HOME

TheInfoList



OR:

Ibuprofen is a
nonsteroidal anti-inflammatory drug 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 ...
(NSAID) that is used for treating
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
,
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, and
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
. This includes painful menstrual periods,
migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
s, and
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
. It may also be used to close a
patent ductus arteriosus ''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...
in a
premature baby Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 2 ...
. It can be used by mouth or
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
. It typically begins working within an hour. Common side effects include
heartburn Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the ma ...
and a
rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
. Compared to other NSAIDs, it may have other side effects such as
gastrointestinal bleeding Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may incl ...
. It increases the risk of
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, and liver failure. At low doses, it does not appear to increase the risk of
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
; however, at higher doses it may. Ibuprofen can also worsen
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
. While whether it is safe in early
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
is unclear, it appears to be harmful in later pregnancy, so is not recommended. Like other NSAIDs, it works by inhibiting the production of
prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
by decreasing the activity of the enzyme
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 prosta ...
(COX). Ibuprofen is a weaker anti-inflammatory agent than other NSAIDs. Ibuprofen was discovered in 1961 by Stewart Adams and John Nicholson while working at
Boots UK Limited Boots UK Limited (formerly Boots the Chemists), trading as Boots, is a British health and beauty retailer and pharmacy chain in the United Kingdom and other countries and territories including Ireland, Italy, Norway, the Netherlands, Thailand an ...
and initially marketed as Brufen. It is available under a number of
trade names A trade name, trading name, or business name, is a pseudonym used by companies that do not operate under their registered company name. The term for this type of alternative name is a "fictitious" business name. Registering the fictitious name w ...
, including
Nurofen Nurofen is a brand name range of pain-relief medication containing ibuprofen made by the British multinational Reckitt. Introduced in 1983, the Nurofen brand was acquired following Reckitt Benckiser's acquisition of Boots in 2005. The brand is ...
, Advil, and Motrin. Ibuprofen was first marketed in 1969 in the United Kingdom and in 1974 in the United States. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. It is available as a
generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. In 2020, it was the 38th-most commonly prescribed medication in the United States, with more than 16million prescriptions.


Medical uses

Ibuprofen is used primarily to treat
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
(including postvaccination fever), mild to moderate
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
(including pain relief after
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
),
painful menstruation Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...
,
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
, dental pain,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
s, and pain from kidney stones. About 60% of people respond to any NSAID; those who do not respond well to a particular one may respond to another. It is used for inflammatory diseases such as
juvenile idiopathic arthritis Juvenile idiopathic arthritis (JIA) is the most common, chronic rheumatic disease of childhood, affecting approximately one per 1,000 children. ''Juvenile'', in this context, refers to disease onset before 16 years of age, while ''idiopathic'' r ...
and
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
. It is also used for
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
and
patent ductus arteriosus ''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...
.


Lysine

In some countries, ibuprofen
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
(the lysine salt of ibuprofen, sometimes called "ibuprofen lysinate") is licensed for treatment of the same conditions as ibuprofen; the lysine salt is used because it is more water-soluble. Ibuprofen lysine is sold for rapid pain relief; given in form of a lysine salt, absorption is much quicker (35 minutes compared to 90120 minutes). However, a clinical trial with 351 participants in 2020, funded by Sanofi, found no significant difference between ibuprofen and ibuprofen lysine concerning the eventual onset of action or analgesic efficacy. In 2006, ibuprofen lysine was approved in the U.S. by the
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) for closure of patent ductus arteriosus in premature infants weighing between , who are no more than 32 weeks' gestational age when usual medical management (such as fluid restriction, diuretics, and respiratory support) is not effective.


Adverse effects

Adverse effects include
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...
,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, gastrointestinal ulceration/bleeding,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...
, rash, salt and fluid retention, and
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
. Infrequent adverse effects include esophageal ulceration,
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, high blood levels of potassium, kidney impairment, confusion, and
bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...
. Ibuprofen can exacerbate asthma, sometimes fatally. Allergic reactions, including anaphylaxis and anaphylactic shock, may occur. Ibuprofen may be quantified in blood, plasma, or serum to demonstrate the presence of the drug in a person having experienced an anaphylactic reaction, confirm a diagnosis of poisoning in people who are hospitalized, or assist in a medicolegal death investigation. A
monograph A monograph is a specialist work of writing (in contrast to reference works) or exhibition on a single subject or an aspect of a subject, often by a single author or artist, and usually on a scholarly subject. In library cataloging, ''monograph ...
relating ibuprofen plasma concentration, time since ingestion, and risk of developing renal toxicity in people who have overdosed has been published. In October 2020, the US FDA required the drug label to be updated for all NSAID medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.


