An opioid is a chemical substance that has a morphine-like action in the body. The main use is for pain relief. These agents work by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The receptors in these two organ systems mediate both the beneficial effects, and the undesirable side effects. There are a number of broad classes of opioids: Look up substance in Wiktionary, the free dictionary. ... This article is about the drug. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... To meet Wikipedias quality standards, this article may require cleanup. ... A diagram showing the CNS: 1. ... Gut redirects here. ... A side-effect is any effect other than an intended primary effect. ...

• natural opiates, alkaloids contained in the resin of the opium poppy including morphine, codeine and thebaine, but not papaverine and noscapine which have a different mechanism of action;
• morphines: include esters of morphine and morphine prodrugs, diacetylmorphine (Heroin), nicomorphine, dipropanoylmorphine, benzylmorphine and ethylmorphine;
• semi-synthetic opiates, created from the natural opioids, such as hydromorphone, hydrocodone, oxycodone, oxymorphone and desomorphine;
• fully synthetic opioids, such as fentanyl, pethidine, methadone, and propoxyphene;
• endogenous opioid peptides, produced naturally in the body, such as endorphins, enkephalins, dynorphins, and endomorphins.

Although the term opiate is often used as a synonym for opioid, it is more properly limited to the natural opium alkaloids and the semi-synthetics derived from them. An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and other animals. ... Binomial name L. The opium poppy, Papaver somniferum, is the type of poppy from which opium and all refined opiates such as morphine, thebaine, codeine, papaverine, and noscapine are extracted. ... This article is about the drug. ... For the band, see Codeine (band). ... A minor constituent of opium, thebaine or paramorphine (C19H21NO3) is chemically similar to both morphine and codeine, but produces stimulatory rather than depressant effects. ... Papaverine is an opium alkaloid used primarily in the treatment of visceral spasm, vasospasm (especially those involving the heart and the brain), and occasionally in the treatment of erectile dysfunction. ... Noscapine (also known as Narcotine) is an opioid agonist without significant analgesic properties [1]. It is grouped as part of the benzylisoquinolines, of which papaverine is also included. ... Diacetylmorphine (INN), diamorphine (BAN), or more commonly heroin, is a semi-synthetic opioid. ... Nicomorphine (Vilan) is the 3,6-dinicotinate ester of morphine. ... Dipropanoylmorphine is the 3,6-dipropanoyl ester of morphine, CAS number 10589-79-4. ... This article needs additional references or sources to facilitate its verification. ... Ethylmorphine is a drug in the class of both opiates (representing a minor synthetic change from morphine) and opioids (being effective in the CNSs opioid reception system) . Its effects in humans mainly stem from its metabolic conversion to morphine. ... Hydromorphone is a drug developed in Germany in the 1920s and introduced to the mass market beginning in 1926. ... Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... Not to be confused with oxytocin. ... Oxymorphone (Opana, Numorphan) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic that is derived from thebaine, and is approximately 6–8 times more potent than morphine. ... Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica (Belgium) in the late 1950s, with a potency many times that of morphine. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland);[1] Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ... Methadone (Dolophine, Amidone, Methadose, Physeptone, Heptadon and many others) is a synthetic opioid, used medically as an analgesic, antitussive and a maintenance anti-addictive for use in patients on opioids. ... Dextropropoxyphene is an analgesic in the opioid category that is used to treat severe pain and severe coughs. ... Look up Endogenous in Wiktionary, the free dictionary. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... For other uses, see Endorphin (disambiguation). ... Endorphins are endogenous opioid biochemical compounds. ... Dynorphin (Dyn) is a popular and powerful opioid ligand. ... Runners high redirects here. ... For other uses see Opiate (disambiguation), or for the class of drugs see Opioid. ...

Amongst analgesics are a small number of agents which act on the central nervous system but not on the opioid receptor system and therefore have none of the other (narcotic) qualities of opioids although they may produce euphoria by relieving pain -- a euphoria that, because of the way it is produced, does not form the basis of morbid seek orientation, habituation, physical dependence, or addiction. Foremost amongst these are nefopam, orphenadrine, and perhaps phenyltoloxamine and/or some other antihistamines. The remainder of analgesics work peripherally. Research is starting to show that morphine and related drugs may indeed have peripheral effects as well, such as morphine gel working on burns, but peripherally-acting analgesics include aspirin, ibuprofen and the like. Paracetamol is predominantly a centrally acting analgesic (non-narcotic) which mediates its effect by action on descending serotonergic (5-hydroxy triptaminergic) pathways, to increase 5-HT release (which inhibits release of pain mediators). It also decreases cyclo-oxygenase activity. Categories: Possible copyright violations ... Orphenadrine (Norflex®, Disipal®, Banflex®, Flexon® and others) is an anticholinergic and NMDA receptor antagonist [1]drug belonging to the ethanolamine class of antihistamines. ... Phenyltoloxamine is an antihistamine with sedative and analgesic effects. ... An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. ...

Many of the alkaloids and other derivatives of the opium poppy are not opioids or narcotics; the best example is the smooth-muscle relaxant papaverine. Noscapine is a marginal case as it does have CNS effects but not necessarily similar to morphine, and it is probably in a category all its own. Dextromethorphan (the stereoisomer of levomethorphan, a semi-synthetic opioid agonist) and it's metabolite dextrorphan have no opioid agonist effects at all despite their structure similarity to other opioids, instead they are potent NMDA antagonists and sigma 1 and 2 agonists and are used in many over-the-counter cough suppressants. Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug found in many over-the-counter cold and cough medicines. ... Levomethorphan is an optical isomer of dextromethorphan. ... Dextrorphan is a pharmacologically active metabolite of Dextromethorphan (DXM). ... NMDA (N-methyl-D-aspartic acid) is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor. ... For other uses, see Sigma (disambiguation). ... Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ...

