Structure And Properties Of Ibuprofen

Structure And Properties Of isobutylphenyl propionic acid isobutylphenyl propionic acid, which is a member of the propionic acid group of Non-steroidal anti-inflammatory, drugs (NSAIDs). ibuprofen is a racemic mixture of +S- and -R-enantiomers. ibuprofen contains contains a stereocenter in the -position of thepropionatemoiety. Studies shown that +S - isobutylphenyl propionic acid was the active form and it showed activity in both in-vivo and in-vitro.ibuprofen is white to off-white in colour and occurs as a crystalline powder, with a break up point of 74 to 77C. It is practically insoluble in water, but readily soluble in organic solvents such as ethanol and acetone. Ibuprofen has a pKa value of 4.430.03 and an n-octanol/water partition coefficient of 11.7 at pH 7.4. The chemical name for isobutylphenyl propionic acid is ()-2-(p-iso-butylphenyl) propionic acid. The molecular weight of ibuprofen is 206.28. Its molecular formula is C13H1802. appliance of actionThe major action of Ib uprofen and all new(prenominal) Non-steroidal anti-inflammatory drugs and is the inhibition of the cyclooxygenase enzyme or the COX enzymes and hence inhibiting the synthesis of prostaglandins. These cyclooxygenase enzymes catalyze the reaction of synthesis of prostaglandins and thromboxanes from arachidonic acid, which in turn is synthesized from phospholipids by the action of the phospholipase enzyme. The prostaglandins and thromboxanes atomic number 18 then responsible for the synthesis of various inflammatory mediators. there are two types of cyclooxygenase enzymes namely, cyclooxygenase enzyme-I (COX-I) and cyclooxygenase enzyme-II (COX-II). COX-I is a constitutive enzyme which is released in most of the body tissues including the blood platelets. COX-I performs a house-keeping role in the body and is involved in the tissue homeostasis. Whereas, COX-II is present in the inflammatory cells and is responsible for the production of prostanoid mediators, which are responsible for inflammation, pain and fever. Therefore, inhibition of the COX-II leads to the anti-inflammatory, anti-pyretic and analgesic activity of ibuprofen and whereas on the other hand, inhibition of COX-II is responsible for the unwanted effects of ibuprofen in the gastric mucosa and on platelet aggregation.In 2002, a study inform that, ibuprofen selectively inhibits a new variantof theCOX enzyme that was totally differentfrom thethen known two variants of cyclooxygenase enzymes, the COX-I andCOX-II. This iso-enzyme is now referred as the COX-III enzyme. Study in like manner showed that this COX-III enzyme was only expressed in thebrain andin thespinal cord. Its exactmechanismand actions is still poorly understood, but future researchmay submitfurther insight into how it works. A study on rats has shown that administration of ibuprofen increases thebioavailability of serotonin (5-HT) in rats and evidence for a similar mechanismin public was besides found. Chronic ibuprofen doses in rat showed down-regulation of central 5-HT2A receptors andan increasein thenumber of serotonin transporter proteins.In 2006, a study showed that ibuprofen is converted to N-arachidonoyl phenolamine, or AM404, a compound known as an endogenous cannabinoid reuptake inhibitor and it indirectly activates theCB-I cannabinoid receptor, military issueingin analgesia. This activity was proven through theinduction of a CB-I receptor antagonistwhichresulted in thereversal of theanalgesic actionof ibuprofen.PharmacokineticsAbsorptionIbuprofen is well absorbed from the gastro intestinal tract. The peak plasma level of ibuprofen is reached within 1 to 2 hours. It was shown in a study that absorption of ibuprofen is faster in fasting conditions. Food affects the rate of absorption of ibuprofen but the extent of absorption remains unchanged. The study also showed that, ibuprofen when administered with food delays the time taken for peak plasma concentration by somewhat 30-60 minutes.Distribut ionIbuprofen like the other instruments of its class is highly protein bound. It was found in a study that about 90-99% of ibuprofen was protein bound at a concentration of 20g/ml and this binding was non-linear. The volume of distribution ibuprofen changes with age and fever conditions. Studies reveal that febrile childrens less than 11 historic period old have volume of distribution approximately 0.2 L/kg, while adults have volume of distribution approximately 0.12 L/kg.MetabolismIbuprofen is extensively metabolised in the liver to form inactive metabolic compounds. Ibuprofen is mainly metabolised by glucoronidation reaction. A study showed that majority of the ibuprofen dose was recovered in the urine as hydroxy phenyl propionic acid (25%) and carboxy propyl phenyl propionic acid (37%) metabolites.EliminationIbuprofen and its inactive metabolites are rapidly and completely excreted by the kidney. About 95% of the administered dose of ibuprofen is eliminated in the urine. The e limination half-life of ibuprofen is in the range of 1.9 hours to 2 hours.Pharmacological activityIbuprofen has the following pharmacological actions on the biological systemAntipyretic effectAnalgesic effectAnti-inflammatory effectAntipyretic effectA normal body temperature is regulated by a centre in the hypothalamus that ensures a balance between heat loss and heat production in the body. Therefore, the hypothalamus maintains a normal temperature of the body and then it acts as a thermostat. When there is a disturbance in this hypothalamic thermostat, temperature of the body set by the hypothalamus is raised, fever occurs. Ibuprofen and other Non-steroidal anti-inflammatory drugs set this rise in the temperature. It regulates various temperature regulatory mechanisms such as dilation of superficial blood vessels, sweating etc. to reduce the temperature. Ibuprofen and other NSAIDs do not affect the normal temperature.Ibuprofen and other NSAIDs are