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An opioid is a chemical substance that has a morphine-like action in the body. Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in 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. Opioid receptors are a group of G-protein coupled receptors with Opioids as Ligands The Endogenous Opioids are Dynorphins In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. The receptors in these two organ systems mediate both the beneficial effects, and the undesirable side effects. Side Effect were an influential Disco band that recorded between 1972 and 1995 There are a number of broad classes of opioids:

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. 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. Nefopam (marketed under the Brandname Acupan) is an Analgesic Drug, developed in the early 1970s Orphenadrine (sold under the Brand names Norflex Mephenamin Disipal Banflex Flexon Biorphen Brocasipal and others is an Anticholinergic Drug of Phenyltoloxamine is an Antihistamine with Sedative and Analgesic effects A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. 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, paracetamol, ibuprofen and the like.

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.


Contents

Pharmacology

Main article: opioid receptor

Opioids bind to specific opioid receptors in the central nervous system and in other tissues. Opioid receptors are a group of G-protein coupled receptors with Opioids as Ligands The Endogenous Opioids are Dynorphins Opioid receptors are a group of G-protein coupled receptors with Opioids as Ligands The Endogenous Opioids are Dynorphins In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. 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. The μ opioid receptors (MOR are a class of Opioid The κ-Opioid receptor is a type of Opioid receptor which binds the peptide opioid Dynorphin as the primary Endogenous ligand. The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an Opioid receptor that has 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. Naloxone is a drug used to counter the effects of Opioid overdose, for example Heroin or Morphine overdose Dextrorotation and levorotation (also spelled laevorotation) refer respectively to the properties of rotating plane Polarized light clockwise (for dextrorotation This article is about the chemical concept For "isomerism" of atomic nuclei see Nuclear isomer. Dextrorotation and levorotation (also spelled laevorotation) refer respectively to the properties of rotating plane Polarized light clockwise (for dextrorotation In addition, there are three subtypes of μ receptor: μ1 and μ2, and the newly discovered μ3. The μ opioid receptors (MOR are a class of Opioid 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. G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. Neurotransmission (latin transmissio = passage crossing from transmitto = send let through also called synaptic transmission, is an electrical movement 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. Pharmacodynamics is the study of the Biochemical and Physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms An agonist is a term used to describe a type of ligand or drug that binds and alters the activity of a receptor. A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks 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. Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in Each group of opioid receptors illicits 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). Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in 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].

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. Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled 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.

In recent years there has been an increased use of opioids in the management of non-malignant chronic pain. Chronic pain is defined as Pain that persists longer than the temporal course of natural healing associated with a particular type of injury or disease process 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.

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:

United States

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

In the U. Anesthesia, or anaesthesia (see spelling differences; from Greek grc αν- an-, "without" and grc αἲσθησις Loperamide, a synthetic Piperidine derivative is a drug effective against Diarrhea resulting from Gastroenteritis or Inflammatory Diphenoxylate ( Lomotil® Co-phenotrope and others is an Opioid agonist used for the treatment of Diarrhoea that acts by slowing intestinal contractions Laudanum (ˈlȯd-nəm or ˈlȯ-də-nəm also known as Opium Tincture or Tincture of Opium, is an Alcoholic herbal preparation Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from Oxymorphone ( Opana, Numorphan, Numorphone) or 14-Hydroxydihydro Morphinone is a powerful semi-synthetic Opioid Analgesic Buprenorphine (or colloquially "Bupe" is a semi-synthetic Opiate with partial agonist and antagonist actions 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).

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:

Not just opioids. . .

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) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan

History

Non-clinical use was criminalized in the U. S by the Harrison Narcotics Tax Act of 1914, and by other laws worldwide. The Harrison Narcotics Tax Act (Ch 1) was a United States federal law that regulated and taxed the production importation and distribution of Opiates. 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 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

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 International Narcotics Control Board (INCB is the independent and quasi-judicial control organ for the implementation of the United Nations drug conventions The Single Convention on Narcotic Drugs is an international Treaty to prohibit production and supply of specific (nominally Narcotic) Drugs and of 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]

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 The Senlis Council is an international Think tank known for its work in Afghanistan and other conflict zones such as Iraq and 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 Afghanistan /æfˈgænɪstæn/ officially the Islamic Republic of Afghanistan ( Pashto: د افغانستان اسلامي جمهوریت, The International Narcotics Control Board (INCB is the independent and quasi-judicial control organ for the implementation of the United Nations drug conventions

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. Miosis is Constriction of the Pupil of the Eye. This is a normal response to an increase in light but can also be associated with certain Pathological Fortunately, most of these are not a problem (see Treating Opioid Adverse Effects below).

