRAC), a subcommittee of the Australian Drug Evaluation Committee(ADEC). Reporting is voluntary, and ADRAC requests health professionals to report all adverse reactions to its current drugs of interest, and serious adverse reactions to any drug. ADRAC publishes the Australian Adverse Drug Reactions Bulletinevery 2 months.

Adverse effects of medical procedures

Surgery, of course, may have a number of undesirable or harmful after effects, such as infection, hemorrhage, inflammation, scarring, loss of function, changes in local blood flow, and so on. They can be reversible or irreversible, and a compromise must be found by the physician and the patient between the beneficial or life-saving consequences of surgery versus its adverse effects. For example, a limb may be lost to amputationin case of untreatable gangrene, but life is saved. Presently, one of the greatest advantages of minimally invasivesurgery, such as laparoscopic surgeryis the reduction of adverse effects.

Other non-surgical physical procedures such as high intensity radiotherapymay cause burnsand alterations in the skin. In general, these therapies try to avoid damage to healthy tissueswhile maximizing the therapeutic effect.

Vaccinationis a medical procedure which is particularly prone to adverse effects, due to the nature of its biological preparation (sometimes using attenuated pathogensand toxins). Common adverse effects may be fever, malaiseand local reactions in the vaccination site, such as eczema vaccinatum, a severe, sometimes fatal complicaitionwhich may result in persons who have eczemaor atopic dermatitis, and, as such, those persons should not be vaccinated, even if the condition is currently not active.

Diagnostic procedures may also have adverse effects, depending much on whether they are invasive, non-invasiveor minimally invasive. For example, allergicreactions to x-ray contrasting material often occur, a colonoscopymay cause the perforation of the intestine wall, etc.

Adverse effects of drugs

Main article: adverse drug reaction

Adverse effects can occur as a collateral or side effect of many interventions, but they are particularly important in pharmacology, due to its wider, and sometimes uncontrollable, use by way of self-medication. Thus, responsible drug usebecomes an important issue here.

Adverse effects, like intended effects of drugs, are a function of dosageor drug levels at the target organs, so they may be avoided or decreased by means of careful and precise pharmacodynamics(the change of drug levels in the organism in function of time after administration).

Adverse effects may also be caused by drug interaction, i.e., when physicians fail to check for all medicaments a patient is taking and prescribe new ones which interact agonistically or antagonistically (potentiate or decrease the intended therapeutic effect). Significant morbidityand mortalityis caused around the world because of this. Drug-drug and food-drug interactions may occur, and even so-called "natural drugs" used in alternative medicinemay have dangerous adverse effects. For example, extracts of St. John's wort(Hypericum perforatum), a phytotherapic used for treating mild depressionare known to cause an increase in the cytochrome P450enzymes responsible for the metabolismand elimination of many drugs, so that patients taking it are likely to experience a reduction in blood levels of drugs that they are taking for other purposes, such as cancerchemotherapeuticdrugs, protease inhibitorsfor HIVand oral contraceptives.

The scientific field of activity associated with drug safetyis increasingly government-regulated and is of major concern for the public as well as to drug manufacturers. The distinction between adverse and non-adverse effects is a major undertaking when a new drug is developed and tested before marketing it. This is done in toxicitystudies to determine the non-adverse effect level (NOAEL). These studies are used to define the dosage to be used in human testing (phase I) as well as to calculate the maximum admissible daily intake. Imperfections in clinical trials, such as insufficient number of patients or short duration, sometimes lead to public healthdisasters such as those of fenfluramine(the so-called fen-phenepisode), thalidomideand, more recently, of cerivastatin(Baycol®, Lipobay®) and rofecoxib(Vioxx®), where drastic adverse effects were observed, like teratogenesis, pulmonary hypertension, stroke, heart disease, neuropathy, etc., and a significant number of deaths, causing the forced or voluntary withdrawalof the drug from the market.

Most drugs have a large list of non-severe or mild adverse effects which do not rule out the interruption of usage. These effects have widely variable incidence, according to individual sensitivity. They comprise nausea, dizziness, diarrhea, malaise, vomit, headache, dermatitis, dry mouth, etc.