Pharmacology

Main article: opioid receptor

Opioids bind to specific opioid receptors in the central nervous system and in other tissues. There are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Alternatively, σ (Sigma) receptors are no longer considered to be opioid receptors because: they are not reversed by the opioid inverse-agonist naloxone, they do not exhibit high-affinity binding for ketamine and phencyclidine, and they are stereoselective for dextro-rotatory isomers while the other opioid receptors are stereo-selective for laevo-rotatory isomers. In addition, there are three subtypes of μ receptor: μ₁ and μ₂, and the newly discovered μ₃. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all G-protein coupled receptors acting on GABAergic neurotransmission. The pharmacodynamic response to an opioid depends on which receptor it binds, its affinity for that receptor, and whether the opioid is an agonist or an antagonist. For example, the supraspinal analgesic properties of the opioid agonist morphine are mediated by activation of the μ₁ receptor, respiratory depression and physical dependence (dependency) by the μ₂ receptor, and sedation and spinal analgesia by the κ receptor. Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ₁ and μ₂ for example) providing even more [measurably] specific responses. Unique to each opioid is their distinct binding affinity to the group(s) of opioid receptors (eg. the μ, κ, and δ opioid receptors are activated at different magnitudes according to the specific receptor binding affinities of the opioid, such as the μ opioid receptor effects being the primary receptor response to the opioid morphine, or the κ opioid receptor residing as the primary binding receptor to ketazocine). It is this primary mechanism that allows for such a wide class of opioids and molecular designs to exist, as well as their composition of slightly differing effects and side-effects, all related to their individual molecular structure/makeup (which itself is responsible for duration of action, whereby metabolic-breakdown is the primary method of opioid duration)^[1]. To meet Wikipedias quality standards, this article may require cleanup. ... To meet Wikipedias quality standards, this article may require cleanup. ... A diagram showing the CNS: 1. ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... κ-Opioid receptors are involved with analgesia, but activation also produces marked nausea and dysphoria. ... δ-Opioid receptor activation produces analgesia. ... Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. ... Dextrorotation is the property of rotating plane polarized light clockwise. ... In chemistry, isomers are molecules with the same chemical formula and often with the same kinds of bonds between atoms, but in which the atoms are arranged differently. ... Laevorotation is the property of rotating plane polarized light to the left (in contrast to glucose which is dextrorotatory--to the right). ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... In cell biology, G-protein-coupled receptors, also known as GPCR, seven transmembrane receptors, heptahelical receptors, or 7TM receptors, are a class of transmembrane receptors. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell. ... Pharmacodynamics is the study of the biochemical and physiological effects of drugs and the mechanisms of drug action and the relationship between drug concentration and effect. ... Agonists In pharmacology an agonist is a substance that binds to a specific receptor and triggers a response in the cell. ... Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling. ... Supraspinal means above the spine, and may refer to: brain or other supraspinal structures: supraspinous ligament supraspinous muscle supraspinatous fossa Category: ... This article is about the drug. ... Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... This article is about the drug. ...

Uses

Clinical use

Opioids have long been used to treat acute pain (such as post-operative pain). They have also been found to be invaluable in palliative care to alleviate the severe, chronic, disabling pain of terminal conditions such as cancer. Contrary to popular belief, high doses are not required to control the pain of advanced or end-stage disease, with the median dose in such patients being only 15mg oral morphine every four hours (90mg/24 hours), i.e. 50% of patients manage on lower doses, and requirements can level off for many months at a time despite the fact that opioids have some of the greatest potential for tolerance of any category of drugs. Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...

In recent years there has been an increased use of opioids in the management of non-malignant chronic pain. This practice has grown from over 30 years experience in palliative care of long-term use of strong opioids which has shown that addiction is rare when the drug is being used for pain relief. The basis for the occurrence of iatrogenic addiction to opioids in this setting being several orders of magnitude lower than the general population is the result of a combination of factors. Open and voluminous communication and meticulous documentation amongst patient, any caretakers, physicians, and chemists (pharmacists) is one part of this; the aggressive and consistent use of opioid rotation, adjuvant analgesics, potentiators, and drugs which deal with other elements of the pain (NSAIDS) and opioid side effects (stimulants in some cases, antihistamines) both improve the prognosis for the patient and appear to contribute to the rarity of addiction in these cases. Chronic pain was originally defined as pain that has lasted 6 months or longer. ...

The use of some opioids against depression, especially as a short-term or one-time treatment in cases of severe point-source temporary exacerbation depression or the failure of coping mechanisms in non-depressed people has been "rediscovered" in the English-speaking world in the last eight years or so although this was a common indication for some of the milder narcotic preparations prior to the Harrison Narcotic Act of 1914. A quick Google search on any day shows the following:

• Drugs found to have the most marked antidepressant effects include buprenorphine, butorphanol, tramadol (which also works directly in the serotonin and norepinephrine systems in the body), dihydrocodeine, and even oxycodone. In theory, levorphanol, dromoran, ketobemidone and its relatives as well as dextromoramide should have the same general effects.
• In previous centuries, laudanum and other whole-opium products were most used for this purpose.
• Mixtures of tricyclic antidepressants and compatible opioids are greater than the sum of their parts for both analgesia and mood elevation and sedation.
• Orphenadrine, cyclobenzaprine, cocaine, ephedrine, caffeine, scopolamine and other drugs sometimes employed as adjuncts as in the proprietary drug Trivalin, which in 1920 was a combination of the valerate salts of morphine, cocaine, and caffeine. A herbal preparation for use as a relatively mild sleep aid by this same name on the market now is in no way related to the Trivalin of decades past.
• Scopolamine by itself is also being tested for use as an antidepressant.
• Scopolamine also has useful benzodiazepine-like effects without the potential for physical dependence &c.
• The alkylamine antihistamines, especially dexclorpheniramine and chlorpheniramine work on the same principle and extended-release dexchlorpheniramine, known in most of the world as Polaramine is the most used at this time of the agents listed above for treatment of the aforementioned subset of psychological problems.

Buprenorphine, is an opioid drug with partial agonist and antagonist actions. ... Butorphanol (INN) is a morphinan-type synthetic opioid analgesic marketed in the U.S. under the trade name Stadol. ... Tramadol (INN) (IPA: ) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. ... For the professional wrestling stable, see Ravens Nest#Serotonin. ... Norepinephrine (INN)(abbr. ... Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid... Not to be confused with oxytocin. ... Levorphanol is an opioid medication used to treat severe pain. ... A potent, easily synthesized opioid often used as a substitute for morphine or a stronger opioid (such as fentanyl) when used in illegal drugs. ... Ketobemidone structure Ketobemidone is a powerful opioid analgesic. ... Dextromoramide (Palfium®, Palphium®, Jetrium®, Dimorlin®) is the right-handed isomer of the moramide molecule. ... Chemical structure of the tricyclic antidepressant amitriptyline Tricyclic antidepressants are a class of antidepressant drugs first used in the 1950s. ... Orphenadrine (Norflex®, Disipal®, Banflex®, Flexon® and others) is an anticholinergic and NMDA receptor antagonist [1]drug belonging to the ethanolamine class of antihistamines. ... Cyclobenzaprine is a skeletal muscle relaxant and a central nervous system (CNS) depressant. ... For other uses, see Cocaine (disambiguation). ... Ephedrine (EPH) is a sympathomimetic amine similar in structure to the synthetic derivatives amphetamine and methamphetamine. ... For other uses, see Caffeine (disambiguation). ... Scopolamine, also known as hyoscine, is a tropane alkaloid drug obtained from plants of the family Solanaceae (nightshades), such as henbane or jimson weed (Datura species). ... This article is about the drug. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , often abbreviated to benzos) are a class of sedative hypnotic psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. ... Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed as its salt chlorphenamine maleate (CPM), is first-generation antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. ...