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). Delirium is an acute and relatively sudden (developing over hours to days decline in attention-focus perception and Cognition. Hypothermia is a condition in which an organism's temperature drops below that required for normal Metabolism and bodily functions 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 Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which

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. Opioid-induced hyperalgesia or opioid-induced abnormal pain sensitivity is a phenomenon associated with the long term use of Opioids such as Morphine, This phenomenon, although uncommon, is seen in some palliative care patients, most often when dose is escalated rapidly. Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms [5] [6] If encountered, rotation between several different opioid analgesics may mitigate the development of hyperalgesia. [7] [8]

Both therapeutic and chronic use of opioids can compromise the function of the immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Opioids decrease the proliferation of macrophage progenitor cells and lymphocytes, and affect cell differentiation (Roy & Loh, 1996). Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Opioids may also inhibit leukocyte migration. However the relevance of this in the context of pain relief is not known.

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. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort g. low dose haloperidol 1. Haloperidol is a Typical antipsychotic. It is in the Butyrophenone class of Antipsychotic medications and has pharmacological effects similar 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. Ondansetron ( INN) (ɒnˈdænsɛtrɒn or Zofran is a Serotonin 5-HT3 receptor antagonist used mainly as an Antiemetic to Tropisetron ( INN) is a Serotonin 5-HT3 receptor antagonist used mainly as an Antiemetic to treat Nausea and Vomiting

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. Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the g. domperidone or metoclopramide 10mg every eight hours), but usually needs to be started by a non-oral route (e. Domperidone (trade name Motilium or Motillium) is an Antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally Metoclopramide ( INN) (ˌmɛtəˈkloʊprəmaɪd or /ˌmɛtəˈklɒprəmaɪd is a potent Dopamine receptor antagonist used for its Antiemetic and Prokinetic g. subcutaneous for metoclopramide, rectally for domperidone).

Drowsiness: tolerance usually develops over 5–7 days, but if troublesome, switching to an alternative opioid often helps. Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c 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. Fentanyl is one of the most powerful Opioid Analgesics with a potency approximately 81 times that of Morphine. Oxycodone is an Opioid Analgesic Medication synthesized from Thebaine. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan

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. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. 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. Fexofenadine hydrochloride (brand names include Allegra and Telfast) is an Antihistamine drug used in the treatment of Hayfever Orphenadrine (sold under the Brand names Norflex Mephenamin Disipal Banflex Flexon Biorphen Brocasipal and others is an Anticholinergic Drug of 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. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Promethazine is a first-generation H1 receptor antagonist Antihistamine and Antiemetic medication Dipipanone hydrochloride is an Opioid painkiller In combination with Cyclizine hydrochloride it is marketed as Diconal, indicated for relief of moderate Cyclizine is an Antihistamine drug used to treat Nausea, Vomiting and Dizziness associated with Motion sickness, vertigo

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. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that 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. Alvimopan ( Entereg) is a Drug which behaves as a peripherally acting μ-opioid antagonist. Methylnaltrexone ( MNTX, tradename Relistor) is one of the newer agents of peripherally-acting μ-opioid antagonists that act to reverse [10][11]

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 Medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate ( hypo means "below" to perform needed 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. Doxapram hydrochloride (marketed as Dopram) is a Respiratory stimulant. [12][13] Newer drugs such as BIMU-8 and CX-546 may however be much more effective. BIMU-8 is a drug which acts as a 5-HT4 receptor selective Agonist. CX-546 is an Ampakine drug developed by Cortex Pharmaceuticals [14][15][16]

Reversing the effect of opioids: Opioid effects can be rapidly reversed with an opioid antagonist (literally an inverse agonist) such as naloxone or naltrexone. An opioid antagonist is an Receptor antagonist that acts on Opioid receptors Naloxone and Naltrexone are commonly used opioid antagonist In Pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an Agonist for that receptor and reverses constitutive Naloxone is a drug used to counter the effects of Opioid overdose, for example Heroin or Morphine overdose Naltrexone is an Opioid receptor antagonist used primarily in the management of Alcohol dependence and Opioid dependence. These competitive antagonists bind to the opioid receptors with higher affinity than agonists but do not activate the receptors. A competitive antagonist is a Receptor antagonist that binds to a receptor but does not activate the receptor 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. The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Nalmefene (Revex is an Opioid receptor antagonist used primarily in the management of Alcohol dependence, and also has been investigated 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.

