Tr-I-LIfe

Aspirin, ibuprofen, naproxen, and many other non-steroidal anti-inflammatory drugs (NSAIDs) work as COX inhibitors.  They suppress the catalytic functions of the enzymes COX1 and COX2.  COX2, which appears up injuries and other inflammatory stimuli, is deemed “bad”.  It catalyzes the synthesis of prostaglandins that, located near sites of injuries, cause pain and inflammation.  Inhibition of COX2 is responsible for the therapeutic effects of reducing pain, inflammation, and fever.  COX1, which is present in many parts of the body, is deemed “good.”  It catalyzes the synthesis of prostaglandins that perform many physiological functions, e.g., maintaining the mucus lining of the stomach or causing platelets in the blood to stick and form clots over wounds.  Inhibition of COX1 is responsible for the drugs’ side effect of stomach irritation.  In reducing the risk of blood clots, it is also responsible for aspirin’s efficacy in heart attack prevention.  A new class of NSAID, COX2 inhibitor, is designed to target bad COX2 selectively and leave good COX1 alone, thus reducing pain and inflammation without upsetting the stomach.

ASPIRIN:

Pharmacology

Inhibits prostaglandin synthesis, resulting in analgesia, anti-inflammatory activity, and platelet aggregation inhibition; reduces fever by acting on the brain’s heat-regulating center to promote vasodilation and sweating.

Pharmacokinetics

Absorption

Rapidly and completely absorbed. T _max is 1 to 2 h (salicylic acid).

Distribution

Widely distributed to all tissues and fluids, including CNS, breast milk, and fetal tissues. Approximately 90% of salicylate is protein bound at concentrations of less than 100 mcg/mL and approximately 75% is bound at concentrations of more than 400 mcg/mL.

Metabolism

Rapidly hydrolyzed to salicylic acid (active). Salicylic acid is conjugated in the liver to the metabolites.

Elimination

Salicylic acid plasma half—life is approximately 6 h, but may exceed 20 h in higher doses. The half—life is approximately 15 to 20 min for aspirin. Elimination follows zero-order kinetics. Renal elimination of unchanged drug depends on urine pH. A pH of more than 6.5 increases renal Cl of free salicylate from less than 5% to more than 80%.

Indications and Usage

Treatment of mild to moderate pain; fever; various inflammatory conditions; reduction of risk of death or MI in patients with previous infarction or unstable angina pectoris, or recurrent transient ischemia attacks (TIAs) or stroke in men who have had transient brain ischemia caused by platelet emboli.

Unlabeled Uses

Prevention of cataract formation; prevention of toxemia of pregnancy; improvement of inadequate uteroplacental blood flow in pregnancy; prophylaxis against thromboembolic events in patients with atrial fibrillation, mitral valve prolapse, peripheral arterial disease, bioprosthetic or mechanical heart valves, and in pregnant patients with prosthetic heart valves; antithrombotic therapy in children with Blalock-Taussig shunt or ischemic stroke, and in children after Fontan surgery.

Contraindications

Hypersensitivity to salicylates or NSAIDs; hemophilia, bleeding ulcers, or hemorrhagic states

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IBUPROFEN:

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

Pharmacokinetics

Absorption

T _max is 1 to 2 h (oral). Bioavailability is less than 80% (oral). C _max is 39.2 mcg/mL and 72.6 mcg/mL for a 400 and 800 mg IV dose, respectively.

Distribution

Highly protein bound.

Elimination

Plasma half-life is 1.8 to 2 h (oral) and 2.22 to 2.44 h (IV). 45% to 79% is eliminated through the urine (oral). Cl is 3 to 35 L/h (oral).

Indications and Usage

IV : In adults for the management of mild to moderate pain and as an adjunct to opioid analgesics in the management of moderate to severe pain. PO : Relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, mild to moderate pain, primary dysmenorrhea, reduction of fever, migraine.

Contraindications

Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; hypersensitivity to any component of the product.