Opioid

src: www.healthline.com

Opioids are substances that act on opioid receptors to produce effects such as morphine. Medically they are mainly used for pain relief, including anesthesia. Other medical uses include diarrheal suppression, replacement therapy for opioid use disorders, reversing opioid overdose, suppressing cough, and suppressing opioid-induced constipation. Very powerful opioids such as carfentanil are only approved for animal use. Opioids are also often used non-medically for their euphoric effects or to prevent withdrawal.

Opioid side effects may include itching, sedation, nausea, respiratory depression, constipation, and euphoria. Tolerance and dependence will develop with continuous use, requiring increased doses and leading to a withdrawal syndrome after abrupt cessation. Euphoria attracts recreational and frequent use, increasing recreational use of opioids usually results in addiction. The use of an overdose or concurrent with other depressant drugs usually causes death from respiratory depression.

Opioids act by binding to opioid receptors, which are found primarily in the central nervous system and peripheral and digestive tracts. These receptors mediate the psychoactive and opioid somatic effects. Opioid drugs include partial agonists, such as the anti-diarrhea drug loperamide and antagonists such as naloxegol for opioid-induced opioid, which does not pass through the blood-brain barrier, but can replace other opioids from binding to the receptor.

Because of the reputation of opioid drugs for addictions and fatal overdoses, most are controlled substances. In 2013, between 28 and 38 million people used opioids illegally (0.6% to 0.8% of the global population between the ages of 15 and 65). In 2011, an estimated 4 million people in the United States use opioids on a recreational basis or rely on them. In 2015, increased levels of recreational use and addiction are associated with over-opioid drug prescription and inexpensive forbidden heroin. Conversely, concerns about overly prescribing, excessive side effects and addiction from opioids are equally blamed for lack of pain treatment.

Video Opioid

Terminology

Opioids include opiates, an old term referring to opium-derived drugs, including morphine itself. Other opioids are synthetic and synthetic semi-synthetic drugs such as hydrocodone, oxycodone and fentanyl; antagonistic drugs such as naloxone; and endogenous peptides such as endorphins. The terms opiates and narcotics are sometimes encountered as synonyms for opioids. Opiates are correctly limited to natural alkaloids found in opium poppy resins although some include semi-synthetic derivatives. Narcotic , derived from words that mean 'numbness' or 'sleep', as an American legal term, refers to cocaine and opioids, and their source material; it is also loosely applied to any illegal psychoactive drugs. In some jurisdictions all legally controlled drugs are classified as narcotics . This term can have a condescending connotation and its use is generally not recommended where it occurs.

Maps Opioid

Medical use

Pain

Opioids are indicated to relieve mild to severe pain, but are usually used for moderate to severe pain. Weak opioid codeine, in low doses and combined with one or more other drugs, is generally available without a prescription.

Acute pain

Opioids are effective for the treatment of acute pain (such as pain after surgery). To immediately relieve moderate to severe acute opioids, it is often a treatment option because of its rapid onset, efficacy and reduced risk of dependence. They have also been found to be important in palliative care to help with severe, chronic, disabling pain that can occur in some terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis. In many cases opioids are a successful long-term care strategy for those suffering from chronic cancers.

Chronic non-cancer pain

The guidelines have suggested that opioid risks may outweigh the benefits when used for most non-cancer chronic conditions including headaches, back pain, and fibromyalgia. Thus they should be used with caution in chronic non-cancer pain. If used, benefits and dangers should be reviewed at least every three months.

In treating chronic pain, opioids are an option to try after other less risky pain relievers have been considered, including paracetamol/acetaminophen or NSAIDs such as ibuprofen or naproxen. Some types of chronic pain, including pain caused by fibromyalgia or migraine, are preferably treated with drugs other than opioids. The efficacy of opioid use to reduce chronic neuropathic pain is uncertain.

Opioids are contraindicated as first-line treatment for headaches because they interfere with alertness, carry the risk of dependence, and increase the risk that episodic headaches will become chronic. Opioids may also cause increased sensitivity to headache pain. When other treatments fail or are not available, opioids may be appropriate to treat headaches if the patient can be monitored to prevent the development of chronic headaches.

Opioids are used more frequently in the management of chronic pain that is not malignant. This practice has now led to new and growing problems with addiction and opioid abuse. Because of the negative effects of opioid use for long-term management of chronic pain is not indicated unless other less risky pain relievers have been found to be ineffective. Chronic pain that occurs only periodically, such as that of nerve pain, migraine, and fibromyalgia, is often better treated with drugs other than opioids. Paracetamol and nonsteroidal antiinflammatory drugs including ibuprofen and naproxen are considered a safer alternative. They are often used in combination with opioids, such as paracetamol combined with oxycodone (Percocet) and ibuprofen in combination with hydrocodone (Vicoprofen), which increases pain relief but are also intended to prevent recreational use.

