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While the use of paracetamol, aspirin, ibuprofen, naproxen, and other NSAIDS concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combating pain at multiple sites of action, [29] [30] several combination analgesic products have been shown to have few efficacy ...
The combinations of paracetamol and NSAIDs ibuprofen or diclofenac are promising, possibly offering better pain control than either paracetamol or the NSAID alone. [25] [26] [68] [69] Additionally, the paracetamol/ibuprofen combination may be superior to paracetamol/codeine and ibuprofen/codeine combinations. [26]
Naproxen's medical uses are related to its mechanism of action as an anti-inflammatory compound. [11] Naproxen is used to treat a variety of inflammatory conditions and symptoms that are due to excessive inflammation, such as pain and fever (naproxen has fever-reducing, or antipyretic, properties in addition to its anti-inflammatory activity). [11]
Ibuprofen/paracetamol, sold under the brand name Combogesic among others, is a fixed-dose combination of two medications, ibuprofen, a non-steroidal anti-inflammatory drug (NSAID); and paracetamol (acetaminophen), an analgesic and antipyretic. [6] It is available as a generic medication. [9] [10] [11]
Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity. Paracetamol treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, and only minimally in the rest of the body. [15] [16]
The WHO guidelines recommend prompt oral administration of drugs ("by the mouth") when pain occurs, starting, if the patient is not in severe pain, with non-opioid drugs such as paracetamol (acetaminophen) or aspirin, [1] with or without "adjuvants" such as non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors.
[23] [24] [25] They may also have applications in the treatment of neuroinflammation. [13] [16] The anti-inflammatory effects of psychedelics may be involved in the effects of psychedelic microdosing. [26] [27] Relatedly, LSD microdosing is being studied in the treatment of Alzheimer's disease for its anti-inflammatory effects. [28] [29]
Several CINODs are currently being tested in clinical trials, the most advanced of which are being conducted by the French pharmaceutical company NicOx, whose flagship compound naproxcinod (NO-naproxen, nitronaproxen) is in phase III trials for the treatment of osteoarthritis. [6] Naproxcinod is a fusion of naproxen and a NO-donating group ...