Cardiovascular risk

Along with several other NSAIDs, chronic ibuprofen use has been found correlated with risk of progression to
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
in women, though less than for acetaminophen, and
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
(heart attack), particularly among those chronically using higher doses. On 9 July 2015, the US FDA toughened warnings of increased
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
and
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
risk associated with ibuprofen and related NSAIDs; the NSAID
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 ...
is not included in this warning. The
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) issued similar warnings in 2015.


Skin

Along with other NSAIDs, ibuprofen has been associated with the onset of
bullous pemphigoid Bullous pemphigoid (type of pemphigoid) is an autoimmune pruritic skin disease which typically occurs in people aged over 60, that may involve the formation of blisters ( bullae) in the space between the epidermal and dermal skin layers. It is cla ...
or pemphigoid-like blistering. As with other NSAIDs, ibuprofen has been reported to be a photosensitising agent, but it is considered a weak photosensitising agent compared to other members of the 2-arylpropionic acid class. Like other NSAIDs, ibuprofen is an extremely rare cause of the
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...
(SJS). Ibuprofen is also an extremely rare cause of
toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...
.


Interactions


Alcohol

Drinking alcohol when taking ibuprofen may increase the risk of
stomach bleeding Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit or in altered form as black stool. De ...
.


Aspirin

According to the FDA, "ibuprofen can interfere with the
antiplatelet An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...
effect of low-dose
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 ...
, potentially rendering aspirin less effective when used for cardioprotection and
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
prevention". Allowing sufficient time between doses of ibuprofen and immediate-release (IR) aspirin can avoid this problem. The recommended elapsed time between a dose of ibuprofen and a dose of aspirin depends on which is taken first. It would be 30 minutes or more for ibuprofen taken after IR aspirin, and 8 hours or more for ibuprofen taken before IR aspirin. However, this timing cannot be recommended for enteric-coated aspirin. If ibuprofen is taken only occasionally without the recommended timing, though, the reduction of the cardioprotection and stroke prevention of a daily aspirin regimen is minimal. *


Paracetamol

Ibuprofen combined with
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
is considered generally safe in children for short-term usage.


Overdose

Ibuprofen overdose has become common since it was licensed for OTC use. Many overdose experiences are reported in the
medical literature Medical literature is the scientific literature of medicine: articles in journals and texts in books devoted to the field of medicine. Many references to the medical literature include the health care literature generally, including that of denti ...
, although the frequency of life-threatening complications from ibuprofen overdose is low. Human responses in cases of overdose range from an absence of symptoms to a fatal outcome despite intensive-care treatment. Most symptoms are an excess of the pharmacological action of ibuprofen, and include abdominal pain, nausea,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...
, drowsiness, dizziness, headache, ear ringing, and
nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...
. Rarely, more severe symptoms, such as
gastrointestinal bleeding Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may incl ...
,
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
,
metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
, hyperkalemia,
low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
,
slow heart rate Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
,
fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, atrial fibrillation,
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, liver dysfunction,
acute kidney failure Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...
,
cyanosis Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
,
respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
, and
cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
have been reported. The severity of symptoms varies with the ingested dose and the time elapsed; however, individual sensitivity also plays an important role. Generally, the symptoms observed with an overdose of ibuprofen are similar to the symptoms caused by overdoses of other NSAIDs. Correlation between severity of symptoms and measured ibuprofen plasma levels is weak. Toxic effects are unlikely at doses below 100mg/kg, but can be severe above 400mg/kg (around 150 tablets of 200mg units for an average man); however, large doses do not indicate the clinical course is likely to be lethal. A precise
lethal dose In toxicology, the lethal dose (LD) is an indication of the lethal toxicity of a given substance or type of radiation. Because resistance varies from one individual to another, the "lethal dose" represents a dose (usually recorded as dose per kilog ...
is difficult to determine, as it may vary with age, weight, and concomitant conditions of the individual person. Treatment to address an ibuprofen overdose is based on how the symptoms present. In cases presenting early, decontamination of the stomach is recommended. This is achieved using
activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an interv ...
; charcoal adsorbs the drug before it can enter the
bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
.
Gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...
is now rarely used, but can be considered if the amount ingested is potentially life-threatening, and it can be performed within 60 minutes of ingestion. Purposeful vomiting is not recommended. Most ibuprofen ingestions produce only mild effects, and the management of overdose is straightforward. Standard measures to maintain normal urine output should be instituted and
kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...
monitored. Since ibuprofen has acidic properties and is also excreted in the urine, forced alkaline diuresis is theoretically beneficial. However, because ibuprofen is highly protein-bound in the blood, the kidneys' excretion of unchanged drug is minimal. Forced alkaline diuresis is, therefore, of limited benefit.