More

Cough

Kodein was once seen as the "gold standard" in cough suppressants, but this position is now being questioned. Several recent placebo-controlled trials have found that it may not be better than placebo for several causes including acute cough in children. So, it is not recommended for children. In addition, there is no evidence that hydrocodone is useful in children. Similarly, the 2012 Dutch guideline on acute cough medicine does not recommend its use. (Opioid dextromethorphan analogues, long claimed to be effective cipro-suppressant as codeine, show little benefit in recent studies.)

Low dose morphine can help chronic cough but its use is limited by side effects.

Diarrhea and constipation

In the case of irritable bowel irritation syndrome, opioids may be used to suppress diarrhea. Loperamide is a peripheral selective opioid available without a prescription used to suppress diarrhea.

The ability to suppress diarrhea also produces constipation when opioids are used beyond a few weeks. Naloxegol, a peripheral selective opioid antagonist now available to treat opioid-induced constipation.

Shortness of breath

Opioids can help with shortness of breath, especially in advanced diseases such as cancer and COPD.

src: www.searcylaw.com

Adverse effects

In older adults, the use of opioids is associated with increased side effects such as "sedation, nausea, vomiting, constipation, urinary retention, and falls". As a result, older adults who take opioids are at greater risk of injury. Opioids do not cause specific organ toxicities, unlike many other drugs, such as aspirin and paracetamol. They are not associated with upper gastrointestinal bleeding and renal toxicity.

Research shows that when methadone is used in the long run, it can build up unexpectedly in the body and cause breathing to slow down. Used medically, approaching toxicity is not recognized because the effects of pain medication end well before the half-time of drug elimination. According to the USCDC, methadone is involved in 31% of opioid-related deaths in the US between 1999-2010 and 40% as a single drug involved, much higher than other opioids. Long-term opioid studies have found that it can stop them and minor side effects are common. Addition occurs at about 0.3%. In the United States by 2016 an opioid overdose resulted in 1.7 deaths in 10,000 people.

Improvement disorder

Tolerance

Tolerance is a process characterized by a neuro adaptation that results in reduced drug effects. Although increased regulation of receptors often plays an important role, other mechanisms are also known. Tolerance is more pronounced for some effects than others; Tolerance occurs slowly to effects on mood, itching, urinary retention, and respiratory depression, but occurs more rapidly in analgesia and other physical side effects. However, tolerance does not develop into constipation or miosis (narrowing of the pupils to be less than or equal to two millimeters). This idea has been challenged, however, with some authors arguing that the tolerance does not develop into miosis.

Tolerance of opioid is weakened by a number of substances, including:

• calcium channel blockers
• magnesium and zinc intrathecal
• NMDA antagonists, such as dextromethorphan, ketamine, and fasting.
• antagonist cholecystokinin, such as proglumide
• New agents such as ibudilast phosphodiesterase inhibitors have also been researched for this application.

Tolerance is a physiological process in which the body adapts to a drug that often exists, usually requiring higher doses of the same drug over time to achieve the same effect. This is a common occurrence in individuals who use high-dose opioids for a long time, but does not predict any association for abuse or addiction.

Physical dependency

Physical dependence is the body's physiological adaptation to the existence of a substance, in this case an opioid drug. This is defined by the development of withdrawal symptoms when the substance is discontinued, when the dose is reduced abruptly or, specifically in the case of opioids, when antagonists (eg eg , naloxone) or antagonists (eg < >, pentazocine) is given. Physical dependence is a normal and expected aspect of certain drugs and does not necessarily mean that patients are addicted.

Symptoms of withdrawal for opiates may include severe dysphoria, desire for other opiate doses, irritation, sweating, nausea, rhinorrhea, tremors, vomiting and myalgia. Gently reducing opioid intake for several days and weeks can reduce or eliminate withdrawal symptoms. The speed and severity of withdrawal depend on the opioid beak; withdrawal of heroin and morphine occurs faster than methadone withdrawal. The acute withdrawal phase is often followed by a prolonged phase of depression and insomnia that can last for months. Symptoms of withdrawal of opioids can be treated with other drugs, such as clonidine. Physical dependence does not predict drug abuse or true addiction, and is closely related to the same mechanism with tolerance. Although there are anecdotal claims about benefits with ibogaine, the data to support its use in substance dependence is poor.

Dependency

Drug addiction is a complex set of behaviors that are typically associated with the misuse of certain drugs, evolving over time and with higher drug doses. Addictions include psychological distress, as long as the patient continues in actions that lead to harmful or unhealthy outcomes. Opioid addiction includes insufflation or injections, rather than using oral opioids as prescribed for medical reasons.

