Cox-2 selective nonsteroidal anti-inflammatory drugs

In individuals aged 65 years or more, the most common causes of dementia after AD are Lewy body disease (LBD) and cerebrovascular disease (VaD). Both LBD and VaD have symptoms that overlap with those of AD. Moreover, LBD and VaD pathology are often found combined with AD pathology in autopsy samples. In younger patients, frontotemporal lobar degeneration (FTLD) and dementia from chronic alcohol use are also common. 11 Most of these entities can be differentiated from AD by detailed clinical history, careful examination, and attention to diagnostic criteria. Potentially treatable conditions that can mimic or exacerbate AD dementia include depression, hypothyroidism, vitamin B 12 deficiency, hypocalcemia, neurosyphilis (in endemic regions), and normal pressure hydrocephalus. Certain medications, particularly those with anticholinergic, amnestic, or sedating properties, can be cognitoxic. 12 Symptoms and signs that suggest non-AD etiologies are listed in Table 2 .

Systemic ketorolac, like all nonsteroidal anti-inflammatory drugs (NSAIDs), may exacerbate hypertension and congestive heart failure and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. The FDA has warned that the risk of myocardial infarction or stroke can occur as early as the first weeks of using a NSAID, and risk may increase with higher doses and longer duration of use. Data demonstrate that patients treated with NSAIDs were more likely to die in the first year following a myocardial infarction compared to those not treated with NSAIDs. NSAIDs may increase the risk of a cardiovascular thrombotic event in patients with or without underlying heart disease or risk factors for heart disease. Patients with known heart disease or risk factors appear to have a greater likelihood of an event following NSAID use, likely due to a higher baseline risk. Current evidence is insufficient to determine if the risk of an event is higher or lower for any particular NSAID compared to other NSAIDs. There is an increased risk of heart failure with NSAID use. Caution is recommended when administering systemic ketorolac to patients with cardiac disease, cardiomyopathy, cardiac arrhythmias (., tachycardia), significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (., stroke, transient ischemic attack), hypertension, pre-existing renal disease, or fluid retention. In addition, clinical practice guidelines state NSAIDs should not be administered to patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use. Closely monitor blood pressure during ketorolac receipt. An increase in cardiovascular risk is not expected with ophthalmic use. Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or symptoms of a cardiovascular thrombotic event.

It may be that the greatest risk of inducing a myocardial infarction is in a patient with undiagnosed coronary vascular disease. Before COX-2 selective inhibitors became available, this patient may have been prescribed another NSAID. This would have had an aspirin-like antiplatelet effect and, if anything, might have been expected to reduce the risk of infarction. If the patient is instead commenced on a COX-2 selective inhibitor the balance swings towards a prothrombotic state that theoretically might result in an infarction. This theoretical point is supported by the results of the VIGOR study and the termination of the APPROVe study because of an excess risk of myocardial infarction and stroke in patients taking rofecoxib for 18 months.

Concerns have been raised about increased cardiovascular risk with the use of COX-2 inhibitors. The ACG 22 and the Canadian Association of Gastroenterology 24   have each developed evidence-based guidelines for the prevention of NSAID-related ulcers in patients at risk of cardiovascular disease, including those with previous cardiovascular events. The recommendations are summarized in Table 4 . 22 , 24 NSAIDs are appropriate for patients with low risk of gastrointestinal complications, whereas cotherapy with a PPI or misoprostol is preferred for patients with gastrointestinal risk factors. 22 , 24 Patients at low cardiovascular risk may take traditional NSAIDs or a COX-2 inhibitor; however, the Canadian Association of Gastroenterology suggests that the use of naproxen may be appropriate for patients at high cardiovascular risk. 22 , 24

Cox-2 selective nonsteroidal anti-inflammatory drugs

cox-2 selective nonsteroidal anti-inflammatory drugs

Concerns have been raised about increased cardiovascular risk with the use of COX-2 inhibitors. The ACG 22 and the Canadian Association of Gastroenterology 24   have each developed evidence-based guidelines for the prevention of NSAID-related ulcers in patients at risk of cardiovascular disease, including those with previous cardiovascular events. The recommendations are summarized in Table 4 . 22 , 24 NSAIDs are appropriate for patients with low risk of gastrointestinal complications, whereas cotherapy with a PPI or misoprostol is preferred for patients with gastrointestinal risk factors. 22 , 24 Patients at low cardiovascular risk may take traditional NSAIDs or a COX-2 inhibitor; however, the Canadian Association of Gastroenterology suggests that the use of naproxen may be appropriate for patients at high cardiovascular risk. 22 , 24

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