United States

The sole clinical indications for opioids in the United States, according to Drug Facts and Comparisons, 2005, are

• Analgesia and anesthesia
• Cough (codeine and hydrocodone only)
• Diarrhea (generally loperamide or diphenoxylate, but laudanum or morphine may be used in some cases of severe diarrheal diseases)
• Anxiety due to shortness of breath (oxymorphone only)
• Detoxification (methadone and buprenorphine only)

In the U.S., doctors virtually never prescribe opioids for psychological relief (with the narrow exception of anxiety due to shortness of breath), despite their extensively reported psychological benefits. There are virtually no exceptions to this practice, even in circumstances where researchers have reported opioids to be especially effective and where the possibility of addiction or diversion is very low—for example, in the treatment of senile dementia, geriatric depression, and psychological distress due to chemotherapy or terminal diagnosis (see Abse; Berridge; Bodkin; Callaway; Emrich; Gold; Gutstein; Mongan; Portenoy; Reynolds; Takano; Verebey; Walsh; Way). For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Anesthesia or anaesthesia (see spelling differences) has traditionally meant the condition of having the perception of pain and other sensations blocked. ... Imodium redirects here. ... On opiod agonist used for the treatment of diarrhea. ... This article is about the medicine. ... Dyspnea (Latin dyspnoea, Greek dyspnoia from dyspnoos - short of breath) or shortness of breath (SOB) is perceived difficulty breathing or pain on breathing. ... Oxymorphone (Opana, Numorphan) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic that is derived from thebaine, and is approximately 6–8 times more potent than morphine. ... Buprenorphine, is an opioid drug with partial agonist and antagonist actions. ...

Use of opioids in palliative care

The current key text for palliative care is the Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle, D., Hanks, G., Cherney, I., and Calman, K., eds., Oxford University Press, 2004). This states that the indications for opioid administration in palliative care are:

• "Any pain of moderate or greater severity, irrespective of the underlying pathophysiological mechanism." (p.327)
• Breathlessness / shortness of breath: the largest evidence base exists for morphine. Several mechanisms are suggested for its action on breathlessness (p.605–7).
• Diarrhea: codeine and loperamide are the most widely used opioid for this problem. Loperamide has the advantage of acting only on the gut, since very little is absorbed (p.493).
• Painful wounds: topical morphine in an aqueous gel can be an effective agent (p.392). Their use is based on the discovery of activated opioid receptors in damaged tissue.

Not just opioids... Dyspnea (Latin dyspnoea, Greek dyspnoia from dyspnoos - short of breath) or shortness of breath (SOB) is perceived difficulty breathing or pain on breathing. ...

In palliative care opioids are always used in combination with adjuvant analgesics (drugs which have an indirect effect on the pain), and as an integral part of care of the whole person.

Contraindications for opioids

In palliative care, opioids are not recommended for sedation or anxiety because experience has found them to be ineffective agents in these roles. Some opioids are relatively contraindicated in renal failure because of the accumulation of the parent drug or their active metabolites (e.g. morphine and oxycodone). Age (young or old) is not a contraindication to strong opioids. Some synthetic opioids such as pethidine have metabolites which are actually neurotoxic and should therefore be used only in acute situations. Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland);[1] Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ...

History

Non-clinical use was criminalized in the U.S by the Harrison Narcotics Tax Act of 1914, and by other laws worldwide. Since then, nearly all non-clinical use of opioids has been rated zero on the scale of approval of nearly every social institution. However, in United Kingdom the 1926 report of the Departmental Committee on Morphine and Heroin Addiction under the Chairmanship of the President of the Royal College of Physicians reasserted medical control and established the "British system" of control—which lasted until the 1960s; in the U.S. the Controlled Substances Act of 1970 markedly relaxed the harshness of the Harrison Act. The Harrison Narcotics Tax Act was an American law that regulated and taxed the production, importation, distribution and use of opiates. ... This box:      The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ...

Before the twentieth century, institutional approval was often higher, even in Europe and America. In some cultures, approval of opioids was significantly higher than approval of alcohol.

Global shortage of poppy-based medicines

Morphine and other poppy-based medicines have been identified by the World Health Organization as essential in the treatment of severe pain. However, only six countries use 77% of the world's morphine supplies, leaving many emerging countries lacking in pain relief medication.^[2]. The current system of supply of raw poppy materials to make poppy-based medicines is regulated by the International Narcotics Control Board under the provision of the 1961 Single Convention on Narcotic Drugs. The amount of raw poppy materials that each country can demand annually based on these provisions must correspond to an estimate of the country's needs taken from the national consumption within the preceding two years. In many countries, underprescription of morphine is rampant because of the high prices and the lack of training in the prescription of poppy-based drugs. The World Health Organisation is now working with different countries' national administrations to train healthworkers and to develop national regulations regarding drug prescription in order to facilitate a greater prescription of poppy-based medicines.^[3] Mr. ... Single Convention on Narcotic Drugs Opened for signature March 30, 1961 at New York Entered into force December 13, 1964[1] Conditions for entry into force 40 ratifications Parties 180[2] The Single Convention on Narcotic Drugs is the international treaty against illicit drug manufacture and trafficking that forms the... For other meanings of the acronym WHO, see WHO (disambiguation) WHO flag Headquartered in Geneva, Switzerland, the World Health Organization (WHO) is an agency of the United Nations, acting as a coordinating authority on international public health. ...