In European countries such as Austria, Bulgaria, and Slovakia, oral slow release morphine formulations are used in opioid substitution therapy (OST) for patients who can not tolerate the side effects of buprenorphine or methadone well. In other European countries including the UK, this is also legally used for OST though on varying acceptance scales.

Time-controlled drug release formulations aimed at curbing abuse and addiction levels while trying to keep giving legitimate pain relief and ease of use for pain patients. However, the question remains about the efficacy and safety of these types of preparations. Further resistant destructive drugs are currently being considered with trials for market approval by the FDA.

The amount of evidence available only makes a weak conclusion, but it shows that a doctor correctly manages the use of opioids in patients without a history of substance dependence or substance abuse can provide long-term pain relief with little risk of developing addiction, abuse, or other serious side effects.

Problems with opioids include the following:

1. Some people find that opioids do not eliminate all their pain.
2. Some people find that opioid side-effects cause a greater problem than therapeutic benefits
3. Some people build tolerance to opioids over time. This requires them to increase the doses of their medicines to preserve the benefits, and in turn also increase unwanted side effects.
4. Long-term use of opioids may induce opioid-induced hyperalgesia, which is a condition in which patients experience increased sensitivity to pain.

All opioids can cause side effects. Common side effects in patients taking opioids for pain relief include nausea and vomiting, drowsiness, itching, dry mouth, dizziness, and constipation.

Nausea and vomiting

Tolerance for nausea occurs within 7-10 days, where antiemetics (eg, low doses of haloperidol at night) are very effective. Because of severe side effects such as tardive dyskinesia, haloperidol is now rarely used. Drug related, prochlorperazine is more commonly used, although it has similar risks. Stronger antiemetics such as ondansetron or Pantaietron are sometimes used when nausea is severe or continuous and disturbing, although the cost is greater. The cheaper alternative is dopamine antagonists such as domperidone and metoclopramide. Domperidone does not cross the blood brain barrier and produces an adverse central antidopaminergic effect, but it blocks the action of opioid emic in the chemoreceptor trigger zone. (This drug is not available in the US) Some antihistamines with anticholinergic properties ( eg. orphenadrine or diphenhydramine) may also be effective. First generation hydroxyzine antihistamines are very commonly used, with the added benefit of not causing motion impairment, and also having a sparing-analgesic properties. ? ⁹ -tetrahydrocannabinol relieves nausea and vomiting; it also produces analgesia that allows low-dose opioids by reducing nausea and vomiting.

• 5-HT ₃ antagonist ( for example. ondansetron)
• Dopamine antagonists ( eg domperidone)
• Antihypercinic Antihistamines ( for example. diphenhydramine)
• ? ⁹ -tetrahydrocannabinol ( for example. dronabinol)

Vomiting is due to stasis of the stomach (large volume vomiting, mild nausea lost due to vomiting, esophageal reflux, epigastric fullness, early satiety), in addition to direct action on the macroepeptic zone of the postrema area, the brain's vomiting center. Vomiting may be prevented by prokinetic agents (eg, domperidone or metoclopramide). If vomiting has already begun, these drugs need to be given by a non-oral route ( eg. subcutaneously for metoclopramide, rectal for domperidone).

• Prokinetic agent ( for example domperidone)
• Anti-cholinergic agents ( for example. orphenadrine)

Drowsiness

Tolerance to drowsiness usually develops over 5-7 days, but if problematic, switch to alternative opioids often helps. Certain opioids such as fentanyl, morphine, and diamorphine (heroin) tend to be very sedating, while others such as oxycodone, tilidine and meperidine (pethidine) tend to produce relatively less sedation, but individual patient responses may vary significantly and some possible trial and error rates needed to find the most suitable drug for a particular patient. Otherwise, treatment with CNS stimulants is generally effective.

• Stimulants ( eg. caffeine, modafinil, amphetamine, methylphenidate)

Itch

Itching tends not to be a severe problem when opioids are used to relieve pain, but antihistamines are useful to counteract itching when it occurs. Non-sedating antihistamines such as fexofenadine are often preferred because they avoid the increased drowsiness caused by opioids. However, some sedative antihistamines such as orphenadrine can produce a synergistic pain relief effect that allows the use of opioids in smaller doses. Consequently, several opioid/antihistamine combination products have been marketed, such as Meprozine (meperidin/promethazine) and Diconal (dipipanone/cyclizine), and this can also reduce the induced opioid sickness.

• Antihistamines ( eg fexofenadine)

Constipation

Opioid-induced constipation (OIC) develops in 90 to 95% of people taking long-term opioids. Since tolerance to this problem does not develop easily, most people with long-term opioids need to take laxatives or enemas. While all opioids cause constipation, there are some differences between drugs, with studies showing tramadol, tapentadol, methadone and fentanyl may cause relatively less constipation, whereas codeine, morphine, oxycodone or constipation hydromorphon may be relatively more severe. Opioid rotation is commonly used to try and minimize the effects of constipation on long-term users.