How safe are opioids? A world view

There are a number of paradoxical beliefs about opioids:


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]

Using opioids safely

Double effect

The principle of double effect is not used in palliative care. The principle of double effect ( PDE) also known as the rule of double effect ( RDE) the doctrine of double effect ( Doctors are not faced with the dilemma of giving a potentially lethal drug dose to a distressed patient. [32]

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. 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. Drug tolerance occurs when a subject's reaction to a Psychoactive drug (such as a painkiller or intoxicant decreases so that larger doses are required to achieve the same effect 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.

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. 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 Intrathecal is an adjetive that refers to something that happens inside of the spinal canal Magnesium (mægˈniːziəm is a Chemical element with the symbol Mg, Atomic number 12 Atomic weight 24 Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 NMDA receptor antagonists are a class of Anesthetics that work to antagonize, or inhibit the action of the N-methyl d-aspartate receptor ( NMDAR Ketamine is a drug for use in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962 [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. A Cholecystokinin antagonist is a specific type of Receptor antagonist which blocks the receptor sites for the Peptide Hormone Cholecystokinin Proglumide ( Milid) is a drug which inhibits gastrointestinal motility and reduces gastric secretions A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the Enzyme Phosphodiesterase (PDE therefore preventing the inactivation Ibudilast (current development codes AV-411 or MN-166) is an Antiinflammatory drug used mainly in Japan which acts as a Phosphodiesterase inhibitor [42]

Magnesium and zinc deficiency speed up the development of tolerance to opioids 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.

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. Dysphoria (from Greek δύσφορος (dysphoros from δυσ- difficult and φέρω to bear is generally characterized as an unpleasant or uncomfortable mood such as sadness Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm 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. Methadone ( Dolophine Amidone Methadose Physeptone Heptadon and many others is a synthetic Opioid, used medically as an Analgesic, Antitussive 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. Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic In Chemistry, an alcohol is any Organic compound in which a Hydroxyl group ( - O[[hydrogen H]]) is bound to a Carbon

Addiction

Addiction is the process whereby physical and/or psychological addiction develops to a drug - including opioids. Drug addiction is widely considered a pathological state. The disorder of addiction involves the progression of acute Drug use to the development of drug-seeking 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. Ibogaine is a naturally-occurring Psychoactive compound found in a number of plants principally in a member of the dogbane family known as iboga ( (--18-Methoxycoronaridine (18-MC is a derivative of Ibogaine invented in 1996 by the research team around the pharmacologist Stanley D [48]

Abuse

Drug abuse is the misuse of drugs producing negative consequences. Drug abuse has a wide range of definitions related to taking a Psychoactive drug or Performance enhancing drug for a non-therapeutic or non-medical effect

Examples of opioids

Endogenous opioids

Dunniod-peptides that are produced in the body include:

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. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Endorphins are Endogenous Opioid Polypeptide compounds They are produced by the Pituitary gland and the Hypothalamus in Vertebrates An enkephalin is a Pentapeptide involved in regulating Pain and Nociception in the body Dynorphins are a class of Opioid peptides that arise from the precursor Protein prodynorphin Endomorphins are two endogenous Opioid Peptides. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2 and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2 are Tetrapeptides Beta- Endorphin is an Endogenous Opioid Peptide Neurotransmitter found in the Neurons of both the central and Pro-opiomelanocortin ( POMC) is a precursor Polypeptide with 241 Amino acid residues The arcuate nucleus (or infundibular nucleus is an aggregation of Neurons in the mediobasal Hypothalamus, adjacent to the Third ventricle and the Median The brain stem (or brainstem) is the lower part of the Brain, adjoining and structurally continuous with the Spinal cord. β-endorphin has many effects, including on sexual behavior and appetite. Human sexual behavior or different human sexual practices encompass a wide range of activities such as strategies to find or attract partners ( Mating and display β-endorphin is also secreted into the circulation from pituitary corticotropes and melanotropes. Corticotropes (or corticotrophs are cells in the Anterior pituitary which produce Adrenocorticotrophic hormone and Melanocyte stimulating hormone α-neoendorphin is also expressed in POMC cells in the arcuate nucleus.