Controversies

Sometimes, putative medical adverse effects are regarded as controversial and generate heated discussions in society and lawsuitsagainst drug manufacturers. One example is the current controversy whether autismmay be caused by the MMR vaccine(or by thimerosal, a mercury-based preservative used in some vaccines). No significative link has been found so far, but this has not prevented lawsuits. Another instance is the potential adverse effects of siliconebreast implants, which lead to hundreds of thousands of litigations against manufacturers of gel-based implants, due to allegations of damage to the immune systemwhich have not yet been conclusively proven.

Due to the exceedingly high impact on public health of widely used medications, such as oral contraceptivesand hormone replacement therapy, which may affect millions of users, even marginal probabilities of adverse effects of a severe nature, such as breast cancer, have led to public outcry and changes in medical therapy, although its benefits largely surpassed the statistical risks.

Examples of adverse effects

• Abortion, miscarriageand/or severe vaginalor uterinehemorrhageassociated with misoprostol(Cytotec®), a labor-inducing drug (this is a case where the adverse effect has been used legally and illegally for performing abortions)
• Addictionto many sedativesand analgesicssuch as diazepam, morphine, etc.
• Bleedingof the intestineassociated with aspirintherapy
• Deafnessand kidney failureassociated with gentamicin(an antibiotic)
• Death, following sedationin children using propofol(Diprivan®)
• Dementiaassociated with heart bypass surgery
• Depressionor hepatic injurycaused by interferon
• Diabetescaused by atypical antipsychoticmedications (neuroleptic psychiatricdrugs)
• Diarrheacaused by the use of orlistat(Xenical®)
• Erectile dysfunctionassociated with many drugs, such as antidepressants
• Feverassociated with vaccination(in the past, imperfectly manufactured vaccines, such as BCGand poliomyelitis, have caused the very disease they intended to fight).
• Glaucomaassociated with corticosteroid-based eye drops
• Hair lossand anemiamay be caused by chemotherapyagainst cancer, leukemia, etc.
• Headachefollowing spinal anesthesia
• Hypertensionin ephedrineusers, which prompted FDA to remove the status of dietary supplementof ephedraextracts
• Insomniacaused by stimulants, Ritalin®, Adderall®, etc.
• Lactic acidosisassociated with the use of stavudine(Zerit®, for anti-HIVtherapy) or metformin(for diabetes)
• Melasmaand thrombosisassociated with oral contraceptiveuse
• Rhabdomyolysisassociated with statins(anti-cholesteroldrugs)
• Seizurescaused by withdrawal from benzodiazepine
• Sleepinessor increase in appetitedue to antihistamineuse
• Strokeor heart attackassociated with sildenafil(Viagra®) when used with nitroglycerine
• Suicide, increased tendency associated to the use of fluoxetineand other SSRIantidepressants
• Tardive dyskinesiaassociated with long-term use of metoclopramideand many antipsychoticmedications

See also

• Biosafety
• Contraindication
• Complication (medicine)
• Drug interaction
• Evidence-based medicine
• FDA
• Iatrogenesis
• List of withdrawn drugs
• Medical algorithm
• Medical error
• Medical prescription
• Perioperative mortality
• Responsible drug use
• Toxicology

External links

• Patient Safety Network. An extremely useful site, with a glossary and articles on all kinds of threats to patient safety, including adverse effects, drug reactions, medical error, iatrogenesis, etc.
• ADRD.org- Searchable Database of Adverse Drug Reactions (ADRs)
• Australian Adverse Drug Reactions Bulletin- published bimonthly by ADRAC
• Drugs of ConcernDrugIntel.com site for tortlawyers with up-to-date information on drugs that cause severe adverse effects)
• Medication Errorsa FDA site.
• Medical Product Safety Information. MedWatch, an useful page from FDA, listing safety alerts for drugs, biologics, devices and dietary supplements, recalls, market withdrawals, public health advisories, links to the VAERS and MAUDE databases, etc.)
• Medical Devices SafetyNational Library of Medicine (Medline Plus, useful lists of conventional drug and medical device articles and websites)es:Reacción adversa a medicamento

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It uses material from the http://en.wikipedia.org/wiki/Adverse+effect+%28medicine%29 Wikipedia article Adverse effect (medicine).