Treatment

OIC treatment is successful and depends on the severity. The first mode of treatment is non-pharmacological, and includes lifestyle modifications such as increased dietary fiber, fluid intake (about 1.5 °, Â ° L (51 × US, fl × oz) per day), and physical activity. If non-pharmacological measures are ineffective, laxatives, including stool softeners (eg, , docusate), mass-forming laxatives (eg, , fiber supplements), stimulant laxatives ( eg , bisacodyl, senna), and/or enema, may be used. A common laxative regimen for OIC is a combination of docusate and bisacodyl. Osmotic laxatives, including lactulose, polyethylene glycol, and milk magnesia (magnesium hydroxide), as well as mineral oil (laxative lubricants), are also commonly used for OIC.

If the laxatives are not effective enough (which often happens), opioid formulations or regimens that include peripheral selective opioid antagonists, such as methylnaltrexone bromide, naloxegol, alvimopan, or naloxone (as in oxycodone/naloxone) can be tried. A Cochrane 2008 review found that the evidence was tentative for alvimopan, naloxone, or methylnaltrexone bromide.

Respiratory Depression

Respiratory depression is the most serious adverse reaction associated with opioid use, but is usually seen with the use of a single, intravenous dose in opioid-naÃÆ'¯ve patients. In patients taking regular opioids for pain relief, tolerance for respiratory depression occurs rapidly, so this is not a clinical problem. Several drugs have been developed that may block some respiratory depression, although the only respiratory stimulant currently approved for this purpose is doxapram, which has only limited efficacy in this application. Newer medications such as BIMU-8 and CX-546 may be much more effective.

• Respiratory stimulants: carotid chemoreceptor agonists ( eg doxapram), 5-HT agonists ₄ ( eg BIMU8) ,? - opioid agonists (eg BW373U86) and AMPAkines (eg CX717) all can alleviate respiratory depression caused by opioids without affecting analgesia, but most of these drugs are only effective or have side effects that hinder the use in humans. 5-HT _1A agencies such as 8-OH-DPAT and repinotan also fight opioid-induced respiratory depression, while at the same time reducing analgesia, which limits its usefulness for this application.
• opioid antagonists ( eg. naloxone, nalmefene, diprenorphine)

Opioid-induced opioid hyperalgesia

Opioid-induced hyperalgesia - in which individuals who use opioids to relieve pain paradoxically experience more pain as a result of the treatment - has been observed in some people. This phenomenon, though not common, is seen in some people receiving palliative care, most often when doses increase rapidly. If present, rotation between different opioid pain medications can decrease the development of increased pain. Opioid-induced hyperalgesia is more common with chronic or high-dose short-term use but some studies suggest that it can also occur at very low doses.

Side effects such as hyperalgesia and allodynia, sometimes accompanied by worsening of neuropathic pain, may be a consequence of long-term treatment with opioid analgesics, especially when increased tolerance has resulted in loss of efficacy and increased dose-related effects over time. This appears to be largely the result of opioid drug action on targets other than three classic opioid receptors, including nociceptin receptors, sigma receptors and Toll-like 4 receptors, and can be neutralized in animal models by antagonists on this target such as J-113,397, BD -1047 or () - naloxone respectively. No drug is currently approved specifically to counter opioid-induced hyperalgesia in humans and in severe cases the only solution is to stop the use of opioid analgesics and replace it with non-opioid analgesic drugs. However, since the individual's sensitivity to the development of these side effects is highly dose-dependent and may vary depending on the opioid analgesics used, many patients can avoid these side effects only by reducing the dose of opioid drugs (usually accompanied by the addition of non-opioid analgesic supplements), rotating between drugs different opioids, or by switching to lighter opioids with mixed action modes that also fight neuropathic pain, especially tramadol or tapentadol.

• NMDA receptor antagonists such as ketamine
• SNRI is like a milnacipran
• Anticonvulsants such as gabapentin or pregabalin

Other adverse effects

Low sex hormone levels

Clinical studies are consistently related to the use of medical and recreational opioids with hypogonadism (low sex hormone levels) in different sexes. The effect is dose dependent. Most studies show that the majority (perhaps as much as 90%) of chronic opioid users suffer from hypogonadism. Opioids can also disrupt menstruation in women by limiting the production of luteinizing hormone (LH). Opioid-induced hypogonadism may lead to a strong association of opioid use with osteoporosis and bone fracture, due to estradiol deficiency. It can also increase pain and thus interfere with the clinical effect of opioid treatment. Opioid-induced hypogonadism is probably caused by opioid receptor agonists in the hypothalamus and pituitary gland. One study found that declining testosterone levels from heroin addicts returned to normal within a month without abstinence, suggesting that the effect is easily reversed and not permanent. In 2013, the effect of using low or acute doses of opioids in the endocrine system is unclear.

