Ibuprofen

BRAND NAME:

• Advil: Ibuprofen 200 mg, a non-steroidal anti-inflammatory drug that relieves pain and inflammation by reducing hormones, is the main ingredient in Advil tablets.

• Nuprin: It is available in 300 mg tablets of Dexibuprofen and is used to relieve pain. It works to treat heat and pain or inflammation caused by a wide range of ailments, including headaches, toothaches, back pain, arthritis, menstrual cramps, and minor injuries.

• Bruzen MR: Bruzen MR tablet is a combination of ibuprofen 400 mg and tizanidine 2 mg used to reduce pain caused by muscle contractions. It enhances muscle movement while also relieving the pain and suffering caused by muscle spasms.

• Maxofen Plus: It is a combination tablet of two painkiller medications (Ibuprofen 400 mg and paracetamol 333 mg). It is available in the market as Maxofen Plus.

MECHANISM OF ACTION:

Ibuprofen's primary mode of action is to suppress prostaglandin precursors. On a physiological or pathological stimulus, membrane phospholipids release arachidonic acid via the enzyme phospholipase A2. Arachidonic acid enters one of three enzymatic pathways: COX, LOX, and CYP450. The cyclooxygenase pathway transforms arachidonic acid into prostaglandins, prostacyclins, and thromboxane. The lipoxygenase pathway produces HETEs, leukotrienes, and lipoxins. Finally, the cytochrome P450 process transforms arachidonic acid into HETEs and epoxyeicosatrienoic acids (EET).

These mechanisms all produce eicosanoids. These molecules play a role in the intercellular and intracellular signaling of a variety of physiological processes, including smooth muscle tone modulation, vascular permeability, transporter proteins, platelet aggregation, and cell proliferation. Eicosanoids, including other products of the cyclooxygenase system, are involved in autoimmunity, angiogenesis, atopy, and inflammatory conditions. Ibuprofen indicated application depends mainly on the cyclooxygenase pathway. The COX pathway produces three different isoforms: COX-1 (PGH synthase), COX-2, and COX-3. COX-1 is a constitutionally expressed isoform that levels remain relatively steady in response to most physiological or pathologic actions. In contrast, mitogenic and inflammatory stimuli highly stimulate COX-2 expression. Acetaminophen inhibits the activity of COX-3.

Inhibiting the COX-1 and COX-2 pathways lowers the generation of prostaglandin precursors, which reduces the cellular response to pathologic or physiological stimuli. Nonselective NSAIDs, including ibuprofen, derive their antipyretic, anti-inflammatory, and analgesic effects from this mechanism. For ibuprofen, particularly, COX-1 is inhibited roughly 2.5 times more strongly than COX-2, indicating the need for study on the efficacy of COX-2 selective inhibitors in treating disorders typically treated with ibuprofen.

PHARMACOKINETICS:

• Absorption: Ibuprofen is fast and completely absorbed upon oral ingestion. Food consumption, however, can have an impact on absorption due to variations in stomach pH, emptying, and motility. When administrated with meals, its maximum plasma concentration (Cmax) decreases by 30%-50%, and the time to achieve maximum concentration (Tmax) increases by 30-60 minutes.

• Distribution: Ibuprofen is highly bound to plasma proteins, with approximately 99% bound once absorbed.

• Metabolism: Ibuprofen is primarily metabolized into hydroxylated and carboxylated compounds, which are the major forms of its metabolites. CYP2C9 and CYP2C8 are the primary CYP enzymes responsible for ibuprofen clearance.

• Elimination: Ibuprofen is predominantly eliminated in the urine as metabolites and conjugates. Approximately one percent of the original medication is excreted unchanged.

PHARMACODYNAMICS:

Ibuprofen acts on many inflammatory pathways involved in both acute and chronic inflammation. The primary actions of ibuprofen are related to the regulation of pain, fever, and acute inflammation by inhibiting the synthesis of prostanoids by COX-1 and COX-2. Pain alleviation is linked to peripherally impacted regions and central nervous system changes in pain transmission via the dorsal horn and upper spinothalamic tract. Some studies have attempted to link pain modulation to a potential increase in endogenous cannabinoids production and NMDA receptor activity. The effect on pain was revealed to be connected to the cortically elicited potential.

