Analgesics are typically classified based on their mechanism of action. |182x182px
Paracetamol (acetaminophen) Paracetamol, also known as acetaminophen or APAP, is a medication used to treat
pain and
fever. It is typically used for mild to moderate pain. It is typically used either by mouth or
rectally but is also available
intravenously. and is generally safe at recommended doses.
NSAIDs Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a
drug class that groups together
drugs that decrease pain and
lower fever, and, in higher doses, decrease
inflammation. The most prominent members of this group of drugs —
aspirin,
ibuprofen,
naproxen, and
diclofenac — are all available
over the counter in most countries.
COX-2 inhibitors These drugs have been derived from NSAIDs. The
cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least two 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,
celecoxib, 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 events 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.
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.
Tapentadol, 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 and
vomiting (generally relieved by a short course of
antiemetics such as
phenergan).
Pruritus (itching) may require switching to a different opioid.
Constipation occurs in almost all patients on opioids, and
laxatives (
lactulose,
macrogol-containing or co-danthramer) are typically co-prescribed. 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 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 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. Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and
alcohol use disorder. 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.
Combinations Analgesics are frequently used in combination, such as the
paracetamol and
codeine preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as
pseudoephedrine for
sinus-related preparations, or with
antihistamine drugs for people with allergies. 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, 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.
Alternative medicine 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.
Flupirtine 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.
Ziconotide, a blocker of potent
N-type voltage-gated calcium channels, is administered
intrathecally for the relief of severe, usually cancer-related pain.
Adjuvants 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,
promethazine,
carisoprodol, or
tripelennamine to increase the pain-killing ability of a given dose of opioid analgesic. Adjuvant analgesics, also called atypical analgesics, include
orphenadrine,
mexiletine,
pregabalin,
gabapentin,
cyclobenzaprine,
hyoscine (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.
Dextromethorphan 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
ketobemidone and perhaps
piritramide have intrinsic NMDA action. The
anticonvulsant carbamazepine is used to treat neuropathic pain. Similarly, the
gabapentinoids
gabapentin and
pregabalin are prescribed for neuropathic pain, and
phenibut is available without prescription. Gabapentinoids work as α2δ-subunit blockers of
voltage-gated calcium channels, and tend to have other mechanisms of action as well. Gabapentinoids are all
anticonvulsants, which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system.
Other uses 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
topically.
Lidocaine, an
anesthetic, and
steroids may be injected into joints for longer-term pain relief. Lidocaine is also used for painful
mouth sores 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. ==Uses==