Work disturbance

The use of opioids may be a risk factor of failing to work again.

People who perform safety-sensitive tasks should not use opioids. Healthcare providers should not recommend that workers driving or using heavy equipment including cranes or forklifts treat chronic or acute pain with opioids. Workplaces that manage workers who perform safety-sensitive operations should assign workers to less sensitive tasks as long as the workers are treated by their physicians with opioids.

People who use opioids in the long run are likely to become unemployed. Taking further opioids can disrupt the patient's life and the detrimental effects of opioids alone can be a significant deterrent for patients who have an active life, get a job, and maintain a career.

In addition, the lack of work can be a predictor of the use of prescription opioid deviations.

Increased accident prone

The use of opioids may increase accident-prone. Opioids can increase the risk of accidental traffic and accidental fall.

Rare side effects

Rare side effects in patients taking opioids for pain relief include: respiratory-related respiratory depression (especially with stronger opioids), confusion, hallucinations, delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness, headache , urinary retention, ureter or biliary spasms, muscle stiffness, myoclonus (with high doses), and redness (due to histamine release, except fentanyl and remifentanil). Both therapeutic and chronic use of opioids may compromise the functioning of the immune system. Opioids decrease proliferation of macrophages and lymphocyte progenitor cells, and affect cell differentiation (Roy & Loh, 1996). Opioids may also inhibit leukocyte migration. But this relevance in the context of pain relief is unknown.

src: mediad.publicbroadcasting.net

Interactions

Physicians who treat patients who use opioids in combination with other drugs constantly document that further care is indicated and remain aware of the opportunities to adjust the treatment if the patient's condition changes for less risky therapy.

With other depressant drugs

The use of opioids along with other depressant drugs such as benzodiazepines or ethanol increases the rate of side effects and overdose. Like overdose of opioids alone, the combination of opioids and other depressants can accelerate the respiratory depression that often leads to death. This risk is reduced by close monitoring by physicians, who can perform continuous screening for changes in patient behavior and medication adherence.

opioid antagonist

Opioid effects (harmful or otherwise) may be reversed with opioid antagonists such as naloxone or naltrexone. This competitive antagonist binds opioid receptors with higher affinity than agonists but does not activate receptors. This replaces the agonist, diluting or reversing the agonist effect. However, the half-life of naloxone elimination may be shorter than the opioid itself, so repeated dosing or continuous infusions may be necessary, or long-acting antagonists such as nalmephenes may be used. In patients taking regular opioids it is important that opioids are only partially reversed to avoid severe and distressing reactions from waking in extreme pain. This is achieved by not giving the full dose but giving this in small doses until the respiratory rate increases. The infusion then begins to maintain a reversal at that level, while maintaining the pain relievers. Opioid antagonists remain the standard treatment for respiratory depression following an overdose of opioids, with naloxone becoming the most commonly used, although longer-acting nalmefene antagonists may be used to treat overdose of long-acting opioids such as methadone, and diprenorphine is used to reverse the powerful opioid effects used in veterinary medicine such as etorphine and carfentanil. However, since opioid antagonists also block the beneficial effects of opioid analgesics, they are generally useful only to treat overdoses, with the use of opioid antagonists along with opioid analgesics to reduce side effects, require careful dosing titration and often become less effective at doses low enough to let analgesia is maintained.

src: rxight.com

Pharmacology

Opioids bind to specific opioid receptors in the nervous system and other tissues. There are three main classes of opioid receptors,?,?,? (mu, kappa, and delta), although up to seventeen have been reported, and include?,?,?, and? (Epsilon, Iota, Lambda and Zeta) receptors. Conversely,? Receptors (Sigma) are no longer considered opioid receptors because their activation is not reversed by naloxone inverse-agonist opioids, they show no high affinity bonds for classical opioids, and they are stereoselective for dextro-rotator isomers while others are selective-stereo opioid receptors for isomers -isomer levo-rotator. In addition, there are three subtypes of "receptors:? ₁ and? ₂ , and newly discovered ones? ₃ Other clinically important receptors are receptor opioid receptor 1 (ORL1), which is involved in the pain response and has a major role in the development of tolerance to agonists -opioids used as analgesics.These are all G-protein receptors that work on GABAergic neurotransmission.

