Analgesic drugs

An analgesic (colloquially known as painkillers) is any member of the diverse group of drugs used to relieve pain and to achieve analgesia. This derives from Greek an-, "without", and -algia, "pain". Analgesic drugs act in various ways on the peripheral and central nervous system; they include paracetamol (acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others. Some other classes of drugs not normally considered analgesics are used to treat neuropathic pain syndromes; these include tricyclic antidepressants and anticonvulsants.

Stepwise use
In 1990, the World Health Organisation (WHO) approved an "analgesic ladder" which recommends the stepwise introduction of stronger painkillers if the more basic ones are ineffective. While originally introduced for managing pain in cancer, these guidelines have found application in all fields of medicine, such as surgery and anaesthetics.
 * 1) The first step is paracetamol (500 mg to 1 g every 4–6 hours).
 * 2) The second step involves the addition of an NSAID (e.g. ibuprofen) or a weak opioid (such as codeine).
 * 3) The third step comprises the addition of a strong opioid (such  as morphine, oxycodone or a fentanyl preparation); if codeine is being taken the strong opioid replaces codeine.

Paracetamol and NSAIDs
The exact mechanism of action of paracetamol is uncertain, but it appears to be acting centrally. Aspirin and the NSAIDs inhibit cyclooxygenase, leading to a decrease in prostaglandin production; this improves pain and also inflammation (in contrast to paracetamol and the opioids).

Paracetamol has few side effects, but dosing is limited by possible hepatotoxicity (potential for liver damage). NSAIDs may predispose to peptic ulcers, renal failure, allergic reactions, and hearing loss. They may also increase the risk of hemorrhage.

Opiates and morphinomimetics
Tramadol and buprenorphine are thought to be partial agonists of the opioid receptors. Morphine, the archetypical opioid, and various other substances (e.g. pethidine, oxycodone, hydrocodone, diamorphine) all exert a similar influence on the cerebral opioid system. Dosing may be limited by opioid toxicity (confusion, myoclonic jerks and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.

Opioids, while very effective analgesics, may have some unpleasant side-effects. Up to 1 in 3 patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics). 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 similar narcotic analgesics are safe and effective, carrying relatively little risk of addiction. Occasionally, gradual tapering of the dose is required to avoid withdrawal symptoms.

Specific agents
In patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic antidepressants, especially amitriptyline, have been shown to improve pain in what appears to be a central manner. The exact mechanism of carbamazepine, gabapentin and pregabalin is similarly unclear, but these anticonvulsants are used to treat neuropathic pain with modest success.

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 allergy sufferers.

Topical or systemic
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel; capsaicin also is used topically. Lidocaine and steroids may be injected into painful 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.

Psychotropic agents
Tetrahydrocannabinol and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic properties, although the use of cannabis derivatives is illegal in many countries. Other analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other α2-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues.

Addiction
In the United States in recent years, however, there has been a wave of new addictions to prescription painkillers such as oxycodone (OxyContin, Percocet etc.) and hydrocodone (Vicodin, Lortab etc.). The U.S. Government is now taking steps to reverse this epidemic, which it has blamed on easy access to prescription drugs over the Internet. The bigger problem however is doctors overprescribing these drugs.

Reference

 * Cancer pain relief and palliative care. Report of a WHO expert committee [World Health Organization Technical Report Series, 804] . Geneva, Switzerland: World Health Organization; 1990. pp. 1-75.

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