Miscarriage

A Canadian study of pregnant women suggests that those taking any type or amount of NSAIDs (including ibuprofen,
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
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 formulati ...
) were 2.4 times more likely to
miscarry Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is fetal viability, able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE a ...
than those not taking the medications. However, an Israeli study found no increased risk of miscarriage in the group of mothers using NSAIDs.


Pharmacology

NSAIDs such as ibuprofen work by inhibiting 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 prosta ...
(COX) enzymes, which convert
arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
to prostaglandin H2 (PGH2). PGH2, in turn, is converted by other enzymes to several other
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s (which are mediators of pain,
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, and fever) and to thromboxane A2 (which stimulates
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
aggregation, leading to the formation of
blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
). Like aspirin and
indomethacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription drug, prescription medication to reduce fever, pain, joint stiffness, stiffness, and swelling (medical), swelling from infl ...
, ibuprofen is a nonselective COX inhibitor, in that it inhibits two
isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of cyclooxygenase,
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. ...
and
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. ...
. The
analgesic 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 ...
,
antipyretic An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...
, and anti-inflammatory activity of NSAIDs appears to operate mainly through inhibition of COX-2, which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 instead would be responsible for unwanted effects on the gastrointestinal tract. However, the role of the individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of NSAIDs is uncertain, and different compounds cause different degrees of analgesia and gastric damage. Ibuprofen is administered as a
racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
. The ''R''-enantiomer undergoes extensive interconversion to the ''S''-enantiomer ''in vivo''. The ''S''-enantiomer is believed to be the more pharmacologically active enantiomer. The ''R''-enantiomer is converted through a series of three main enzymes. These enzymes include acyl-CoA-synthetase, which converts the ''R''-enantiomer to (−)-''R''-ibuprofen I-CoA; 2-arylpropionyl-CoA epimerase, which converts (−)-''R''-ibuprofen I-CoA to (+)-''S''-ibuprofen I-CoA; and hydrolase, which converts (+)-''S''-ibuprofen I-CoA to the ''S''-enantiomer. In addition to the conversion of ibuprofen to the ''S''-enantiomer, the body can metabolize ibuprofen to several other compounds, including numerous hydroxyl, carboxyl and glucuronyl metabolites. Virtually all of these have no pharmacological effects. Unlike most other NSAIDs, ibuprofen also acts as an inhibitor of
Rho kinase Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton. ROCKs ( ...
and may be useful in recovery from spinal-cord injury.


Pharmacokinetics

After oral administration, peak serum concentration is reached after 12 hours, and up to 99% of the drug is bound to plasma proteins. The majority of ibuprofen is metabolized and eliminated within 24 hours in the urine; however, 1% of the unchanged drug is removed through biliary excretion.


Chemistry

Ibuprofen is practically insoluble in water, but very soluble in most organic solvents like
ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
(66.18g/100mL at 40°C for 90% EtOH),
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
,
acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...
and
dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...
. The original synthesis of ibuprofen by the Boots Group started with the compound 2-methylpropylbenzene. The synthesis took six steps. A modern, greener technique for the synthesis involves only three steps.


Stereochemistry

Ibuprofen, like other 2-arylpropionate derivatives 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 ...
,
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 dent ...
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 formulati ...
, contains a
stereocenter In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...
in the α-position of the
propionate Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liqu ...
moiety. The product sold in pharmacies is a
racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
of the ''S'' and ''R''-isomers. The ''S'' (dextrorotatory) isomer is the more biologically active; this isomer has been isolated and used medically (see
dexibuprofen Dexibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It is the active dextrorotatory enantiomer of ibuprofen. Most ibuprofen formulations contain a racemic mixture of both isomers. Chemistry Basically Dexibuprofen is a chiral ...
for details). The
isomerase Isomerases are a general class of enzymes that convert a molecule from one isomer to another. Isomerases facilitate intramolecular rearrangements in which bonds are broken and formed. The general form of such a reaction is as follows: A–B ...
enzyme,
alpha-methylacyl-CoA racemase α-Methylacyl-CoA racemase (AMACR, ) is an enzyme that in humans is encoded by the ''AMACR'' gene. AMACR catalyzes the following chemical reaction: :(2''R'')-2-methylacyl-CoA \rightleftharpoons (2''S'')-2-methylacyl-CoA In mammalian cells, the ...
, converts (''R'')-ibuprofen into the (''S'')-
enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
. The (S)- ibuprofen, the
eutomer The eudysmic ratio (also spelled eudismic ratio) represents the difference in pharmacologic activity between the two enantiomers of a drug. In most cases where a chiral compound is biologically active, one enantiomer is more active than the other ...
, harbors the desired therapeutic activity. Interestingly, the inactive (R)-enantiomer, the
distomer The eudysmic ratio (also spelled eudismic ratio) represents the difference in pharmacologic activity between the two enantiomers of a drug. In most cases where a chiral compound is biologically active, one enantiomer is more active than the other ...
, undergoes a unidirectional
chiral inversion Chiral inversion is the process of conversion of one enantiomer of a chiral molecule to its mirror-image version with no other change in the molecule. Chiral inversion happens depending on various factors (viz. biological-, solvent-, light-, temper ...
to offer the active (S)-enantiomer. That is, when the ibuprofen is administered as a racemate the distomer is converted ''in vivo'' into the eutomer while the latter is unaffected.