thought to act as antipyretic a gents by inhibiting the prostaglandin production in the hypothalamus. During an inflammatory reaction, the bacterial endotoxins cause a release of a pyrogen-IL-1 from macrophages. This release of pyrogen stimulates the generation of E-type prostaglandins in the hypothalamus, this in turn causes the elevation of temperature. There are evidences that prostaglandins are not the only mediators of fever, hence ibuprofen and other NSAIDs may have some alternate mechanisms for their antipyretic activity which is not yet known.Analgesic effectIbuprofen is mainly telling against pain associated with inflammation or tissue damage. This is due to the inhibition of prostaglandins that sensitise nociceptors to inflammatory mediators such as bradykinin. Therefore ibuprofen is impressive against pains that are associated with change magnitude prostaglandin synthesis. Their ability to relieve headache may be related to the inhibition of the vasodilator effect of prostaglandins on the cerebral va sculature. There are some evidences that ibuprofen have a central effect by an action mainly in the spinal cord where it inhibits the COX-III enzyme. This action of ibuprofen is not yet clearly known.Anti-inflammatory activityMany chemical mediators are released when there is a stimulus of an inflammatory and allergic response. This response leads to vasodilation, increased vascular permeability, cell accumulation, etc., which are produced by several mechanisms. Furthermore, different mediators may be of particular importance in different inflammatory and allergic conditions. Ibuprofen reduces mainly those components of the inflammatory and immune response in which mediators produced by COX-II enzyme action plays a significant part. The components inhibited by ibuprofen are vasodilation, oedema and pain. Ibuprofen has no effect on those processes which contribute to tissue damage as in chronic inflammatory conditions such as rheumatoid arthritis, vasculitis and nephritis.Uses of ibu profenIbuprofen is utilise to treat a wide range of illnesses such as headaches, backache, menstrual cramps, dental pain, neuralgia, rheumatic pain, muscular pain, migraine, arthritis and athletic injuries. Ibuprofen is also used to reduce fever and to relieve minor aches and pain caused due to common cold or flu.In a recent study, it was found that ibuprofen was effective in the treatment of Alzheimers disease when given in low doses over a long period of time. A study also showed that ibuprofen is associated with a lower put on the line of Parkinsons disease, and ibuprofen may help in delaying and prevent it..Adverse effects of IbuprofenIbuprofen appears to havethelowestincidence of unfavourabledrugreactions(ADRs)when compared to all othernon-selectiveNSAIDs. However, this only holdstrueat lower doses of ibuprofen. Common adverseeffects of ibuprofen with the GI tract include nausea, dyspepsia, heartburn, gastrointestinal ulceration and bleeding, diarrhoea, loss of appetite, s tomach pain. Effects on central nervous system include headache, dizziness, fatigue and nervousness. Hypersensitivity reactions include skin rashes, itching. In very noble-minded cases ex-foliative dermatitis and epidermal necrolysis has been observed. Infrequentadverseeffect includes- oesophageal ulceration, heart failure, hyperkalaemia, renal impairment, confusion,bronchospasm, andsalt andfluid retention 11PhotosensitivityLike the other agents of the NSAIDs,ibuprofen has also been reported to bea photosensitisingagent.1213However, this only rarely occurs with ibuprofen andit is considered to bea very weak photosensitisingagentwhen compared with other members of Non-steroidal anti-inflammatory drugs. This is because theibuprofen molecule containsonly a single phenyl moiety andnobondconjugation,resultingin a very weak chromophore system anda very weak absorption spectrumwhichdoes not reachinto thesolar spectrum.Cardiovascular riskIbuprofen has been reported to elevate theriskof myo cardial infarction,particularly amongthose taking chronicallyhighdoses of ibuprofen 14 insecurity in pregnancyStudies havefound an increased riskof miscarriagewith theuse of ibuprofen in early pregnancy however, there are no thorough findings inthis association.There are alsoconcernsthat drugs suchas ibuprofen may interfere with implantation of theearly foetus, although a clear risk has not been established. When ibuprofen is used as directed in thefirstandsecond trimester of pregnancy,it is not associated with an increased riskfor birth defects. However, ibuprofen is generally not usedduringpregnancy because there are concernswith theiruse duringthethird trimester.Ibuprofen OverdoseIbuprofen is the most commonly and widely used Non-steroidal anti-inflammatory agent all over the world. Since, ibuprofen was licensed as an over the counter drug, ibuprofen o.d. became a common phenomenon.The most common symptoms of ibuprofen overdose are unsteadiness, blurred vision, ringing in the ea rs, gastrointestinal, nausea plus vomiting, diarrhoea, stomach pain, probable loss of blood in intestinal areas or stomach or both, headache, agitation, drowsiness, incoherence and confusion etc. Sometimes more serious symptoms are also noticed in some victims, such as seizure, gastrointestinal bleeding, metabolic acidosis, respiratory depression, hyperkalaemia, tachycardia, atrial fibrillation, coma, hepatic dysfunction, renal failure, cyanosis, and cardiac arrest etc., however these symptoms are very rare. Theseverity of symptoms varies with the ingested doseandthetime elapsed. However, individual sensitivity also playsan importantrole. Generally,thesymptoms observed with an overdoseof ibuprofen are similar to thesymptoms caused byan overdose of other NSAIDs.Doses of ibuprofen below 100 mg/kg are less likely to produce any toxic effects. But doses of ibuprofen above 400 mg/kg are considered an overdose and can result into any of the above consequences.