Another idea to increase morphine availability is proposed by the Senlis Council, who suggest, through their proposal for Afghan Morphine, that Afghanistan could provide cheap pain relief solutions to emerging countries as part of a second-tier system of supply that would complement the current INCB regulated system by maintaining the balance and closed system that it establishes while providing finished product morphine to those suffering from severe pain and unable to access poppy-based drugs under the current system. The Senlis Council is an international policy think tank with offices in Kabul, London, Paris and Brussels. ... Afghan morphine or Poppy for Medicine is an alternative development solution put forward to combat the poverty and public disenchantment caused by international counter-narcotics eradication policies in Afghanistan. ... Mr. ...

Adverse effects

For more information see^[4] and the online palliative care formulary (available on Palliativedrugs.com).

Common adverse reactions in patients taking opioids for pain relief:

These include: nausea and vomiting, drowsiness, dry mouth, miosis, and constipation. Fortunately, most of these are not a problem (see Treating Opioid Adverse Effects below). Miosis should not be confused with meiosis, the cellular division process involved in sexual reproduction. ...

Infrequent adverse reactions in patient taking opioids for pain relief:

These include: dose-related respiratory depression (see below), confusion, hallucinations, delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness, headache, urinary retention, ureteric or biliary spasm, muscle rigidity, myoclonus (with high doses), and flushing (due to histamine release, except fentanyl and remifentanil). This article is about the mental state and medical condition. ... Hypothermia is a condition in which an organisms temperature drops below that Required fOr normal metabolism and Bodily functionS. In warm-blooded animals, core [[body Temperature]] is maintained nEar a constant leVel through biologic [[homEostasis]]. But wheN the body iS exposed to cold Its internal mechanismS may be unable... Bradycardia, as applied to adult medicine, is defined as a resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. ... This article or section does not cite any references or sources. ... Orthostatic hypotension (also known as postural hypotension, orthostatic intolerance and, colloquially, as head rush or a dizzy spell) is a sudden fall in blood pressure, typically greater than 20/10 mm Hg, that occurs when a person assumes a standing position, usually after a prolonged period of rest. ...

Other adverse effects:

Opioid-induced hyperalgesia has been observed in some patients, whereby individuals using opioids to relieve pain may paradoxically experience more pain as a result of their medication. This phenomenon, although uncommon, is seen in some palliative care patients, most often when dose is escalated rapidly. ^{[5] [6]} If encountered, rotation between several different opioid analgesics may mitigate the development of hyperalgesia. ^{[7] [8]} Opioid-induced hyperalgesia[1] or opioid-induced abnormal pain sensitivity[2] is a phenomenon associated with the long term use of opioids such as morphine, hydrocodone, oxycodone, and methadone. ... Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ...

Both therapeutic and chronic use of opioids can compromise the function of the immune system. Opioids decrease the proliferation of macrophage progenitor cells and lymphocytes, and affect cell differentiation (Roy & Loh, 1996). Opioids may also inhibit leukocyte migration. However the relevance of this in the context of pain relief is not known. A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, from makros large + phagein eat) are cells within the tissues that originate from specific white blood cells called monocytes. ... A scanning electron microscope (SEM) image of a single human lymphocyte. ... White Blood Cells is also the name of a White Stripes album. ...

Treating opioid adverse effects

Most adverse effects can be managed successfully. (For more complete information see ^[9] and the online palliative care formulary available on Palliativedrugs.com.)

Nausea: tolerance occurs within 7–10 days, during which antiemetics (e.g. low dose haloperidol 1.5–3mg once at night) are very effective. Stronger antiemetics such as ondansetron or tropisetron may be indicated if nausea is severe or continues for an extended period, although these tend to be avoided due to their high cost unless nausea is really problematic. For other uses, see Nausea (disambiguation). ... Haloperidol (sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol, Halosten, Keselan, Linton, Peluces, Serenace, Serenase, Sigaperidol) is a conventional, or typical, butyrophenone antipsychotic drug. ... Ondansetron (INN) (IPA: ) is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. ... Tropisetron (INN) is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia. ...

Vomiting: if this is due to gastric stasis (large volume vomiting, brief nausea relieved by vomiting, oesophageal reflux, epigastric fullness, early satiation) then this can be managed with a prokinetic (e.g. domperidone or metoclopramide 10mg every eight hours), but usually needs to be started by a non-oral route (e.g. subcutaneous for metoclopramide, rectally for domperidone). Heaving redirects here. ... Domperidone (trade name Motilium or Motillium) is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting. ... Metoclopramide (INN) (IPA: ) is a potent dopamine receptor antagonist used for its antiemetic and prokinetic properties. ...

Drowsiness: tolerance usually develops over 5–7 days, but if troublesome, switching to an alternative opioid often helps. Certain opioids such as fentanyl tend to be particularly sedating, while others such as oxycodone and meperidine (pethidine) tend to produce less sedation, but individual patients responses can vary markedly and some degree of trial and error may be needed to find the most suitable drug for a particular patient. Somnolence (or drowsiness, or hypersomnia) is a state of near-sleep, a strong desire for sleep, or sleeping unusually long periods. ... Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica (Belgium) in the late 1950s, with a potency many times that of morphine. ... Not to be confused with oxytocin. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; operidine; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ...

Itching: tends not to be a severe problem when opioids are used for pain relief, but if required then antihistamines are useful for counteracting itching. Non-sedating antihistamines such as fexofenadine are preferable so as to avoid increasing opioid induced drowsiness, although some sedating antihistamines such as orphenadrine may be helpful as they produce a synergistic analgesic effect which allows smaller doses of opioids to be used while still producing effective analgesia. For this reason some opioid/antihistamine combination products have been marketed, such as Meprozine (meperidine/promethazine) and Diconal (dipipanone/cyclizine), which may also have the added advantage of reducing nausea as well. An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... An H1 antihistamine is a histamine antagonist which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the H1 receptor. ... Fexofenadine hydrochloride (brand names include Allegra® and Telfast®) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. ... Orphenadrine (Norflex®, Disipal®, Banflex®, Flexon® and others) is an anticholinergic and NMDA receptor antagonist [1]drug belonging to the ethanolamine class of antihistamines. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; operidine; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ... Promethazine is a first-generation H1 receptor antagonist antihistamine and antiemetic medication. ... Dipipanone hydrochloride is an opioid painkiller. ... Cyclizine is an antihistamine drug used to treat nausea, vomiting and dizziness associated with motion sickness, vertigo and post-operative following administration of general anaesthesia and opioids. ...

