Opiate

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Harvesting the poppy pod. Harvesting opium.jpg
Harvesting the poppy pod.
A chart outlining the structural features that define opiates and opioids, including distinctions between semi-synthetic and fully synthetic opiate structures Opiates v opioids.png
A chart outlining the structural features that define opiates and opioids, including distinctions between semi-synthetic and fully synthetic opiate structures

An opiate is an alkaloid substance derived from opium (or poppy straw). [1] It differs from the similar term opioid in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonists). [2] Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum . [3] The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions, with evidence of opiate trade and use for pain relief as early as the eighth century AD. [4] Most opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.

Contents

In 2014, between 13 and 20 million people used opioids recreationally (0.3% to 0.4% of the global population between the ages of 15 and 65). [5] According to the CDC, from this population, there were 47,000 deaths, with a total of 500,000 deaths from 2000 to 2014. [6] In 2016, the World Health Organization reported that 27 million people suffer from opioid use disorder. They also reported that in 2015, 450,000 people died as a result of drug use, with between a third and a half of that number being attributed to opioids. [7]

Overview

Codeine Codein - Codeine.svg
Codeine
Chemical structure of morphine Morphin - Morphine.svg
Chemical structure of morphine

Opiates belong to the large biosynthetic group of benzylisoquinoline alkaloids, and are so named because they are naturally occurring alkaloids found in the opium poppy. The major psychoactive opiates are morphine, codeine, and thebaine. Papaverine, noscapine, and approximately 24 other alkaloids are also present in opium but have little to no effect on the human central nervous system. Alkaloids that have no effect on the central nervous system were not always considered to be opiates, but current trend is to refer to all alkaloids derived from opium or poppy straw as such. Very small quantities of hydrocodone and hydromorphone are detected in assays of opium on rare occasions; it appears to be produced by the plant under circumstances and by processes that are not understood at this time.[ citation needed ] Dihydrocodeine, oxymorphol, oxycodone, oxymorphone, metopon Possibly other derivatives of morphine and/or hydromorphone also are found in trace amounts in opium.[ citation needed ]

Despite morphine being the most medically significant opioid, larger quantities of codeine are consumed medically, most of it synthesized from morphine. Codeine has greater and more predictable oral bioavailability. Codeine is not reliably metabolised into its active form, morphine, by CYP2D6 due to the considerable amount of polymorphism. Many individuals lack any appreciable metabolism to morphine and experience no therapeutic effects (although may still have nausea/vomiting or constipation). A significant population are rapid, or ultra-rapid metabolizers and can quickly develop fatal toxicity from even the small amount present in breast milk or from a few doses. It is widely thought that Codeine has less abuse potential than morphine, in spite of widely being abused. Its abuse potential is largely limited by its adverse effect profile. [8] Use of codeine in many countries is decreasing because of the wide range of metabolism, frequent adverse effects at therapeutic (30 to 60mg doses) doses, and in most people its analgesic efficacy is comparable to a therapeutic dose of acetaminophen.

Morphine addiction cure advertisement in the year 1900 MorphineAdvertisement1900 - no watermark.JPG
Morphine addiction cure advertisement in the year 1900

Opiate withdrawal syndrome effects are associated with the abrupt cessation or reduction of prolonged opiate usage.

The manifestation of opiate dependence and abuse relies on a variety of factors, including the opiate's pharmacokinetic properties and the user's predisposition for addiction. [9]

Synthesis

While the full synthesis of opioids from naphthoquinone (Gates synthesis) or other simple organic starting materials is possible, they are tedious and uneconomical processes. Therefore, most of the opiate-type analgesics in use today are either extracted from Papaver somniferum or synthesized from those opiates, especially thebaine. [10]

In 2015 researchers reported successful biosynthesis of thebaine and hydrocodone using genetically modified yeast. Once scaled for commercial use, the process would cut production time from a year to several days and could reduce costs by 90%. [11] [12]

Pharmacokinetics

Codeine

Codeine is a prodrug which is converted to morphine and acts on μ-opiate receptors. It is converted to morphine by metabolism of CYP2D6 enzymes. Individuals who have lower CYP2D6 activity may not metabolize codeine at all, and will not experience its analgesic effects. Conversely, individuals with rapid or ultra-rapid CYP2D6 activity may metabolize the drug too quickly and experience dose-related side effects such as sedation and fatal respiratory depression. [13]