The pharmacodynamic response to opioids depends on the receptor binding it, its affinity to the receptor, and whether the opioid is an agonist or an antagonist. For example, the supraspinal analgesic properties of opioid morphine agonists are mediated by activation of receptor " ₁ , respiratory depression and physical dependence by receptors ₂ , and spinal sedation and analgesia by receptors. the opioid receptor group generates a series of different neurological responses, with receptor subtypes (such as ₁ and < ₂ for example) providing more specific (measurable) responses.Unique for each opioid is the different binding affinities to different opioid receptor classes (eg opioid receptor, Æ' and, and Æ') are activated at different magnitudes according to the specific prescription-binding affinity of the opioid.) For example, opiate opioid morphine represents an affinity bond which is high against the -opioid receptors, while ketazocine exhibits a high affinity for the "receptor." This is a combinatorial mechanism that allows for opioid classes and molecular design er to exist, each with its own unique effects profile. Their individual molecular structure is also responsible for different duration of action, where metabolic damage (such as N -dealkylation) is responsible for opioid metabolism.

Functional selectivity

New drug development strategies require receptor signal transduction to be considered. This strategy seeks to increase the activation of the desired signal path while reducing the impact on the undesirable path. This differential strategy has been given several names, including functional selectivity and biased agonism. The first opioid deliberately designed as a biased agonist and placed into clinical evaluation is the oliceridine drug. It displays analgesic activity and reduces side effects.

Opioid Comparison

Extensive research has been done to determine the equivalence ratio that compares the relative potential of opioids. Given an opioid dose, the equianalgesic table is used to find an equivalent dose of the other. Such tables are used in the practice of opioid rotation, and to describe opioids as compared to morphine, reference opioids. The equianalgesic table is usually a part-time drug list, and sometimes the equianalgesic dose of the same drug by administration, such as morphine: oral and intravenous.

Bind profile

src: thedailycougar.com

Usage

Opioid recipes in the US increased from 76 million in 1991 to 207 million in 2013.

In the 1990s, opioid prescriptions increased significantly. After being used almost exclusively for the treatment of acute pain or cancer pain, opioids are now prescribed freely for people with chronic pain. This has been accompanied by an increased level of unintentional addiction and an accidental overdose that causes death. According to the International Narcotics Control Agency, the United States and Canada lead the consumption of prescription opioids per capita. The number of opioid prescriptions in the United States and Canada is double the consumption in the EU, Australia, and New Zealand. Certain populations have been affected by the opioid addiction crisis more than others, including the First World community and low-income populations. Public health experts say that this may be due to the unavailability or high cost of alternative methods for treating chronic pain.

src: thedoctorweighsin.com

History

Opioids are one of the oldest drugs in the world. The use of opium poppy for medical, recreational, and religious purposes can be traced back to the 4th century BC, when used by Sumerian and Hippocrates writing about it for its analgesic properties; "Divinum opus est sedare dolores".

In the 19th century morphine was isolated and marketed, and hypodermic needles were discovered, introducing the rapid and measurable delivery of primary compounds. Synthetic opioids are found, and biological mechanisms were discovered in the 20th century.

Non-clinical use was criminalized in the United States by the Harrison Narcotics Tax Act of 1914, and by other laws around the world. Since then, almost all non-clinical opioid use has been scored at the scale of approval in virtually every social institution. However, in the UK, the 1926 report of the Department Committee on Morphine and Heroin Dependence under the Leadership of the Royal College of Physicians reaffirmed medical control and established the "British control system" - which lasted until the 1960s; in the US, the Law on Controlled Supervision in 1970 significantly loosened the severity of the Harrison Act.

Before the 20th century, institutional approval was often higher, even in Europe and America. In some cultures, opioid approval is significantly higher than alcohol approval. Opiates were used to treat depression and anxiety until the mid-1950s.

src: www.healthline.com

Society and culture

Definition

The term "opioid" originated in the 1950s. It combines "opium" "-oid" meaning "opiate-like" ("opiates" is morphine and similar drugs derived from opium). The first scientific publication to use it, in 1963, included a footnote which states, "In this paper, the term, 'opioid', is used in the sense originally proposed by George H. Acheson (personal communication) to refer to any chemical compound. with activities such as morphine ". In the late 1960s, the study found that opiate effects were mediated by the activation of specific molecular receptors in the nervous system, called "opioid receptors". The definition of "opioid" is then refined to refer to a substance having morphine-like activity mediated by activation of opioid receptors. A modern pharmacological textbook states: "the term opioid applies to all agonists and antagonists with activities such as morphine, as well as synthetic opioid peptides that occur naturally." Other pharmacological references eliminate the requirement of morphine-like : "Opioid, a more modern term, is used to designate all substances, both natural and synthetic, which bind opioid receptors (including antagonists)". Some sources define the term opioid to exclude opiates , and others use opiate comprehensively than opioid , but opioids used inclusively are considered modern, liked and widely used.

Efforts to reduce abuse in the US

In 2011, the Obama administration released a white paper describing the government's plans to tackle the opioid crisis. Administrative concerns about addictions and accidental overdoses have been voiced by many medical and other government advisory groups around the world.