Constipation: this develops in 99% of patients on opioids and since tolerance to this problem does not develop, nearly all patients on opioids will need a laxative. Over 30 years experience in palliative care has shown that most opioid constipation can be successfully prevented: "Constipation ... is treated [with laxatives and stool-softeners]" (Burton 2004, 277). According to Abse, "It is very important to watch out for constipation, which can be severe” and “can be a very considerable complication” (Abse 1982, 129) if it is ignored. Peripherally acting opioid antagonists such as alvimopan and methylnaltrexone (Relistor) are currently under development which have been found to effectively relieve opioid induced constipation without affecting analgesia or triggering withdrawal symptoms.^[10][11] Constipation, costiveness, or irregularity, is a condition of the digestive system where a person (or animal) experiences hard feces that are difficult to egest. ... Alvimopan (Entereg) is a drug which behaves as a peripherally acting μ-opioid antagonist. ... Methylnaltrexone (MTNX) is one of the newer agents of peripherally-acting μ-opioid antagonists that act to reverse some of the side effects of opioid drugs such as constipation without affecting analgesia or precipitating withdrawals. ...

Respiratory depression: Although this is the most serious adverse reaction associated with opioid use it usually is seen with the use of a single, intravenous dose in an opioid-naive patient. In patients taking opioids regularly for pain relief, tolerance to respiratory depression occurs rapidly, so that it is not a clinical problem. Several drugs have been developed which can block respiratory depression completely even from high doses of potent opioids, without affecting analgesia, although the only respiratory stimulant currently approved for this purpose is doxapram, which has only limited efficacy in this application.^[12][13] Newer drugs such as BIMU-8 and CX-546 may however be much more effective.^[14][15][16] In medicine, hypoventilation exists when ventilation is inadequate to perform gas exchange. ... Doxapram hydrochloride (marketed as Dopram®) is an analeptic agent (a stimulant of the central nervous system). ...

Reversing the effect of opioids: Opioid effects can be rapidly reversed with an opioid antagonist (literally an inverse agonist) such as naloxone or naltrexone. These competitive antagonists bind to the opioid receptors with higher affinity than agonists but do not activate the receptors. This displaces the agonist, attenuating and/or reversing the agonist effects. However, the elimination half-life of naloxone can be shorter than that of the opioid itself, so repeat dosing or continuous infusion may be required, or a longer acting antagonist such as nalmefene may be used. In patients taking opioids regularly it is essential that the opioid is only partially reversed to avoid a severe and distressing reaction of waking in excruciating pain. This is achieved by not giving a full dose (e.g. naloxone 400 μg) but giving this in small doses (e.g. naloxone 40 μg) until the respiratory rate has improved. An infusion is then started to keep the reversal at that level, while maintaining pain relief. Naloxone is a drug used to counter the effects of overdosing on opioids such as heroin and morphine. ... In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ... Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. ... Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. ... A competitive antagonist is a receptor antagonist which binds to a receptor but fails to activate it. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Nalmefene (Revex) is an opioid receptor antagonist used primarily in the management of alcohol dependence, and also has been investigated for the treatment of other addictions such as pathological gambling and addiction to shopping. ...

How safe are opioids? A world view

There are a number of paradoxical beliefs about opioids:

• 33% of UK doctors believe they had possibly shortened life during alleviation of symptoms,^[17] and yet a follow-up study showed that UK doctors are particularly cautious about shortening life.^[18]
• There is a belief that the use of opioids in pain is a fine balance between relief and hastening death, and yet palliative care physicians do not find themselves faced with the dilemma of relieving symptoms at the risk of shortening life.^[19]
• The Dutch public equate high dose morphine and sedation with euthanasia,^[20] and yet it is the least used class of drug used for euthanasia in the Netherlands.

However, studies around the globe over the past 20 years have repeatedly shown opioids to be safe when they are used correctly. In the UK two studies have shown that double doses of bedtime morphine did not increase overnight deaths,^[21] and that sedative dose increases were not associated with shortened survival (n=237).^[22] Another UK study showed that the respiratory rate was not changed by morphine given for breathlessness to patients with poor respiratory function (n=15).^[23] In Australia, no link was found between doses of opioids, benzodiazepines or haloperidol and survival.^[24] In Taiwan, a study showed that giving morphine to treat breathlessness on admission and in the last 48 hours did not affect survival.^[25] The survival of Japanese patients on high dose opioids and sedatives in the last 48 hours was the same as those not on such drugs.^[26] In U.S. patients whose ventilators were being withdrawn, opioids did not speed death, while benzodiazepines resulted in longer survival (n=75).^[27] Morphine given to elderly patients in Switzerland for breathlessness showed no effect on respiratory function (n=9, randomised controlled trial).^[28] Injections of morphine given subcutaneously to Canadian patients with restrictive respiratory failure did not change their respiratory rate, respiratory effort, arterial oxygen level, or end-tidal carbon dioxide levels.^[29] Even when opioids are given intravenously, respiratory depression is not seen.^[30] For mercy killings not performed on humans, see Animal euthanasia. ...

Using opioids safely

• Starting doses: a person who has never been on analgesics would be started on oral morphine 2.5–5mg every four hours (or morphine by injection 1–2.5mg every four hours). Higher doses can be used if the patient was already on weaker analgesics.

• Titration: this describes the adjustment of a drug dose to a patient, while allowing the patient’s body time to adjust to the drug to minimise adverse effects. Titration is done in 25–50% steps every 1–2 days.

• Safety margin of opioids: morphine and diamorphine have a wide safety margin or "therapeutic range".

• Dose range: this is very wide but usually lies between 30–500mg per 24 hours of oral morphine, but with a median of 90mg (or 15mg every four hours). It is impossible to tell which patients need low doses and which need high doses, so all have to be started on low doses, unless changing from another strong opioid.^[31]

Double effect

The principle of double effect is not used in palliative care. Doctors are not faced with the dilemma of giving a potentially lethal drug dose to a distressed patient.^[32] The doctrine of double effect (DDE) is a thesis in ethics, usually attributed to Aquinas. ...

A palliative care doctor gives repeated, small doses of one or more drugs, each titrated to an individual until the symptoms are eased, while doing everything possible to avoid toxicity. Doctors who give 30–60 times the required dose of morphine or diamorphine, usually as a single intravenous dose, are acting either negligently or maliciously.^{[citation needed]} Since drug records should exist for opioids, there is a clear audit trail to follow if a subsequent investigation is required.

