An analgesic or painkiller is any member of the group of drugs
used to achieve analgesia, relief from pain
. They are distinct from anesthetic
s, which temporarily affect, and in some instances completely eliminate, sensation
Analgesic choice is also determined by the type of pain: For neuropathic pain
, traditional analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants
Analgesics are typically classified based on their mechanism of action.
Paracetamol, also known as acetaminophen or APAP, is a medication used to treat pain
It is typically used for mild to moderate pain.
In combination with opioid pain medication
, paracetamol is now used for more severe pain such as cancer pain
and after surgery. It is typically used either by mouth or rectally
but is also available intravenously
Effects last between two and four hours.
Paracetamol is classified as a mild analgesic.
Paracetamol is generally safe at recommended doses.
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a drug class
that groups together drug
s that decrease pain
and lower fever
, and, in higher doses, decrease inflammation
The most prominent members of this group of drugs, aspirin
, are all available over the counter
in most countries.
These drugs have been derived from NSAIDs. The cyclooxygenase
enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 (constitutive
) enzyme, with the analgesic effects being mediated by the COX2 (inducible
) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as rofecoxib
, and etoricoxib
) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.
After widespread adoption of the COX-2 inhibitors, it was discovered that most of the drugs in this class increase the risk of cardiovascular event
s by 40% on average. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib seems relatively safe, with the risk of thrombotic
events similar to that of non-coxib NSAID diclofenac.
, the archetypal opioid
, and other opioids (e.g., codeine
) all exert a similar influence on the cerebral opioid receptor
is a partial agonist
of the μ-opioid receptor, and tramadol
is a serotonin norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor agonist properties. Tramadol
is structurally closer to venlafaxine
than to codeine
and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the mu receptor
) but also by acting as a weak but fast-acting serotonin releasing agent
and norepinephrine reuptake inhibitor
, with some structural similarities to tramadol, presents what is believed to be a novel drug working through two (and possibly three) different modes of action in the fashion of both a traditional opioid and as an SNRI. The effects of serotonin and norepinephrine
on pain, while not completely understood, have had causal links established and drugs in the SNRI class are commonly used in conjunction with opioids (especially tapentadol and tramadol) with greater success in pain relief.
Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, myoclonic jerks
and pinpoint pupils), seizures (tramadol
), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance.
Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine may experience nausea
(generally relieved by a short course of antiemetic
s such as phenergan
(itching) may require switching to a different opioid. Constipation
occurs in almost all patients on opioids, and laxative
-containing or co-danthramer) are typically co-prescribed.
[Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).]
When used appropriately, opioids and other central analgesics are safe and effective; however, risks such as addiction and the body's becoming used to the drug (tolerance) can occur. The effect of tolerance means that frequent use of the drug may result in its diminished effect. When safe to do so, the dosage may need to be increased to maintain effectiveness against tolerance, which may be of particular concern regarding patients suffering with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with opioid rotation therapy
in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect.
Opioid tolerance should not be confused with opioid-induced hyperalgesia
. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain (hyperalgesia
) and can even make non-painful stimuli painful (allodynia
Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.
Moderate use of alcohol can lessen certain types of pain in certain circumstances.
The majority of its analgesic effects come from antagonizing NMDA receptors, similarly to ketamine, thus decreasing the activity of the primary excitatory (signal boosting) neurotransmitter, glutamate. It also functions as an analgesic to a lesser degree by increasing the activity of the primary inhibitory (signal reducing) neurotransmitter, GABA.
Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder
''Medical cannabis'', or ''medical marijuana'', refers to cannabis
or its cannabinoids
used to treat disease or improve symptoms. There is evidence suggesting that cannabis can be used to treat chronic pain
and muscle spasms
, with some trials indicating improved relief of neuropathic pain over opioids.
Analgesics are frequently used in combination, such as the paracetamol
preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as pseudoephedrine
-related preparations, or with antihistamine
drugs for allergy sufferers.
While the use of paracetamol, aspirin, ibuprofen
, 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 combatting pain at multiple sites of action,
several combination analgesic products have been shown to have few efficacy benefits when compared to similar doses of their individual components. Moreover, these combination analgesics can often result in significant adverse events, including accidental overdoses, most often due to confusion that arises from the multiple (and often non-acting) components of these combinations.
There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than placebo
The available research concludes that more research would be necessary to better understand the use of alternative medicine.
—a monoamine reuptake inhibitor, and calcium and sodium channel modulator—is also approved for the treatment of moderate to severe pain in some countries.
is a centrally acting K+ channel opener with weak NMDA antagonist
properties. It was used in Europe for moderate to strong pain, as well as its migraine
-treating and muscle-relaxant properties. It has no significant anticholinergic
properties, and is believed to be devoid of any activity on dopamine, serotonin, or histamine receptors. It is not addictive, and tolerance usually does not develop. However, tolerance may develop in some cases.
, a blocker of potent N‐type voltage‐gated calcium channels
, is administered intrathecally
for the relief of severe, usually cancer-related pain.
Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as amitriptyline
) and newer antidepressants (such as duloxetine
) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using hydroxyzine
, or tripelennamine
to increase the pain-killing ability of a given dose of opioid analgesic.
Adjuvant analgesics, also called atypical analgesics, include orphenadrine
(scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.
has been noted to slow the development of and reverse tolerance to opioids, as well as to exert additional analgesia by acting upon NMDA
receptors, as does ketamine
. Some analgesics such as methadone
and perhaps piritramide
have intrinsic NMDA action.
, two forms of which were found in the US Pharmacopoeia up until 1916 and in common use by physicians well into the 1930s, has been used in the past as an agent for dulling pain, due to the CNS
depressant effects of ethyl alcohol
, a notable example being the American Civil War
. However, the ability of alcohol to relieve severe pain is likely inferior to many analgesics used today (e.g., morphine, codeine). As such, in general, the idea of alcohol for analgesia is considered a primitive practice in virtually all industrialized countries today.
The anticonvulsant carbamazepine
is used to treat neuropathic pain. Similarly, the gabapentinoid
are prescribed for neuropathic pain, and phenibut is available without prescription. Gabapentinoids work as α2δ-subunit blockers of voltage-gated calcium channel
s, and tend to have other mechanisms of action as well. Gabapentinoids are all anticonvulsant
s, which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system.
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen
- or diclofenac
-containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity.); capsaicin
also is used topical
, an anesthetic
, and steroids
may be injected into joints for longer-term pain relief. Lidocaine is also used for painful mouth sore
s and to numb areas for dental
work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the bloodstream when applied in large doses to the skin without medical supervision. These topical anesthetics contain anesthetic drugs such as lidocaine, tetracaine, benzocaine, and prilocaine in a cream, ointment, or gel.
Topical nonsteroidal anti-inflammatory drugs
provide pain relief in common conditions such as muscle sprains and overuse injuries. Since the side effects are also lesser, topical preparations could be preferred over oral medications in these conditions.
Each different type of analgesic has its own associated side effects.
List of drugs with comparison
The word ''analgesic'' derives from Greek
''an-'' (, "without"), ''álgos'' (, "pain"),
and ''-ikos'' (, forming adjective
s). Such drugs were usually known as anodyne
s before the 20th century.
Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blocker
s such as funapide
, as well as multimodal agents such as ralfinamide
* Pain management
* Patient-controlled analgesia
* Pain in babies
* Congenital analgesia
(insensitivity to pain)