History

Ibuprofen was derived from
propionic acid Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liq ...
by the
research Research is "creativity, creative and systematic work undertaken to increase the stock of knowledge". It involves the collection, organization and analysis of evidence to increase understanding of a topic, characterized by a particular att ...
arm of
Boots Group Boots UK Limited (formerly Boots the Chemists), trading as Boots, is a British health and beauty retailer and pharmacy chain in the United Kingdom and other countries and territories including Ireland, Italy, Norway, the Netherlands, Thailand an ...
during the 1960s. The name is derived from the 3 functional groups: isobutyl (ibu) propionic acid (pro) phenyl (fen). Its discovery was the result of research during the 1950s and 1960s to find a safer alternative to
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 ...
. The molecule was discovered and synthesized by a team led by Stewart Adams, with a patent application filed in 1961. Adams initially tested the drug as treatment for his
hangover A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical sympto ...
. In 1985, Boots' worldwide patent for ibuprofen expired and generic products were launched. The drug was launched as a treatment for
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
in the United Kingdom in 1969, and in the United States in 1974. Later, in 1983 and 1984, it became the first NSAID (other than aspirin) to be available
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) in these two countries. Boots was awarded the Queen's Award for Technical Achievement in 1985 for the development of the drug. Dr. Adams was subsequently awarded an
Order of the British Empire The Most Excellent Order of the British Empire is a British order of chivalry, rewarding contributions to the arts and sciences, work with charitable and welfare organisations, and public service outside the civil service. It was established ...
(OBE) in 1987. In November 2013, work on ibuprofen was recognized by the erection of a Royal Society of Chemistry blue plaque at Boots' Beeston Factory site in Nottingham, which reads: and another at
BioCity Nottingham BioCity Nottingham is a bioscience science park in central Nottingham in the United Kingdom. It is the UK's largest bioscience innovation and incubation centre. History In 2002, laboratories and office space were donated to Nottingham Trent Un ...
, the site of the original laboratory, which reads:


Society and culture


Availability

Ibuprofen was made available under prescription in the United Kingdom in 1969, and in the United States in 1974. In the years since, the good tolerability profile, along with extensive experience in the population, as well as in so-called phase-IV trials (postapproval studies), have resulted in the availability of ibuprofen OTC in pharmacies worldwide, as well as in supermarkets and other general retailers. Ibuprofen is its International nonproprietary name (INN),
British Approved Name A British Approved Name (BAN) is the official, non-proprietary, or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). The BAN is also the official name used in some countries around the world, because ...
(BAN),
Australian Approved Name An Australian Approved Name (AAN) is a generic drug name set by the Therapeutic Goods Administration (TGA) for use in Australia. In late 2016, the TGA changed several drug names to the corresponding international nonproprietary name (INN), or, in ...
(AAN) and
United States Adopted Name A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Stat ...
(USAN). In the U.S., Motrin has been on the market since 1974, and Advil has been on the market since 1984. Ibuprofen is commonly available in the United States up to the FDA's 1984 dose limit OTC, rarely used higher by prescription. In 2009, the first injectable formulation of ibuprofen was approved in the United States, under the trade name Caldolor.


Route

It can be used by mouth, as a tablet, capsule or suspension, or
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
.