With exceptions such as Shipman, UK doctors are very cautious about shortening life.^[33] The persistent belief that opioids and sedatives shorten life or hasten death stems from the experiences of bad practice in the use of the drugs. Evidence in the last 20 years has shown that opioids and sedatives are safe when following palliative care protocols.^[31] Clinicians who believe otherwise should be challenged to provide robust clinical evidence to support their view.

Tolerance

Tolerance is the process whereby neuroadaptation occurs (through receptor desensitization) resulting in reduced drug effects. Tolerance is more pronounced for some effects than for others - tolerance occurs quickly to the effects on mood, itching, urinary retention, and respiratory depression, but occurs more slowly to the analgesia and other physical side effects. Drug tolerance occurs when a subjects reaction to a drug (such as a painkiller or intoxicant) decreases so that larger doses are required to achieve the same effect. ...

Tolerance to opioids is attenuated by a number of substances, including calcium channel blockers^[34][35], intrathecal magnesium^[36] and zinc^[37], and NMDA antagonists such as ketamine.^[38] The cholecystokinin antagonist proglumide is also used to reduce tolerance to opioid drugs,^[39][40][41] and newer agents such as the phosphodiesterase inhibitor ibudilast have also been researched for this application.^[42] Calcium channel blockers are a class of drugs and natural substances with effects on many excitable cells of the body, like the muscle of the heart, smooth muscles of the vessels or neuron cells. ... Intrathecal: Delivered into the spinal canal (intrathecal space surrounding the spinal cord), as in a spinal anaesthesia. ... General Name, symbol, number magnesium, Mg, 12 Chemical series alkaline earth metals Group, period, block 2, 3, s Appearance silvery white solid at room temp Standard atomic weight 24. ... General Name, symbol, number zinc, Zn, 30 Chemical series transition metals Group, period, block 12, 4, d Appearance bluish pale gray Standard atomic weight 65. ... Ketamine, one of the most common NMDA receptor antagonists. ... Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). ... A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). ... Ibudilast (AV-411) is an antiinflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE-4 subtype to the greatest extent,[1] but also showing significant inhibition of other PDE subtypes. ...

Magnesium and zinc deficiency speed up the development of tolerance to opioids^{[citation needed]} and relative deficiency of these minerals is quite common^[43] due to low magnesium/zinc content in food and use of substances which deplete them including diuretics (such as alcohol, caffeine/theophylline) and smoking. Reducing intake of these substances and taking zinc/magnesium supplements may slow the development of tolerance to opiates.^{[citation needed]}

Dependence

Dependence is characterised by extremely unpleasant withdrawal symptoms that occur if opioid use is abruptly discontinued after tolerance has developed. The withdrawal symptoms include severe dysphoria, sweating, nausea, rhinorrea, depression, severe fatigue, vomiting and pain. Slowly reducing the intake of opioids over days and weeks will reduce or eliminate the withdrawal symptoms.^[44] The speed and severity of withdrawal depends on the half-life of the opioid — heroin and morphine withdrawal occur more quickly and are more severe than methadone withdrawal, but methadone withdrawal takes longer. The acute withdrawal phase is often followed by a protracted phase of depression and insomnia that can last for months. The symptoms of opioid withdrawal can also be treated with other medications, but with a low efficacy. ^[45] Dependence also occurs for most other drugs, including caffeine and alcohol. Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... Look up dysphoria in Wiktionary, the free dictionary. ... Perspiration (also called sweating or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... For other uses, see Nausea (disambiguation). ... Heaving redirects here. ... Look up Pain in Wiktionary, the free dictionary. ... Methadone (Dolophine, Amidone, Methadose, Physeptone, Heptadon and many others) is a synthetic opioid, used medically as an analgesic, antitussive and a maintenance anti-addictive for use in patients on opioids. ... For other uses, see Caffeine (disambiguation). ... This article does not cite any references or sources. ...

Addiction

Addiction is the process whereby physical and/or psychological addiction develops to a drug - including opioids. The withdrawal symptoms can reinforce the addiction, driving the user to continue taking the drug. Psychological addiction is more common in people taking opioids recreationally, it is rare in patients taking opioids for pain relief.^[46] Several drugs have been shown to effectively block addiction to opioid drugs, most notably the plant extract ibogaine^[47] and its newer derivative 18-Methoxycoronaridine.^[48] Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... Ibogaine is an indole alkaloid, a long-acting hallucinogen which has gained attention due to its application in the treatment of opioid addiction and similar addiction syndromes. ... 18-methoxycoronaridine. ...

Abuse

Drug abuse is the misuse of drugs producing negative consequences. Comparison of the perceived harm for various psychoactive drugs from a poll among medical psychiatrists specialized in addiction treatment[1] This article is an overview of the nontherapeutic use of alcohol and drugs of abuse. ...

Examples of opioids

Endogenous opioids

Dunniod-peptides that are produced in the body include: Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ...

• Endorphins
• Enkephalins
• Dynorphins
• Endomorphins

β-endorphin is expressed in Pro-opiomelanocortin (POMC) cells in the arcuate nucleus and in a small population of neurons in the brainstem, and acts through μ-opioid receptors. β-endorphin has many effects, including on sexual behavior and appetite. β-endorphin is also secreted into the circulation from pituitary corticotropes and melanotropes. α-neoendorphin is also expressed in POMC cells in the arcuate nucleus. For other uses, see Endorphin (disambiguation). ... Endorphins are endogenous opioid biochemical compounds. ... Dynorphin (Dyn) is a popular and powerful opioid ligand. ... Runners high redirects here. ... Beta-endorphin is a neurotransmitter which is released from the anterior pituitary gland. ... Pro-opiomelanocortin (POMC) is a precursor polypeptide that is built of 241 amino acid residues. ... The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. ... The brain stem is the stalk of the brain below the cerebral hemispheres. ... Sexual behavior is a form of physical intimacy that may be directed to reproduction (one possible goal of sexual intercourse) and/or to the enjoyment of activity involving sexual gratification. ... The appetite is the desire to eat food, felt as hunger. ... Corticotropes (or corticotrophs) are cells in the anterior pituitary which produce adrenocorticotrophic hormone and melanocyte stimulating hormone. ...

[met]-enkephalin is widely distributed in the CNS; [met]-enkephalin is a product of the proenkephalin gene, and acts through μ and δ-opioid receptors. [leu]-enkephalin, also a product of the proenkephalin gene, acts through δ-opioid receptors. Endorphins are endogenous opioid biochemical compounds. ... Endorphins are endogenous opioid biochemical compounds. ...

