Analgesic

An analgesic, also known as a pain reliever, painkiller, or antalgic, is a type of drug used to manage pain. These drugs are different from anesthetics, which temporarily reduce or remove sensation, though the two categories overlap neurophysiologically, meaning some substances can act as both an analgesic and an anesthetic. The choice of analgesic often depends on the kind of pain involved. For nerve-related (neuropathic) pain, recent research indicates that medications not typically classified as analgesics—such as tricyclic antidepressants and anticonvulsants—might be used as alternatives.

Many analgesics, including most nonsteroidal anti-inflammatory drugs (NSAIDs), are available over the counter in many countries. Others require a prescription because of significant risks, including overdose, misuse, and addiction, without medical supervision.

The term "analgesic" comes from Greek roots: *an-* (without), *álgos* (pain), and *-ikos* (forming adjectives). Before the 20th century, such drugs were commonly called anodynes.

Analgesics are generally classified by how they work.

**Paracetamol (acetaminophen)** is used to treat pain and fever, typically for mild to moderate pain. When combined with opioid painkillers, it is also used for more severe pain, such as cancer pain or post-surgical pain. It can be taken orally, rectally, or intravenously, with effects lasting two to four hours. It is considered a mild analgesic and is generally safe at recommended doses.

**NSAIDs** are a class of drugs that reduce pain and fever, and at higher doses, also decrease inflammation. Common examples available over the counter in most countries include aspirin, ibuprofen, naproxen, and diclofenac.

**COX-2 inhibitors** were developed from NSAIDs. Researchers found that the cyclooxygenase enzyme blocked by NSAIDs has two versions: COX-1 and COX-2. Most NSAID side effects were linked to blocking COX-1, while pain relief came from blocking COX-2. COX-2 inhibitors were therefore designed to block only COX-2. Drugs like rofecoxib, celecoxib, and etoricoxib are as effective as NSAIDs but cause less gastrointestinal bleeding. However, after widespread use, most drugs in this class were found to increase the risk of cardiovascular events by about 40%. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib appears relatively safe, with a risk of thrombotic events similar to that of the non-coxib NSAID diclofenac.

**Opioids** include morphine and others like codeine, oxycodone, hydrocodone, dihydromorphine, and pethidine, all of which affect the brain’s opioid receptor system. Buprenorphine is a partial agonist of the μ-opioid receptor. Tramadol is a serotonin–norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor activity; it is structurally closer to venlafaxine than to codeine and works through both opioid-like effects and as a weak serotonin releaser and norepinephrine reuptake inhibitor. Tapentadol, similar in structure to tramadol, acts as both a traditional opioid and an SNRI. The roles of serotonin and norepinephrine in pain are not fully understood, but drugs in the SNRI class are often used with opioids (especially tapentadol and tramadol) for better pain relief.

Opioid dosing can be limited by toxicity, such as confusion, respiratory depression, myoclonic jerks, and pinpoint pupils, as well as seizures (particularly from tramadol). However, opioid-tolerant individuals usually tolerate higher doses. Opioids can cause unpleasant side effects: nausea and vomiting (often managed with antiemetics like phenergan), itching (which may require switching opioids), and constipation (almost universal, typically treated with laxatives like lactulose, macrogol, or co-danthramer). Opioid tolerance is different from opioid-induced hyperalgesia, where opioid use increases pain sensitivity and can make non-painful stimuli painful.

**Alcohol** has biological, mental, and social effects that influence its use for pain. Moderate use can reduce certain types of pain in some situations. Most of its analgesic effect comes from blocking NMDA receptors (similar to ketamine), which lowers the activity of the excitatory neurotransmitter glutamate. It also works to a lesser degree by increasing the activity of the inhibitory neurotransmitter GABA. Using alcohol for pain can lead to negative outcomes, including excessive drinking and alcohol use disorder.