Research

Ibuprofen is sometimes used for the treatment of acne because of its
anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
properties, and has been sold in Japan in topical form for adult acne. As with other NSAIDs, ibuprofen may be useful in the treatment of severe
orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
(low blood pressure when standing up). NSAIDs are of unclear utility in the prevention and treatment of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. Ibuprofen has been associated with a lower risk of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and may delay or prevent it.
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 ...
, other NSAIDs, and
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(acetaminophen) had no effect on the risk for Parkinson's. In March 2011, researchers at
Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
announced in ''
Neurology Neurology (from el, wikt:νεῦρον, νεῦρον (neûron), "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine), medicine dealing with the diagnosis and treatment of all categories of co ...
'' that ibuprofen had a
neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
effect against the risk of developing
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. People regularly consuming ibuprofen were reported to have a 38% lower risk of developing Parkinson's disease, but no such effect was found for other pain relievers, such as aspirin and paracetamol. Use of ibuprofen to lower the risk of Parkinson's disease in the general population would not be problem-free, given the possibility of adverse effects on the urinary and digestive systems. Some
dietary supplements A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients either extr ...
might be dangerous to take along with ibuprofen and other NSAIDs, but more research needs to be conducted to be certain. These supplements include those that can prevent platelet aggregation, including
ginkgo ''Ginkgo'' is a genus of non-flowering seed plants. The scientific name is also used as the English name. The order to which it belongs, Ginkgoales, first appeared in the Permian, 270 million years ago, and is now the only living genus within ...
,
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
,
ginger Ginger (''Zingiber officinale'') is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices ...
,
bilberry Bilberries (), or sometimes European blueberries, are a primarily Eurasian species of low-growing shrubs in the genus ''Vaccinium'' (family Ericaceae), bearing edible, dark blue berries. The species most often referred to is ''Vaccinium myrtillus ...
,
dong quai ''Angelica sinensis'', commonly known as ''dong quai'' () or female ginseng, is a herb belonging to the family Apiaceae, indigenous to China. ''Angelica sinensis'' grows in cool high altitude mountains in East Asia. The yellowish brown root of th ...
,
feverfew ''Tanacetum parthenium'', known as feverfew, is a flowering plant in the daisy family, Asteraceae. It may be grown as an ornamental plant, ornament, and may be identified by its synonyms, ''Chrysanthemum parthenium'' and ''Pyrethrum parthenium' ...
,
ginseng Ginseng () is the root of plants in the genus ''Panax'', such as Korean ginseng ('' P. ginseng''), South China ginseng ('' P. notoginseng''), and American ginseng ('' P. quinquefolius''), typically characterized by the presence of ginsenosides an ...
,
turmeric Turmeric () is a flowering plant, ''Curcuma longa'' (), of the ginger family, Zingiberaceae, the rhizomes of which are used in cooking. The plant is a perennial, rhizomatous, herbaceous plant native to the Indian subcontinent and Southeast Asi ...
, meadowsweet (''Filipendula ulmaria''), and
willow Willows, also called sallows and osiers, from the genus ''Salix'', comprise around 400 speciesMabberley, D.J. 1997. The Plant Book, Cambridge University Press #2: Cambridge. of typically deciduous trees and shrubs, found primarily on moist s ...
(''Salix'' spp.); those that contain
coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by a lactone-like chain , forming a second six-membered h ...
, including
chamomile Chamomile (American English) or camomile (British English; see spelling differences) ( or ) is the common name for several plants of the family Asteraceae. Two of the species, ''Matricaria recutita'' and ''Anthemis nobilis'', are commonly us ...
,
horse chestnut The genus ''Aesculus'' ( or ), with species called buckeye and horse chestnut, comprises 13–19 species of flowering plants in the family Sapindaceae. They are trees and shrubs native to the temperate Northern Hemisphere, with six species n ...
,
fenugreek Fenugreek (; ''Trigonella foenum-graecum'') is an annual plant in the family Fabaceae, with leaves consisting of three small obovate to oblong leaflets. It is cultivated worldwide as a semiarid crop. Its seeds and leaves are common ingredients ...
and
red clover ''Trifolium pratense'', the red clover, is a herbaceous species of flowering plant in the bean family Fabaceae, native to Europe, Western Asia, and northwest Africa, but planted and naturalized in many other regions. Description Red clov ...
; and those that increase the risk of bleeding, like
tamarind Tamarind (''Tamarindus indica'') is a Legume, leguminous tree bearing edible fruit that is probably indigenous to tropical Africa. The genus ''Tamarindus'' is monotypic taxon, monotypic, meaning that it contains only this species. It belongs ...
.


References


External links

* * * {{Authority control Analgesics British inventions Haleon Hepatotoxins Nephrotoxins Nonsteroidal anti-inflammatory drugs Propionic acids Racemic mixtures World Health Organization essential medicines Wikipedia medicine articles ready to translate