Febrifuge
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An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
. Antipyretics cause the
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
to override a prostaglandin-induced increase in
temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer. Thermometers are calibrated in various Conversion of units of temperature, temp ...
. The body then works to lower the temperature, which results in a reduction in fever. Most antipyretic medications have other purposes. The most common antipyretics in the US are usually ibuprofen and
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
, which are
nonsteroidal anti-inflammatory drugs Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
(NSAIDs) used primarily as anti-inflammatories and
analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
(pain relievers), but which also have antipyretic properties; and paracetamol (acetaminophen), an analgesic without anti-inflammatory properties. There is some debate over the appropriate use of such medications, since fever is part of the body's
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
to infection. A study published by the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
claims that fever suppression causes at least 1% more influenza deaths in the United States, or 700 extra deaths per year.


Non-pharmacological treatment

Bathing or sponging with lukewarm or cool water can effectively reduce body temperature in those with
heat illness Heat illness is a spectrum of disorders due to increased body temperature. It can be caused by either environmental conditions or by exertion. It includes minor conditions such as heat cramps, heat syncope, and heat exhaustion as well as the mo ...
, but not usually in those with fever. The use of alcohol baths is not an appropriate cooling method, because there have been reported adverse events associated with systemic absorption of alcohol.


Medications

The list of medications with antipyretic effects includes many common drugs that also have analgesic and anti-inflammatory activity, several of which are commonly sold
over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
(OTC). * NSAIDs (non-steroidal anti-inflammatory drugs), a broad class of medications that in addition to their defining effect of reducing inflammation, also tend to be potent analgesics and antipyretics. The majority work by inhibiting the activity of the
cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as pr ...
(COX) family of enzymes in the body. ** Nonselective COX enzyme inhibitors like ibuprofen and
naproxen Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulat ...
. **
Salicylate Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substance ...
s, including
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
(acetylsalicylic acid),
magnesium salicylate Magnesium salicylate is a common analgesic and nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate musculoskeletal pain such as in tendons and muscles. It is also used to treat joint pain like arthritis, general back pai ...
, and
sodium salicylate Sodium salicylate is a sodium salt of salicylic acid. It can be prepared from sodium phenolate and carbon dioxide under higher temperature and pressure. Historically, it has been synthesized by refluxing methyl salicylate (wintergreen oil) with a ...
. These are also primarily nonselective COX inhibitors, but also work through other mechanisms including activating
AMP-activated protein kinase 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cell ...
. ** COX inhibitors that are relatively selective for the
COX-1 Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of two cyclooxygenases. ...
enzyme, such as
ketoprofen Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin. It was patented in 1967 and approved for medica ...
and
flurbiprofen Flurbiprofen is a member of the phenylalkanoic acid derivative family of nonsteroidal anti-inflammatory drugs (NSAIDs). It is primarily indicated as a pre-operative anti-miotic (in an ophthalmic solution) as well as orally for arthritis or de ...
. ** Conversely, COX inhibitors that are relatively selective for
COX-2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
, including
nimesulide Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) with pain medication and fever reducing properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis, and primary dysmenorrhoea in ...
,
diclofenac Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or ...
and
celecoxib Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankyl ...
. **
Phenazone Phenazone (INN and BAN; also known as phenazon, antipyrine (USAN), or analgesine) is an analgesic (pain reducing), antipyretic (fever reducing) and anti-inflammatory drug. While it predates the term, it is often classified as a nonsteroidal anti- ...
-like drugs (
pyrazolone Pyrazolone is 5-membered heterocycle containing two adjacent nitrogen atoms. It can be viewed as a derivative of pyrazole possessing an additional carbonyl (C=O) group. Compounds containing this functional group are useful commercially in analgesic ...
s), many of which have been largely phased out of used owing to safety concerns in most countries (including metamizole, banned in over 30 countries for causing agranulocytosis), but remain available in some locations or for specific purposes such as for treating
otitis media Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...
in the form of
ear drops Ear drops are a form of topical medication for the ears used to treat infection, inflammation, impacted ear wax and local anesthesia. They are commonly used for short-term treatment and can be purchased with or without a prescription. Before u ...
. * Paracetamol (acetaminophen) class antipyretics, which have negligible anti-inflammatory activity. Apart from paracetamol itself, the medications in this class are mainly previously marketed drugs which were withdrawn owing to safety concerns, one example of this being phenacetin. * A few other medications have antipyretic effects of varying strength. While these medications tend to have too weak fever reducing effects or too many adverse effects to use primarily as antipyretics, their antipyretic effect may occasionally be useful. For example, there are theoretical reasons to believe, as well as slight evidence from one human trial, that α2-adrenergic agonists, and particularly clonidine (a common drug used to treat high blood pressure, ADHD,
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...
and several other conditions), may have antipyretic effects, which if verified could potentially be useful in patients with septic shock or acute respiratory distress syndrome.


Use in children

The U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) notes that improper dosing is one of the biggest problems in giving acetaminophen (paracetamol) to children. The effectiveness of acetaminophen alone as an antipyretic in children is uncertain, with some evidence showing it is no better than physical methods. Therapies involving alternating doses of acetaminophen and ibuprofen have shown greater antipyretic effect than either drug alone. One meta-analysis indicated that ibuprofen is more effective than acetaminophen in children at similar doses when both are given alone. Due to concerns about
Reye syndrome Reye syndrome is a rapidly worsening brain disease. Symptoms of Reye syndrome may include vomiting, personality changes, confusion, seizures, and loss of consciousness. While liver toxicity typically occurs in the syndrome, jaundice usuall ...
, it is recommended that aspirin and combination products that contain aspirin not be given to children or teenagers during episodes of fever-causing illnesses.


Traditional medicine

Traditional use of
vascular plant Vascular plants (), also called tracheophytes () or collectively Tracheophyta (), form a large group of land plants ( accepted known species) that have lignified tissues (the xylem) for conducting water and minerals throughout the plant. They ...
s with antipyretic properties is a common worldwide feature of many
ethnobotanical Ethnobotany is the study of a region's plants and their practical uses through the traditional knowledge of a local culture and people. An ethnobotanist thus strives to document the local customs involving the practical uses of local flora for m ...
cultures. In ethnobotany, a plant with naturally occurring antipyretic properties is commonly referred to as a ''febrifuge''.


References

{{Wiktionary