Fentanyl

Fentanyl is a synthetic piperidine opioid structurally similar to arylpiperidines. It is a strong μ-receptor agonist that is 80–100 times more potent than morphine, and has a fast onset with a shorter duration of action than morphine due to redistribution from CNS location to fatty tissue. When it is used as a continual drug (e.g. transdermal patches, longer term use of IV fentanyl in ICU patients) its elimination half-life and duration of effect are longer than morphine. It is metabolized in the liver by CYP3A4 enzymes to the compound norfentanyl. [14]

Heroin

Global estimates of drug users in 2016
(in millions of users) [15]
SubstanceBest
estimate		Low
estimate		High
estimate
Amphetamine-
type stimulants 		34.1613.4255.24
Cannabis 192.15165.76234.06
Cocaine 18.2013.8722.85
Ecstasy 20.578.9932.34
Opiates 19.3813.8026.15
Opioids 34.2627.0144.54

Heroin, the common name for diacetylmorphine, is the first of several semi-synthetic opioids to be derived from morphine, a component of natural opium. [16] It is formed by the acetylation of morphine in order to increase the lipid solubility. [17] Heroin (diacetylmorphine) is a morphine prodrug; it is metabolized by the liver into morphine after administration. One of the major metabolites of heroin, 6-monoacetylmorphine (6-MAM), is also a morphine prodrug.

Hydromorphone

Hydromorphone is derived from morphine and may be used as an alternative to it. It has a high first-pass metabolism when given orally, and is primarily glucuronidated in the liver to hydromorphone-3-glucoronide (H3G). 75% of hydromorphone is renally excreted, with 7% excreted as the parent opiate. [14]

Meperidine

Meperidine is a synthetic opiate, part of the arylpiperidine class. It is a strong μ-receptor agonist with 1/10th the potency of morphine. It has historically also been used to treat rigors, and has a half-life of three to four hours. It is hepatically metabolized to the active metabolites of normeperidine, normepiridinic acid, and medperidinic acid. Normeperidine may accumulate to toxic levels in patients with renal impairment with repeated doses, and can cause CNS excitation and seizures. [14]

Methadone

Methadone has a higher bioavailability and half-life compared to morphine. [18] It is metabolized to an inactive product by N-demethylation by CYP3A4 enzymes in the liver. It has high person-to-person variability because of varying levels of CYP3A4 in individuals. [19] It is approved for treatment of moderate to severe pain as well as opioid dependence. [20] Because of its high risk of drug interactions, liver toxicity, and patient variability, patients have to be monitored closely at methadone clinics. [21] In addition, there is an increase risk of mortality in patients who are treated with methadone compared to other opioids, thought to be due to QTc prolongation and cardiac arrhythmias.

Morphine

Nicomorphine (Vilan, morphine dinicotinate), Diamorphine (Heroin, morphine diacetate), dipropanoylmorphine (morphine dipropionate), desomorphine (Permonid, di-hydro-desoxy-morphine), methyldesorphine, acetylpropionylmorphine, dibenzoylmorphine, diacetyldihydromorphine, and several others are also derived from morphine. [22]

Morphine is metabolized in the liver to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), and are excreted by the kidneys. It is are also able to cross into the blood-brain barrier into the cerebrospinal fluid. M6G has potent analgesic activity, binds to opioid receptors, and is a main contributor to the therapeutic benefit of morphine. [23] M3G does not act as an analgesic, has a low affinity for opioid receptors, and may possibly antagonize the therapeutic effects of morphine and M6G. Moreover, high doses of morphine, and thus M3G, are associated with neurotoxic side effects such as hyperalgesia, allodynia and myoclonus. [24]

Oxymorphone

Oxymorphone is a congener of morphine. It is metabolized to 6-hydroxy-oxymorphone and oxymorphone-3-glucuronide, and 40% is excreted as metabolites. 6-hydroxy-oxymorphine is active and exists in a 1:1 ratio with the parent drug. Oxymorphone-3-glucuronide's activity is unknown. [14]

Indication

Opiates with opioid activity are mainly used for pain management with the premise that there will be benefits for both pain & function that will outweigh the risks to the patient. [25] Another indication is symptomatic relief of shortage of breath, both in the acute setting (for example, pulmonary edema) and in terminally ill patients. [26] [27]