[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. An enkephalin is a Pentapeptide involved in regulating Pain and Nociception in the body [leu]-enkephalin, also a product of the proenkephalin gene, acts through δ-opioid receptors. An enkephalin is a Pentapeptide involved in regulating Pain and Nociception in the body

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. Dynorphins are a class of Opioid peptides that arise from the precursor Protein prodynorphin The spinal cord is a long thin tubular bundle of Nerves that is an extension of the Central nervous system from the brain and is enclosed in and protected The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis The arcuate nucleus (or infundibular nucleus is an aggregation of Neurons in the mediobasal Hypothalamus, adjacent to the Third ventricle and the Median Oxytocin ( IPA: /ˌɔksɪˈtoʊsɪn/ (Greek "quick birth" is a Mammalian Hormone that also acts as a Neurotransmitter in the Arginine vasopressin ( AVP) also known as vasopressin, argipressin or antidiuretic hormone ( ADH) is a Hormone found in 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. Endomorphins are two endogenous Opioid Peptides. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2 and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2 are Tetrapeptides

Opium alkaloids

Phenanthrenes naturally occurring in opium:

Preparations of mixed opium alkaloids, including papaveretum, are still occasionally used. Phenanthrene is a Polycyclic aromatic hydrocarbon composed of three fused Benzene rings Opium is a Narcotic formed from the Latex (ie sap released by lacerating (or "scoring" the immature seed pods of opium poppies ( Codeine ( INN) or methylmorphine is an Opiate used for its Analgesic, antitussive and antidiarrheal properties Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in Parameters work only in their own section When a parameter is not needed please leave it empty when a parameter is wrong just clear Oripavine is an Opiate and the major metabolite of Thebaine. It is the prototypical molecule of a series of semi-synthetic Papaveretum ( BAN) is a preparation containing a mixture of Hydrochloride salts of Opium Alkaloids Since 1993, papaveretum has been