By 2015, prescription drug monitoring programs exist in every state except one. These programs allow pharmacists and recipes to access the patient's prescription history to identify suspicious uses. However, a US physician survey published in 2015 found that only 53% of physicians use this program, while 22% are unaware that the program is available to them. The Centers for Disease Control and Prevention assigned to establish and publish new guidelines, and to be lobbied a great deal. In 2016, the United States Centers for Disease Control and Prevention published a Guide to Opioid Prescription for Chronic Pain, recommending that opioids be used only when the benefits for pain and function are expected to outweigh risks, and then used at the lowest effective dose, by avoiding the use of opioids and benzodiazepines together if possible. Research has also shown that automated algorithms may be able to identify patients requiring more intensive screening and/or interventions for the use of non-medical opioids; However, there is no standard for determining the use of non-medical opioids, and some algorithms have not yet been applied to real-world settings.

On August 10, 2017, Donald Trump declared an opioid crisis (non-FEMA) national public health emergency.

Global deficiency

Morphine and other poppy-based drugs have been identified by the World Health Organization as important in the treatment of severe illness. In 2002, seven countries (US, UK, Italy, Australia, France, Spain, and Japan) used 77% of the world's morphine supply, leaving many developing countries lacking painkillers. The current supply system of opium feedstocks for making poppy-based drugs is regulated by the International Narcotics Control Board under the provisions of the 1961 Single Convention on Narcotics Drugs. The amount of raw poppy raw materials each country can ask for each year under this provision shall be in accordance with the nation's forecast taken from national consumption in the preceding two years. In many countries, underrescription of morphine is rampant due to high prices and lack of training in poppy-based prescription drugs. The World Health Organization now works with the administration of various countries to train health workers and to develop national regulations on prescribing medicines to facilitate larger poppy-based prescription drugs.

Another idea to increase morphine availability is proposed by the Senlis Council, which suggests, through their proposal to Afghanistan Morfin, that Afghanistan can provide cheaper pain relief solutions to developing countries as part of a second tier supply system that will complement current INCB. systems that are regulated by keeping the balance and closed system set while providing morphine finished products for those who are severely ill and unable to access poppy-based drugs under the current system.

Use of recreation

Opioids can produce strong feelings of euphoria and are often used in recreation. Traditionally associated with dark opioids such as heroin, prescription opioids are misused recreationally.

Drug abuse and non-medical use include the use of drugs for reasons or doses other than those specified. Opioid injections may also include administering drugs to people who are not prescribed. Such transfers can be treated as crimes, punishable by imprisonment in many countries. By 2014, nearly 2 million Americans are abused or dependent on prescribed opioids.

src: hankjohnson.house.gov

Classification

There are a number of broad opioid classes:

• Natural opiate: alkaloid contained in opium poppy resin, especially morphine, codeine, and thebaine, but not papaverine and noscapine which have different mechanisms of action; The following can be thought of as a natural opiate: Leaves of Mitragyna speciosa (also known as kratom) contain several natural opioids, active through Mu- and Delta receptors. Salvinorin A, found naturally in the Salvia divinorum plant, is a kappa-opioid receptor agonist.
<3> Esters of opio morphine: slightly altered chemically but more naturally than semi-synthetic, because most are prodrug morphine, diacetylmorphine (nicotine morphine, nicotine), dipropanoylmorphine (dipropionate morphine), desomorphine, acetylpropionylmorphine , dibenzoylmorphine, diacetyldihydromorphine;
• Semi-synthetic opioids: made either from natural opioid or morphine ester, such as hydromorphone, hydrocodone, oxycodone, oximeter, ethylmorphine and buprenorphine;
• Fully synthetic opioids: such as fentanyl, pethidine, levorphanol, methadone, tramadol, tapentadol, and dextropropoxyphene;
• Endogenous opioid peptides, produced naturally in the body, such as endorphins, enkephalins, dynorphins, and endomorphins. Morphine, and several other opioids, produced in small quantities in the body, fall into this category.

Tramadol and tapentadol, which act as monoamine absorption inhibitors also act as mild and powerful agonists (respectively) of the -opioid receptors. Both drugs produce analgesia even when naloxone, an opioid antagonist, is administered.

Some small opium alkaloids and various substances with opioid action are also found elsewhere, including molecules present in the kratom, corydalis , and salvia divinorum plants and some poppy species other than < i> Papaver somniferum . There are also strains that produce an enormous amount of thebaine, an essential ingredient for making synthetic and synthetic semi-opioids. Of all the more than 120 species of poppy, only two produce morphine.