DOSAGE AND ADMINISTRATION

Ibuprofen is available over-the-counter in the majority of nations in a range of dosage forms, such as topical gels, intravenous solutions, chewable tablets, oral capsules, oral suspensions, and combo kits. Lysine and ibuprofen are a commonly used intravenous combination. Although it can be given via the same IV line, ibuprofen and total parenteral nutrition shouldn't be given at the same time. Complete parenteral feeding should be halted 15 minutes before ibuprofen administration and restarted 15 minutes later. Oral ibuprofen should be taken with food or milk. Intravenous injection is frequently chosen in inpatient settings or when oral delivery is impossible. Infusions must last at least 30 minutes for adults and 10 minutes in pediatric patients.

For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis, take 1800–2400 mg daily. Higher dosages of 400 to 800 mg taken orally every six hours, not to exceed 3200 mg daily, may be prescribed by physicians.200–400 mg taken orally every 4–6 hours, up to a daily cap of 1200 mg, unless prescribed by a physician. 

CONTRAINDICATIONS:

Ibuprofen should not be used by patients who have a history of hypersensitivity or adverse responses to the medicine, other NSAIDs, or aspirin. Several case studies have shown ibuprofen as a disease precipitant. NSAIDs are among the drugs most commonly related to hypersensitivity events in both adult and pediatric patients. These individuals are usually diagnosed with urticaria or angioedema caused by cross-intolerance to other medication classes, especially quinolones and amoxicillin-clavulanic acid.

DRUG INTERACTIONS:

ACE Inhibitors: Ibuprofen may decrease the antihypertensive effects of ACE inhibitors. Monitoring is suggested for patients who use these drugs simultaneously.

Aspirin: Ibuprofen can interfere with aspirin's antiplatelet actions, particularly if these drugs are taken concurrently or before aspirin. To avoid this interaction, use immediate-release low-dose aspirin at least 2 hours before ibuprofen. Concurrent use is generally discouraged due to increased cardiovascular risks.

Diuretics: Ibuprofen reduces the natriuretic action of diuretics like furosemide and thiazides, potentially lowering their efficacy.

Anticoagulants: Ibuprofen enhances the risk of gastrointestinal bleeding in people on warfarin treatment.When using these drugs together, patients should be closely monitored for indications of bleeding.

SIDE EFFECTS:

Common side effects for ibuprofen include:

• Abdominal pain

• acid or sour stomach

• belching

• bloating

• decrease urine volume

• heartburn

• indigestion

• itching skin

• chest, upper stomach, or throat pain

• unusual tiredness or weakness

• vomiting

OVERDOSE:

Signs of overdose include:

• Diarrhea

• Heartburn

• Low blood pressure and weakness

• Kidney damage might cause decreased urine production.

• Sweating

• Stomach ulcers and bleeding

• Blurred vision

TOXICITY:

Ibuprofen's toxic potential is derived from its inhibition of the cyclooxygenase pathway and the subsequent effects on various cellular processes and multiple organ systems. Prostaglandins and thromboxanes help maintain the gastric mucosal layer and renal blood flow; ibuprofen is associated with a mildly elevated risk of adverse gastrointestinal and renal events, even at therapeutic levels. Ibuprofen is the most common NSAID involved in overdose cases; 29% of overdoses are the result of ibuprofen ingestion alone. Patients can also overdose by ingesting ibuprofen combined with other analgesics.One study created a risk score for improving the risk-benefit ratio of NSAID administration; this score was accurate in categorizing the one-year risk of significant toxicity among NSAID users.

STORAGE CONDITIONS:

Maintain 20̊C to 25̊C (68̊ F to 77̊F), excursion permitted to 15̊ C to 30̊C. Avoid excessive heat 40̊C (104̊F).