Dynorphin acts through κ-opioid receptors, and is widely distributed in the CNS, including in the spinal cord and hypothalamus, including in particular the arcuate nucleus and in both oxytocin and vasopressin neurons in the supraoptic nucleus. Dynorphin (Dyn) is a popular and powerful opioid ligand. ... The Spinal cord nested in the vertebral column. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. ... Oxytocin (Greek: quick birth) is a mammalian hormone that also acts as a neurotransmitter in the brain. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Arginine vasopressin (AVP), also known as vasopressin, argipressin or antidiuretic hormone (ADH), is a hormone found in most mammals, including humans. ... The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. ...

Endomorphin acts through μ-opioid receptors, and is more potent than other endogenous opioids at these receptors. Runners high redirects here. ...

Opium alkaloids

Phenanthrenes naturally occurring in opium: Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings--as the above formula shows. ... This article is about the drug. ...

• Codeine
• Morphine
• Thebaine
• Oripavine^[49]

Preparations of mixed opium alkaloids, including papaveretum, are still occasionally used. For the band, see Codeine (band). ... This article is about the drug. ... A minor constituent of opium, thebaine or paramorphine (C19H21NO3) is chemically similar to both morphine and codeine, but produces stimulatory rather than depressant effects. ... Oripavine is an opiate and the major metabolite of thebaine. ... Papaveretum (BAN) is a preparation containing a mixture of hydrochloride salts of opium alkaloids. ...

Semisynthetic derivatives

• Diacetylmorphine (heroin)
• Dihydrocodeine
• Hydrocodone
• Hydromorphone
• Nicomorphine
• Oxycodone
• Oxymorphone

Diacetylmorphine (INN), diamorphine (BAN), or more commonly heroin, is a semi-synthetic opioid. ... Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid... Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... Hydromorphone is a drug developed in Germany in the 1920s and introduced to the mass market beginning in 1926. ... Nicomorphine (Vilan) is the 3,6-dinicotinate ester of morphine. ... Not to be confused with oxytocin. ... Oxymorphone (Opana, Numorphan) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic that is derived from thebaine, and is approximately 6–8 times more potent than morphine. ...

Synthetic opioids

Anilidopiperidines

• Fentanyl
• Alphamethylfentanyl
• Alfentanil
• Sufentanil
• Remifentanil
• Carfentanyl
• Ohmefentanyl

Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica (Belgium) in the late 1950s, with a potency many times that of morphine. ... α-methylfentanyl is an opioid analgesic that is an analogue of fentanyl. ... Alfentanil (Alfenta) is a parenteral short-acting opioid painkiller, used for anaesthesia in surgery. ... Sufentanil is a synthetic opioid analgesic drug approximately 5 to 10 times more potent than fentanyl. ... Remifentanil is a potent ultra short-acting synthetic opioid analgesic drug. ... Carfentanil, also Carfentanyl, is an analogue of the popular opiate Fentanyl, and is roughly 10,000 times stronger than Morphine. ... This article or section is not written in the formal tone expected of an encyclopedia article. ...

Phenylpiperidines

• Pethidine (meperidine)
• Ketobemidone
• MPPP
• Allylprodine
• Prodine
• PEPAP

Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland);[1] Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ... Ketobemidone structure Ketobemidone is a powerful opioid analgesic. ... MPPP (1-methyl 4-phenyl 4-propionoxypiperidine) is an opioid analgesic drug. ... Allylprodine is an opioid analgesic that is an analogue of prodine. ... Prodine (Prisilidine, Nisentil) is an opioid analgesic that is an analogue of pethidine (meperidine). ... PEPAP is an opioid analgesic that is an analogue of pethidine (meperidine). ...

Diphenylpropylamine derivatives

• Propoxyphene
• Dextropropoxyphene
• Dextromoramide
• Bezitramide
• Piritramide
• Methadone
• Dipipanone
• Levomethadyl Acetate (LAAM)
• Loperamide (used for diarrhoea, does not cross the blood-brain barrier)
• Diphenoxylate (used for diarrhoea, does not appreciably cross the blood-brain barrier)

Dextropropoxyphene is an analgesic in the opioid category that is used to treat severe pain and severe coughs. ... Dextropropoxyphene is an analgesic in the opioid category. ... Dextromoramide (Palfium®, Palphium®, Jetrium®, Dimorlin®) is the right-handed isomer of the moramide molecule. ... Bezitramide (4-[4-(2-oxo-3-propanoyl-benzoimidazol-1-yl)-1-piperidyl]-2,2-diphenyl-butanenitrile MW: 492. ... Piritramide (Dipidolor®) is a synthetic opioid analgesic with about 65-75 percent of the mg-for-mg strength of morphine. ... Methadone (Dolophine, Amidone, Methadose, Physeptone, Heptadon and many others) is a synthetic opioid, used medically as an analgesic, antitussive and a maintenance anti-addictive for use in patients on opioids. ... Dipipanone hydrochloride is an opioid painkiller. ... Levomethadyl acetate, also known as levo-α-acetylmethadol (LAAM) is a synthetic opioid similar in structure to methadone. ... Imodium redirects here. ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ... On opiod agonist used for the treatment of diarrhea. ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ...

Benzomorphan derivatives

• Dezocine
• Pentazocine
• Phenazocine

Dezocine (Dalgan, WY-16225) is an opioid analgesic related to pentazocine, with a similar profile of effects that include analgesic action and euphoria at low doses,[1] but produces dysphoria and hallucinations at high doses, most likely due to action at κ-opioid receptors. ... Pentazocine is a synthetically-prepared narcotic (opioid analgesic) drug used to treat mild to moderately severe pain. ... Phenazocine (Prinadol, Narphen) is an opioid analgesic, invented in the 1950s,[1][2] which is related to pentazocine and has a similar profile of effects that include analgesic action and euphoria, but may produce dysphoria and hallucinations at high doses, most likely due to action at κ-opioid and σ receptors. ...

Oripavine derivatives

• Buprenorphine
• Dihydroetorphine
• Etorphine

Oripavine is an opiate and the major metabolite of thebaine. ... Buprenorphine, is an opioid drug with partial agonist and antagonist actions. ... China is one of the only countries in the world to prescribe Dihydroetorphine, (a close relative of Etorphine) to humans. ... Etorphine (Immobilon or M99) is a semi-synthetic opioid possessing an analgesic potency approximately 10,000 times that of morphine and was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather in poppy straw and in related plants, Papaver orientale and Papaver...