Among the analgesics there are a small number of agents acting on the central nervous system but not on the opioid receptor system and therefore have no other opioid qualities although they can produce euphoria by relieving pain - euphoria which, as it is produced, does not form basic habituation, physical dependence, or addiction. Most important of these are nephopam, orphenadrine, and possibly phenyltoloxamine or some other antihistamine. Tricyclic antidepressants have pain-relieving effects as well, but they think to do so by indirectly activating endogenous opioid systems. Paracetamol is dominated by a central (non-narcotic) work analgesic that mediates its effect with action on the decreased serotoninergic pathway (5-hydroxy triptaminergic), to promote 5-HT release (which inhibits pain mediator release). It also decreases the activity of cyclo-oxygenase. It has recently been found that most or all of the therapeutic efficacy of paracetamol is due to the metabolite, AM404, which increases serotonin release and inhibits the absorption of anandamide.

Other analgesics work peripherally ( i.e. , not in the brain or spinal cord). Research begins to show that morphine and related drugs may indeed have peripheral effects as well, such as morphine gel that acts on burns. Recent investigations have found opioid receptors in peripheral sensory neurons. A significant fraction (up to 60%) of opioid analgesia may be mediated by such peripheral opioid receptors, especially in inflammatory conditions such as arthritis, traumatic pain or surgery. Inflammatory pain is also smoothed by endogenous opioid peptides that activate peripheral opioid receptors.

It was discovered in 1953 that humans and some animals naturally produce minute morphine, codeine, and possibly some simpler derivatives such as heroin and dihydromorphine, in addition to endogenous opioid peptides. Some bacteria are capable of producing some semi-synthetic opioids such as hydromorphone and hydrocodone while living in solutions containing morphine or codeine respectively.

Many alkaloids and other derivatives of opium poppy are not opioids or narcotics; the best example is papaverine relaxed smooth muscle. Noscapine is a marginal case because it has a CNS effect but is not always the same as morphine, and may be in its own category.

Dextromethorphan (stereoisomer levomethorphan, semi-synthetic opioid agonist) and its dextrorphan metabolites have no opioid analgesic effect at all despite their structural similarity to other opioids; instead they are potent NMDA antagonists and sigma-1 and 2-receptor agonists and are used in many free-selling cough suppressants.

Salvinorin A is a unique and powerful selective receptor agonist. It is not considered opioid well, because:

1. chemically, it is not an alkaloid; and
2. has no typical opioid properties: there is absolutely no ansiolytic effect or cough suppressant. This is not a strong hallucinogen.

Endogenous opioids

Opioid peptides produced in the body include:

? -endorphin is expressed in Pro-opiomelanocortin (POMC) cells in the arcuate nucleus, in the brain stem and immune cells, and acts through the -opioid receptors. ? -endorphine has many effects, including on sexual behavior and appetite. ? -endorphin is also secreted into the circulation of corticotropes and pituitary melanotropes. ? -neo-endorphin is also expressed in POMC cells in the arcuate nucleus.

met-enkephalin is widespread in CNS and in immune cells; [met] -enkephalin is the product of the proenkephalin gene, and acts through? and -opioid receptors. leu-enkephalin, also a product of the proenkephalin gene, acts through the -opioid receptors.

Dynorphin acts through the -opioid receptors, and is widely distributed on CNS, including in the spinal cord and hypothalamus, including especially arcuate nuclei and in both oxytocin and vasopressin neurons in the supraoptic nucleus.

Endomorphin works through the -opioid receptors, and is stronger than other endogenous opioids in these receptors.

Opium alkaloids and their derivatives

Opium alkaloids

Phenanthrenes naturally in (opium):

Persiapan alkaloid opium campuran, termasuk papaveretum, kadang-kadang masih digunakan.

Ester morfin

Eter morfin

Turunan alkaloid semi-sintetis

Opioid sintetis

Anilidopiperidines

Phenylpiperidines

Turunan Diphenylpropylamine

Turunan Benzomorphan

Turunan Oripavine

Turunan Morfinan

Lainnya

Modulator alosterik

Plain allosteric modulators do not belong to opioids, but are classified as opioidergic.

opioid antagonists

Opioid table

Table opioid morphinan

Non-morphinan opioid table

src: hankjohnson.house.gov

See also

• Froehde Reagent
• Comparison of Opusions
• Opioid epidemic

src: s.newsweek.com

References

src: www.healthline.com

External links

• Symptoms of Opioid Withdrawal - Information on Opioids and Opiate Withdrawal Problems
• World Health Organization guidelines for availability and accessibility of controlled substances
• CDC Guidelines for Opioid Prescription for Chronic Pain - USA, 2016
• List of references to previous publications
• Link to all language versions of previous publications
• Video: Opioid Side Effects (Vimeo) (YouTube) - A short education film about the practical management of opioid side effects.

Source of the article : Wikipedia