Semisynthetic derivatives

Synthetic opioids

Anilidopiperidines

Phenylpiperidines

Diphenylpropylamine derivatives

Benzomorphan derivatives

Oripavine derivatives

Morphinan derivatives

Others

Opioid antagonists

See also

References

  1. ^ Ohmefentanyl Analogue
  2. ^ http://www.senliscouncil.net/modules/publications/008_publication
  3. ^ The World Health Organisation "Assuring Availability of Opioid Analgesics" [www. Heroin ( INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from Morphine, a derivative Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Hydrocodone or dihydrocodeinone is a semi-synthetic Opioid derived from two of the naturally occurring Opiates Codeine and Thebaine Hydromorphone, a more common synonym for dihydromorphinone hydrochloride (trade names Palladone IR, Palladone SR, Dilaudid and numerous others Nicomorphine ( Vilan, Subellan, Gevilan, MorZet) is the 36-dinicotinate Ester of Morphine. Oxycodone is an Opioid Analgesic Medication synthesized from Thebaine. Oxymorphone ( Opana, Numorphan, Numorphone) or 14-Hydroxydihydro Morphinone is a powerful semi-synthetic Opioid Analgesic Fentanyl is one of the most powerful Opioid Analgesics with a potency approximately 81 times that of Morphine. α-methylfentanyl is an Opioid Analgesic that is an analogue of Fentanyl. Alfentanil (trade name Alfenta) is a potent but short-acting synthetic Opioid Analgesic drug, used for Anaesthesia in Surgery Sufentanil is a synthetic Opioid Analgesic drug approximately 5 to 10 times more potent than Fentanyl. Remifentanil (marketed by GlaxoSmithKline and Abbott as Ultiva) is a potent ultra short-acting synthetic Opioid Analgesic drug. Carfentanil or Carfentanyl (R33799 is an analogue of the popular synthetic Opioid Analgesic Fentanyl, and is one of the most potent opioids Ohmefentanyl (β-hydroxy-3-methylfentanyl is an extremely potent Analgesic drug which selectively binds to the µ-opioid receptor. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Ketobemidone (Cliradon Ketogan Ketodur Cymidon Ketorax &c is a powerful Opioid Analgesic. MPPP ( 1-methyl-4-phenyl-4-propionoxypiperidine, Desmethylprodine) 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 Dextropropoxyphene is an Analgesic in the Opioid category It is used to treat mild to moderate pain and as an Anti-tussive. Dextropropoxyphene is an Analgesic in the Opioid category It is used to treat mild to moderate pain and as an Anti-tussive. Dextromoramide (Palfium Palphium Jetrium Dimorlin is a powerful Opioid Analgesic approximately three times more potent than morphine but shorter acting Bezitramide is a narcotic Analgesic. Bezitramide itself is a Prodrug which is readily hydrolyzed in the Gastrointestinal tract to its main Piritramide ( Dipidolor, Piridolan, Pirium and others is a synthetic Opioid Analgesic with a potency 0 Methadone ( Dolophine Amidone Methadose Physeptone Heptadon and many others is a synthetic Opioid, used medically as an Analgesic, Antitussive Dipipanone hydrochloride is an Opioid painkiller In combination with Cyclizine hydrochloride it is marketed as Diconal, indicated for relief of moderate Levomethadyl acetate, also known as levo-α-acetylmethadol (LAAM is a synthetic Opioid similar in structure to Methadone. Loperamide, a synthetic Piperidine derivative is a drug effective against Diarrhea resulting from Gastroenteritis or Inflammatory The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic Diphenoxylate ( Lomotil® Co-phenotrope and others is an Opioid agonist used for the treatment of Diarrhoea that acts by slowing intestinal contractions The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic Dezocine (Dalgan WY-16225 is an Opioid Analgesic related to Pentazocine, with a similar profile of effects that include analgesic action and euphoria Pentazocine is a synthetically-prepared prototypical mixed agonist-antagonist Narcotic ( Opioid Analgesic) drug used to treat mild to moderately severe pain Phenazocine ( Brandnames Prinadol, Narphen) is an Opioid Analgesic Drug, which is related to Pentazocine and has Oripavine is an Opiate and the major metabolite of Thebaine. It is the prototypical molecule of a series of semi-synthetic Buprenorphine (or colloquially "Bupe" is a semi-synthetic Opiate with partial agonist and antagonist actions Dihydroetorphine is a potent Analgesic drug (painkiller which is used mainly in China Etorphine ( Immobilon or M99) is a semi-synthetic Opioid possessing an Analgesic potency approximately 10000 times that of Morphine Morphinan is the base chemical structure of a subgroup of Opioids It is also an alternative name for the drug Dromoran, which is a racaemic parent drug of Levo-Dromoran® Butorphanol ( INN) is a Morphinan -type synthetic Opioid Analgesic. Nalbuphine (nalbuphine hydrochloride is a synthetic Opioid used commercially as an Analgesic under a variety of trade names including Nubain. Levorphanol (Levo-Dromoran is an Opioid medication used to treat severe pain Levomethorphan is the l- Stereoisomer of Methorphan. The effects of the two isomers are quite different Lefetamine (Santenol is a psychoactive drug which is both a Stimulant and an Analgesic with effects comparable to both Morphine and Methylphenidate Meptazinol ( Meptid) is an Opioid Analgesic for use with moderate to severe Pain, most commonly used to treat pain in Obstetrics Tilidine ( INN, USAN) or tilidate ( BAN) (Valoron Valtran Tilidin is a synthetic Opioid analgesic used for treatment of moderate Tramadol ( INN) (ˈtræmədɒl 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 Nalmefene (Revex is an Opioid receptor antagonist used primarily in the management of Alcohol dependence, and also has been investigated Naloxone is a drug used to counter the effects of Opioid overdose, for example Heroin or Morphine overdose Naltrexone is an Opioid receptor antagonist used primarily in the management of Alcohol dependence and Opioid dependence. A psychoactive drug or psychotropic substance is a Chemical substance that acts primarily upon the Central nervous system where it alters Brain euro. who. int/document/e76503. pdf]
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External links

Bibliography


Dictionary

opioid

-noun

  1. A substance that is like opium.
  2. (physiology) Any of the natural substances, such as an endorphin, released in the body in response to pain.
  3. (pharmacology) Any of a group of synthetic compounds that exhibit similarities to the opium alkaloids that occur in nature.

-adjective

  1. Pertaining to opioids.
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