Morphinan derivatives

• Butorphanol
• Nalbuphine
• Levorphanol
• Levomethorphan

Morphinan is the base chemical structures of a subgroup of opioids. ... Butorphanol (INN) is a morphinan-type synthetic opioid analgesic marketed in the U.S. under the trade name Stadol. ... Nalbuphine (nalbuphine hydrochloride) is a synthetic opioid used commercially as an analgesic under a variety of trade names, including Nubain. ... Levorphanol is an opioid medication used to treat severe pain. ... Levomethorphan is an optical isomer of dextromethorphan. ...

Others

• Lefetamine
• Meptazinol
• Tilidine
• Tramadol
• Tapentadol

Lefetamine is a psychoactive drug which has effects similar to both morphine and methylphenidate. ... Meptazinol is an opioid analgesic for use with moderate to severe pain, most commonly used to treat pain in obstetrics (childbirth). ... Tilidine (INN, USAN), or tilidate (BAN) (Valoron®, Valtran®, Tilidin) is a synthetic opioid analgesic, used for treatment of moderate to severe pain, both acute and chronic[1]. Considered a low- to medium-potency opioid, it has the oral potency of about 0. ... Tramadol (INN) (IPA: ) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. ... Tapentadol (INN) is a centrally-acting analgesic with a unique dual mode of action as an agonist at the μ-opioid receptor and as a norepinephrine reuptake inhibitor. ...

Opioid antagonists

• Nalmefene
• Naloxone
• Naltrexone

Nalmefene (Revex) is an opioid receptor antagonist used primarily in the management of alcohol dependence, and also has been investigated for the treatment of other addictions such as pathological gambling and addiction to shopping. ... Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. ... Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. ...

See also

• Psychoactive drug

An assortment of psychoactive drugs A psychoactive drug or psychotropic substance is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. ...

References

1. ^ Ohmefentanyl Analogue
2. ^ http://www.senliscouncil.net/modules/publications/008_publication
3. ^ The World Health Organisation "Assuring Availability of Opioid Analgesics" [www.euro.who.int/document/e76503.pdf]
4. ^ Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
5. ^ Wilson GR, Reisfield GM. "Morphine hyperalgesia: a case report." Am J Hosp Palliat Care. 2003 Nov-Dec;20(6):459-61. PMID 14649563
6. ^ Vella-Brincat J, Macleod AD. "Adverse effects of opioids on the central nervous systems of palliative care patients." J Pain Palliat Care Pharmacother. 2007;21(1):15-25. PMID 17430825
7. ^ Mercadante S, Arcuri E. "Hyperalgesia and opioid switching." Am J Hosp Palliat Care. 2005 Jul-Aug;22(4):291-4. Review. PMID 16082916
8. ^ Fine PG. "Opioid insights:opioid-induced hyperalgesia and opioid rotation." J Pain Palliat Care Pharmacother. 2004;18(3):75-9. Review. PMID 15364634
9. ^ Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
10. ^ McNicol E, Boyce D, Schumann R, Carr D. Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database of Systematic Reviews. 2008 Apr 16;(2):CD006332. PMID 18425947
11. ^ Portenoy RK, Thomas J, Moehl Boatwright ML, Tran D, Galasso FL, Stambler N, Von Gunten CF, Israel RJ. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. Journal of Pain and Symptom Management. 2008 May;35(5):458-68. PMID 18440447
12. ^ Yost CS. A new look at the respiratory stimulant doxapram. CNS Drug Reviews. 2006 Fall-Winter;12(3-4):236-49. PMID 17227289
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A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• American Pain Foundation
• Pain Relief Network (PRN)
• American Pain Society
• American Academy of Pain Management
• American Academy of Addiction Psychiatry, professional association of psychiatrists expert in addiction treatment
• CLiP- Current Learning in Palliative Care Fifty-six workshops on palliative care which can be used online or downloaded. Free access, no restrictions.
• International Association for Hospice and Palliative Care
• Palliativedrugs.com. Online palliative care formulary. Also has bulletin board with over 22,000 international professionals registered. Free access after registration.
• Palliative Care Matters Palliative Care information.
• Palliative Care Handbook Online palliative care textbook
• The use of opioids for chronic pain @ The APS
• Merck Entry on Opioids
• Pain

Bibliography

• Palliativedrugs.com Palliative Care Formulary and bulletin board with over 22,000 worldwide registered. Free to register.
• Wall and Melzack’s textbook of pain, 5th ed. Stephen B. McMahon and Martin Koltzenburg, eds. Edinburgh : Elsevier Churchill Livingstone, 2006.
• Gutstein, Howard B. and Huda Akil, “Opioid Analgesics”, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th Edition, 2006, edited by Brunton, Laurence L., John S. Lazo, Keith L. Parker, Iain L. O. Buxton, and Donald Blumenthal.
• Rossi S (Ed.) (2005). Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3.
• A Guide to Symptom Relief in Palliative Care, 5th ed. Regnard C, Hockley J. Abingdon: Radcliffe Medical Press, 2004
• PCF2- Palliative Care Formulary, 2nd ed. Twycross RG, Wilcock A, Charlesworth S. Abingdon: Radcliffe Medical Press, 2003.
• Oxford Textbook of Palliative Medicine 3rd ed. Doyle D, Hanks G, Cherny NI, Calman K eds. Oxford : Oxford University Press, 2003.
• Hanks GW. Conno F. Cherny N. Hanna M. Kalso E. McQuay HJ. Mercadante S. Meynadier J. Poulain P. Ripamonti C. Radbruch L. Casas JR. Sawe J. Twycross RG. Ventafridda V. Expert Working Group of the Research Network of the European Association for Palliative Care. Morphine and alternative opioids in cancer pain: the EAPC recommendations. British Journal of Cancer. 2001; 84(5): 587-93.
• Symptom Management in Advanced Cancer, 3rd edition. 2001. Twycross RG, Wilcock A. Abingdon: Radcliffe Medical Press.
• Hanks GW. Forbes K. Opioid responsiveness. Acta Anaesthesiologica Scandinavica. 1997; 41: 154-8.
• Cancer Pain Relief and Palliative Care. Geneva : WHO, 1990.
• Oral Morphine, Information for Patients, Families and Friends. Twycross R., Lack S.A. Beaconsfield Publishers. 1988.