Analgesic

An analgesic, also known as a painkiller, pain reliever, or antalgic, is a type of drug used to manage pain. These drugs are different from anesthetics, which temporarily reduce or eliminate sensation, though the two categories overlap neurophysiologically, meaning some drugs can produce both analgesic and anesthetic effects. The choice of analgesic depends on the type of pain. For neuropathic pain, recent research suggests that drugs not typically considered analgesics, such as tricyclic antidepressants and anticonvulsants, may be used as alternatives. Many analgesics, like most NSAIDs, are available over the counter in many countries, while others require a prescription due to risks of overdose, misuse, and addiction without medical supervision. The word "analgesic" comes from Greek roots: an- ("without"), álgos ("pain"), and -ikos (forming adjectives). Before the 20th century, these drugs were commonly called "anodynes." Analgesics are usually classified by their mechanism of action. Paracetamol (acetaminophen) is used for pain and fever, typically for mild to moderate pain. For more severe pain, such as cancer pain or post-surgery pain, it is combined with opioid pain medication. It is taken by mouth, rectally, or intravenously, with effects lasting two to four hours. It is considered a mild analgesic and is generally safe at recommended doses. (nonsteroidal anti-inflammatory drugs) reduce pain and fever, and at higher doses, decrease inflammation. Common examples like aspirin, ibuprofen, naproxen, and diclofenac are available over the counter in most countries. COX-2 inhibitors were developed from NSAIDs. Research found that the cyclooxygenase enzyme has two versions: COX-1 and COX-2. Blocking COX-1 was linked to many NSAID side effects, while blocking COX-2 provided pain relief. COX-2 inhibitors (e.g., rofecoxib, celecoxib, etoricoxib) target only COX-2, making them as effective as NSAIDs but with less gastrointestinal bleeding. However, most drugs in this class were found to increase cardiovascular event risk by about 40%, leading to the withdrawal of rofecoxib and valdecoxib and warnings on others. Etoricoxib appears relatively safe, with a thrombotic risk similar to the non-coxib NSAID diclofenac. Opioids include morphine, codeine, oxycodone, hydrocodone, dihydromorphine, and pethidine, all acting on the cerebral opioid receptor system. Buprenorphine is a partial μ-opioid receptor agonist, while tramadol is a serotonin–norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor activity. Tramadol is structurally closer to venlafaxine than codeine and works through mild opioid-like effects and as a weak, fast-acting serotonin releaser and norepinephrine reuptake inhibitor. Tapentadol, similar to tramadol, acts through both traditional opioid and SNRI mechanisms. The effects of serotonin and norepinephrine on pain are not fully understood, but SNRIs are often used with opioids (especially tapentadol and tramadol) for better pain relief. Opioid dosing can be limited by toxicity (confusion, respiratory depression, myoclonic jerks, pinpoint pupils) or seizures (particularly from tramadol), though opioid-tolerant individuals usually tolerate higher doses. Side effects include nausea and vomiting (often treated with antiemetics like phenergan), itching (which may require switching opioids), and constipation (almost universal, typically managed with laxatives like lactulose, macrogol, or co-danthramer). Opioid tolerance is different from opioid-induced hyperalgesia, where opioid exposure increases pain sensation (hyperalgesia) or makes non-painful stimuli painful (allodynia). Alcohol has biological, mental, and social effects that influence its use for pain. Moderate alcohol use can lessen certain types of pain in some circumstances. Its analgesic effects mostly come from antagonizing NMDA receptors (similar to ketamine), reducing glutamate activity, and to a lesser degree, increasing GABA activity. Using alcohol for pain can lead to negative outcomes, including excessive drinking.