In
medicine, an 'adverse effect' is a harmful and undesired effect resulting from a medication or other intervention such as
chemotherapy or
surgery. An adverse effect may be termed a "side-effect" (when judged to be secondary to a main or therapeutic effect) and may result from an unsuitable or incorrect dosage or procedure (which could be due to
medical error). Adverse effects are sometimes referred to as "
iatrogenic" because they are generated by a physician/treatment. Some adverse effects only occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is
contraindicated may increase the
risk of adverse effects. Adverse effects may cause
medical complications of a disease or procedure and negatively affect its
prognosis. They may also lead to
non-compliance with a treatment regimen.
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
pathological change detected at the microscopic, macroscopic or physiological level. It may also be indicated by symptoms reported by a patient. Adverse effects 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 trials and included into the patient information accompanying medical devices and drugs for sale to the public.
UK
The
Yellow Card Scheme is a
UK initiative run by the
Medicines and Healthcare products Regulatory Agency (MHRA) and the
Commission on Human Medicines (CHM) to gather information on adverse effects to medicines. This includes all licensed medicines from medicines issued on prescription to medicines bought over the counter from a supermarket. The Scheme also includes all herbal preparations and unlicensed medicines found in cosmetic treatments. ADRs can be reported by a number of healthcare professionals including doctors, pharmacists and nurses, as well as patients.
For further information see the
Yellow Card Scheme website, or find copies of the Yellow Card in the appedices of a
BNF.
To read reports from the UK Yellow Card Scheme you can
download here.
USA
In the
USA several 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''.
MedWatch is the main reporting center, operated by the
Food and Drug Administration.
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 Bulletin every 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
amputation in case of untreatable
gangrene, but life is saved. Presently, one of the greatest advantages of
minimally invasive surgery, such as
laparoscopic surgery is the reduction of adverse effects.
Other non-surgical physical procedures such as high intensity
radiotherapy may cause
burns and alterations in the
skin. In general, these therapies try to avoid damage to healthy
tissues while maximizing the therapeutic effect.
Vaccination is a medical procedure which is particularly likely to have adverse effects, due to the nature of its biological preparation (sometimes using attenuated
pathogens and
toxins). Common adverse effects may be
fever,
malaise and local reactions in the vaccination site, such as
eczema vaccinatum, a severe, sometimes fatal
complication which may result in persons who have
eczema or 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-invasive or
minimally invasive. For example,
allergic reactions to x-ray contrasting material often occur, a
colonoscopy may cause the perforation of the intestine wall, etc.
Adverse effects of drugs
Main articles: 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 use becomes an important issue here.
Adverse effects, like intended effects of drugs, are a function of
dosage or drug levels at the target organs, so they may be avoided or decreased by means of careful and precise
pharmacokinetics (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
morbidity and mortality is caused around the world because of this. Drug-drug and food-drug interactions may occur, and even so-called "natural drugs" used in
alternative medicine may have dangerous adverse effects. For example, extracts of
St. John's wort (''Hypericum perforatum''), a phytotherapic used for treating mild
depression are known to cause an increase in the
cytochrome P450 enzymes responsible for the
metabolism and 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
cancer chemotherapeutic drugs,
protease inhibitors for
HIV and
hormonal contraceptives.
The scientific field of activity associated with
drug safety is 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
toxicity studies 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 health disasters such as those of
fenfluramine (the so-called
fen-phen episode),
thalidomide and, 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
withdrawal of 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
lawsuits against drug manufacturers. One example is the current controversy whether
autism may be caused by the
MMR vaccine (or by
thimerosal, a
mercury-based preservative used in some
vaccines). No link has been found in any study and no change in the rate of autism has occurred when thimerisal was removed from vaccines a decade ago in Canada.
Another instance is the potential adverse effects of
silicone breast implants, which lead to hundreds of thousands of litigations against manufacturers of gel-based implants, due to allegations of damage to the
immune system which have not yet been conclusively proven.
Due to the exceedingly high impact on public health of widely used medications, such as
hormonal contraception and
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.
Limitations of adverse effects reporting
In principle, medical professionals are required to report all adverse effects related to a specific form of therapy. In practice, it is at the discretion of the professional to determine whether a medical event is at all related to the therapy. For example, a leg
fracture in a skiing accident in a patient who years before took antibiotics for
pneumonia is not likely to get reported.
As a result, routine adverse effects reporting may often not include long-term and subtle effects that may ultimately be attributed to a therapy.
Examples of adverse effects
★
Abortion,
miscarriage or
uterine hemorrhage associated with
misoprostol (
Cytotec®), a labor-inducing drug (this is a case where the adverse effect has been used legally and illegally for performing abortions)
★
Addiction to many
sedatives and
analgesics such as
diazepam,
morphine, etc.
★
Bleeding of the
intestine associated with
aspirin therapy
★
Deafness and
kidney failure associated with
gentamicin (an
antibiotic)
★
Death, following
sedation in children using
propofol (
Diprivan®)
★
Dementia associated with
heart bypass surgery
★
Depression or
hepatic injury caused by
interferon
★
Diabetes caused by
atypical antipsychotic medications (neuroleptic
psychiatric drugs)
★
Diarrhea caused by the use of
orlistat (
Xenical®)
★
Erectile dysfunction associated with many drugs, such as
antidepressants
★
Fever associated with
vaccination (in the past, imperfectly manufactured vaccines, such as
BCG and
poliomyelitis, have caused the very disease they intended to fight).
★
Glaucoma associated with
corticosteroid-based
eye drops
★
Hair loss and
anemia may be caused by
chemotherapy against
cancer,
leukemia, etc.
★
Headache following
spinal anesthesia
★
Hypertension in
ephedrine users, which prompted FDA to remove the status of
dietary supplement of
ephedra extracts
★
Insomnia caused by stimulants,
Ritalin®,
Adderall®, etc.
★
Lactic acidosis associated with the use of
stavudine (Zerit®, for anti-
HIV therapy) or
metformin (for diabetes)
★
Melasma and
thrombosis associated with use of estrogen-containing
hormonal contraception such as the
combined oral contraceptive pill
★
Rhabdomyolysis associated with
statins (anti-
cholesterol drugs)
★
Seizures caused by withdrawal from
benzodiazepine
★
Sleepiness or increase in
appetite due to
antihistamine use
★
Stroke or
heart attack associated with
sildenafil (
Viagra®) when used with
nitroglycerine
★
Suicide, increased tendency associated to the use of
fluoxetine and other
SSRI antidepressants
★
Tardive dyskinesia associated with long-term use of
metoclopramide and many
antipsychotic medications
See also
★
Biosafety
★
Consultant pharmacist
★
Contraindication
★
Complication (medicine)
★
Drug interaction
★
Evidence-based medicine
★
Food and Drug Administration
★
Iatrogenesis
★
List of withdrawn drugs
★
Medical algorithm
★
Medical error
★
Medical prescription
★
Nocebo
★
Patient safety
★
Perioperative mortality
★
Pharmacovigilance
★
Pharmacovigilance
★
EudraVigilance
★
Placebo (origins of technical term)
★
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.
★
Australian Adverse Drug Reactions Bulletin - published bimonthly by ADRAC
★
Drugs of Concern DrugIntel.com site for
tort lawyers with up-to-date information on drugs that cause severe adverse effects)
★
Medication Errors a FDA site.
★
Medical Product Safety Information. MedWatch, an useful page from
Food and Drug Administration, 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 Safety National Library of Medicine (Medline Plus, useful lists of conventional drug and medical device articles and websites)
★
When Medicine Hurts Instead of Helps - A special report by the
Alliance for Aging Research on ADRs.
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