Cardiovascular risk ibuprofen

Along with several other NSAIDs, long-term use of ibuprofen has been found to be associated with a lower risk of developing hypertension in women, but lower than acetaminophen and myocardial infarction (heart attack) risk, especially in women who use higher doses long-term.On July 9, 2015, the FDA strengthened its warning about the increased risk of heart attack and stroke associated with ibuprofen and related NSAIDs; the NSAID aspirin was not included in this warning.The European Medicines Agency (EMA) issued a similar warning in 2015.

Skins 

Along with other NSAIDs, ibuprofen has been associated with flare-ups of bullous pemphigoid or pemphigoid-like blisters.Like other NSAIDs, ibuprofen has been reported to be a photosensitizer but compared to other members of the 2-arylpropionic acid class it is thought to be a weak photosensitizer agent.Like other NSAIDs, ibuprofen is an extremely rare cause of the autoimmune disease Stevens-Johnson syndrome (SJS),Ibuprofen is also an extremely rare cause of toxic epidermal necrolysis.

Interactive

Alcohol

Drinking alcohol while taking ibuprofen may increase risk of stomach bleeding.

Aspirin

According to the FDA, “ibuprofen interferes with the antiplatelet effects of low-dose aspirin and may make aspirin less effective when used for cardioprotection and stroke prevention.”Allowing enough time between taking ibuprofen and immediate-release (IR) aspirin can avoid this problem.The recommended interval between a dose of ibuprofen and a dose of aspirin depends on which one is taken first.Take ibuprofen 30 minutes or more after the IR aspirin and 8 hours or more before the IR aspirin.However, this timing is not recommended for enteric-coated aspirin.However, if ibuprofen is taken only occasionally and not at the recommended time, the effect of a daily aspirin regimen on heart protection and stroke prevention is minimal.

Paracetamol

Ibuprofen plus paracetamol considered generally safe for short-term use in children.

Overdose

Overdoses of ibuprofen have become common since ibuprofen was licensed for over-the-counter use.Although the frequency of life-threatening complications from ibuprofen overdose is low, numerous overdose experiences have been reported in the medical literature.Despite intensive care, human responses to overdose range from asymptomatic to fatal outcomes.Most of the symptoms were the pharmacological effects of ibuprofen, including abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, tinnitus, and nystagmus.Rarely more serious symptoms such as gastrointestinal bleeding, seizures, metabolic acidosis, hyperkalemia, hypotension, bradycardia, tachycardia, atrial fibrillation, coma, liver dysfunction, acute renal failure, cyanosis, Respiratory depression and cardiac arrest have been reported.The severity of symptoms varies with the dose and timing of ingestion; however, personal sensitivity also plays an important role.In general, symptoms observed with ibuprofen overdose are similar to symptoms caused by overdose with other NSAIDs.The correlation between symptom severity and measured ibuprofen plasma levels was weak.Toxic effects are unlikely at doses below 100 mg/kg but may be severe above 400 mg/kg (approximately 150 tablets of 200 mg units for an average person);however, Higher doses do not imply a potentially fatal clinical course.The precise lethal dose is difficult to determine because it may vary with age, body weight, and individual concomitant conditions.

Treatment to resolve ibuprofen overdose depends on the presentation of symptoms. In cases of early onset, decontamination of the stomach is recommended.This is achieved using activated charcoal; the charcoal absorbs the drug before it enters the bloodstream. Gastric lavage is now rarely used, but may be considered if ingested in potentially life-threatening amounts and may be performed within 60 minutes of ingestion.Purposeful vomiting is not recommended.Most ibuprofen intake produces only minor effects, and overdose is simple to manage.Standard measures to maintain normal urine output and monitor renal function should be instituted. Since ibuprofen is acidic and excreted in urine, forced alkaline diuresis is theoretically beneficial.However, because ibuprofen is highly protein bound in the blood, renal excretion of the parent drug is minimal.Therefore, forced alkaline diuresis has limited effect.

Miscarriage

A Canadian study of pregnant women showed that those who took any type or amount of NSAIDs, including ibuprofen, diclofenac, and naproxen, were 2.4 times more likely to have a miscarriage than those who didn’t. [50] 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 cyclooxygenase (COX), the enzyme that converts arachidonic acid to prostaglandin H2 (PGH2).PGH2 is in turn converted by other enzymes into several other prostaglandins (mediators of pain, inflammation, and fever) and thromboxane A2 (stimulates platelet aggregation, leading to clot formation).Like aspirin and indomethacin, ibuprofen is a nonselective COX inhibitor because it inhibits two isoforms of cyclooxygenase, COX-1 and COX-2.The analgesic, antipyretic, and anti-inflammatory activities of NSAIDs appear to work primarily through inhibition of COX-2, which reduces the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling.The antipyretic effect may be due to an action on the hypothalamus, leading to increased peripheral blood flow, vasodilation and subsequent heat dissipation. Conversely, inhibition of COX-1 can have adverse effects on the gastrointestinal tract.However, the roles of individual COX isomers in the analgesic, anti-inflammatory and gastric injury effects of NSAIDs are uncertain, and different compounds cause different degrees of analgesia and gastric injury.

Ibuprofen is administered as a racemic mixture.The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is considered to be the more pharmacologically active enantiomer.The R-enantiomer is converted by 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 body.In addition to converting ibuprofen to the S-enantiomer, the body can metabolize ibuprofen to several other compounds, including a number of hydroxyl, carboxyl, and glucuronide metabolites. Virtually all of these have no pharmacological effect.Unlike most other NSAIDs, ibuprofen also acts as a Rho kinase inhibitor, which may aid recovery from spinal cord injuries.

Pharmacokinetics

Following oral administration, serum concentrations peak after 1-2 hours and up to 99% of the drug is bound to plasma proteins.The majority of ibuprofen is metabolized and eliminated via urine within 24 hours; however, 1% of parent drug is eliminated via biliary excretion.