● Diuretics: The effectiveness of diuretics in people with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. ● Methotrexate: Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in the elderly or renal impaired. ● Nonsteroidal anti-inflammatory drugs (NSAIDs): The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. ● Oral hypoglycemics : Moderate doses of aspirin may increase the effectiveness of oral hypoglycemic drugs, leading to hypoglycemia. ● Uricosuric agents (probenecid and sulfinpyrazone): Salicylates antagonize the uricosuric action of uricosuric agents. ● Carcinogenesis, mutagenesis, impairment of fertility: Administration of aspirin for 68 weeks at 0.5 percent in the feed of rats was not carcinogenic. In the Ames Salmonella assay, aspirin was not mutagenic; however, aspirin did induce Side effects Many adverse reactions due to aspirin ingestion are dose- related. The following is a list of adverse reactions that have been reported in the literature: ● General: Fever, hypothermia, thirst. ● Cardiovascular: Dysrhythmias, hypotension, tachycardia. ● Central nervous system : Agitation, cerebral edema, coma, confusion, dizziness, headache, subdural or intracranial hemorrhage, lethargy, seizures. ● Fluid and electrolyte : Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis. ● Gastrointestinal : Dyspepsia, GI bleeding, ulceration and perforation, nausea, vomiting, transient elevations of hepatic enzymes, hepatitis, Reye’s syndrome, pancreatitis. ● Hematologic : Prolongation of the prothrombin time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia. ● Hypersensitivity : Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria. ● Musculoskeletal : Rhabdomyolysis. ● Metabolism : Hypoglycemia (in children), hyperglycemia. ● Reproductive : Prolonged pregnancy and labor, stillbirths, lower birth weight infants, antepartum and postpartum bleeding. ● Respiratory : Hyperpnea, pulmonary edema, tachypnea. ● Special senses : Hearing loss, tinnitus. People with high frequency hearing loss may have difficulty perceiving tinnitus.
chromosome aberrations in cultured human fibroblasts. Aspirin inhibits ovulation in rats. (See Pregnancy.) ● Pregnancy: Pregnant women should only take aspirin if clearly needed. Because of the known effects of NSAIDs on the fetal cardiovascular system (closure of the ductus arteriosus), use during the third trimester of pregnancy should be avoided. Salicylate products have also been associated with alterations in maternal and neonatal hemostasis mechanisms, decreased birth weight, and with perinatal mortality. ● Labor and delivery: Aspirin should be avoided 1 week prior to and during labor and delivery because it can result in excessive blood loss at delivery. Prolonged gestation and prolonged labor due to prostaglandin inhibition have been reported. ● Nursing mothers: Nursing mothers should avoid using aspirin because salicylate is excreted in breast milk. Use of high doses may lead to rashes, platelet abnormalities, and bleeding in nursing infants. ● Pediatric use: Pediatric dosing recommendations for juvenile rheumatoid arthritis are based on well-controlled clinical studies. ● Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure. ● Nonacetylated salicylates: Magnesium salicylate (Doan’s pills) sodium salicylate, and salicylate (Disalcid). All nonacetylated salicylates are useful anti-inflammatories, although they may be less effective analgesics than aspirin. There are significantly less effective than aspirin as cyclooxygenase inhibitors, so are more desirable when cyclooxygenase inhibition is not wanted, which is the case in individuals with asthma, bleeding tendencies and renal dysfunction. Individuals taking nonacetylated salicylates should be monitored for serum salicylate levels. In the past several years, some newer medications have come on the market that are commonly referred to as COX- 2 inhibitors . All NSAIDs work against cyclooxygenase (COX). Traditional NSAIDs (e.g. Ibuprofen, Motrin, Aleve) work against both COX-1 and COX-2. COX-1 and COX-2 are both types of cyclooxygenase enzymes that function in the body. The new medications (which included Celebrex, Vioxx, and Bextra, among others) only work against COX-2, and allow COX-1 to function normally. Because COX-1 is more important in producing the protective lining in your gut (gastric mucosa), these newer NSAIDs are believed to have less of a risk of causing stomach ulcers. That said, the newer NSAIDs have not been shown to work any better against the COX-2 enzyme. Therefore, the COX-2 inhibitors have the benefit of possibly having fewer side effects, but not necessarily better relief from symptoms. This reduction in the stomach lining can cause stomach ulceration and bleeding from the stomach and intestines. Cyclooxygenase-2 (COX-2) also produces these chemical messenger molecules, but the COX-2 enzyme is located specifically in areas of the body that are responsible for inflammation, and not in the stomach. A COX-2 inhibitor blocks the enzyme and inflammation is reduced. Since the COX-2 enzyme does not affect the normal function of the stomach or intestinal tract, medications that selectively block COX-2 do not present the same risk of injuring the stomach or intestines. However, they do cause a significant increase in cardiovascular risk such as stroke or heart attack. COX-2 plays a significant role in the development of various symptoms and conditions, including fever, inflammation, and pain. Its role in other conditions, such as cancer and Alzheimer’s dementia, also is being investigated.
COX-2 selective inhibitors (Coxibs) Celecoxib (Celebrex) etoricoxib, meloxicam.
COX-2 inhibitors achieve inflammation reduction by selectively blocking the COX-2 enzyme, which obstructs the production of the prostaglandins (chemical messengers) that cause the pain and swelling of arthritis inflammation. COX-2 inhibitors do not block the COX-1 enzyme, making them uniquely different from traditional NSAIDs. Cyclooxygenase-1 (COX-1) is an enzyme normally present in a variety of areas of the body, including sites of inflammation and the stomach. The COX-1 enzyme of the stomach produces certain chemical messengers (called prostaglandins ) that ensure the natural mucus lining which protects the inner stomach. Common anti-inflammatory drugs like aspirin block the function of the COX-1 enzyme along with another enzyme, COX-2. Inflammation is reduced when the COX-1 enzyme is blocked, but the protective mucus lining of the stomach is also reduced.
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