In spite of scarce, often conflicting, evidence, at times studies showing no benefit at all, opioids such as codeine, hydrocodone, and hydromorphone have been traditionally used for treatment of acute viral cough (aka "acute bronchitis"), cough due to COPD exacerbation, chronic post-viral cough, chronic idiopathic cough, and cough from other causes. Given the abuse potential, the frequent GI side effects, and several studies showing no discernable benefit, recommendations are against use of opioids for cough in children. In spite of widespread use, the science supporting use of opioids for cough in adults is most notable for the small sample size, poor study design, and inconclusive results which suggest that there may be a small reduction in the amount of coughing when it is precisely measured. Actual evidence of patient-oriented outcomes (e.g. do the patients feel any better than when given a placebo) is elusive, and the use of codeine as the "gold-standard" for which other drugs can be compared has been called into question (as showing that a drug is as good as, or at least not worse than, a drug with no benefit and only noxious side effects and a potential for abuse leaves much to be desired).[ citation needed ]

Opioid dose conversions may be necessary when switching medications given the differing pharmacodynamics between opioids. Generally, parenteral (IV or IM) morphine is used as the standard for converting between opiates to achieve equivalent analgesic effects. These differences in morphine-equivalents may differ between formulations of the same medication, and certainly between oral and injection. [28] Calculating total daily dose using morphine milligram equivalents is used to identify patients at risk of overdose. [29]

Complications and side effects

Common side effects associated with opioid use include: sedation, nausea, dizziness, vomiting, constipation, physical dependence, tolerance, and potentially fatal respiratory depression. Of these the most common are constipation & nausea. There is no development of tolerance to constipation. [30] This is why stool softeners or laxatives (polyethylene glycol, docusate, and senna) are often prescribed with opioids. [31]

While overdose, whether intentional, accidental, or due to rapid 2D6 conversion of codeine (or tramadol, a non-opiate opioid that, like codeine, has little intrinsic effect on μ-receptors, but rather acts as pro-drug with an active metabolite that is a μ-agonist.

Less common side effects include: delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction (hypogonadism is often seen in men taking chronic opioids, but is not always clinically evident), muscle rigidity, and myoclonus. [32]

Opiate use for pain is widely accepted in the healthcare system. However, long-term treatment for chronic pain is controversial as there is a high risk of addiction associated with its use leading to abuse and diversion to others even when taken properly. [33] Those addicted to opiates will prioritize acquiring these drugs over other activities in their lives, negatively impacting their professional and personal relationships. Moreover, there are not many well-designed studies evaluating the overall safety and efficacy. Many small studies using small doses (often half the recommended dose) have not shown much effect, but these cannot be relied upon to give much information on the more common practice of step-wise therapy and slow dose escalation.

Chronic opioid use predictably leads to tolerance, and may do so fairly quickly (days to weeks). This occurs even with what are considered modest doses (e.g. ≥25mg oxycodone a day). This may result in the patient to need higher and/or more frequent doses of the drug to get euphoric effects, although it may not be a factor in analgesic effects as tolerance to a dose of opioid does not seem related to loss of efficacy. [34] Tolerance is associated with upregulation of μ-receptors (and possibly others).

Concentration-dependence adverse effects may vary based on the user's genetic polymorphisms which can alter drug metabolism. Cytochrome P450 (notably CYP2D6, but also CYP3A4) is responsible for the metabolism of various opiates to active metabolites and variations in CYP450 activity lead to varying serum drug levels. [35]

Pharmacology in pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is an essential defensive function where pain works as an alarm to avoid or limit tissue damage. Its neurobiology is complex, and involves stimulation of several different types of nerves. Opioids act upon opioid receptors that are coupled to inhibitor G protein coupled receptors (GPCR). These receptors fall into 3 classes: μ (mu), δ (delta), and κ (kappa) receptors. [36]

More than 70% of opioid receptors are μ receptors, predominantly located on the central terminals of nociceptors in the dorsal horn of the spinal cord. The remaining 30% of opioid receptors are located post-synaptically on dendrites of second-order spinothalamic neurons & interneurons. [36]

When an opiate binds as an agonist to the GPCR, there will be a signaling cascade resulting in the inhibition of adenylate cyclase and calcium ion channels with the stimulation of potassium ion channels. The net effect of these changes is a reduced intracellular cAMP and hyperpolarization of the neuronal cell reducing neurotransmitter release. [37] Through this pathway, when opiates bind to and activate the mu receptor, there is a decrease transmission of pain signalling. This pathway targeted for the analgesia properties that opiates are known and used for. Other clinically important roles of mu are its involvement in respiratory and cardiovascular functions, gastrointestinal peristalsis, feeding, and mood. [38] These other pathways are important because they explain the side effects of opiate use like respiratory depression at high doses, constipation with chronic use, and addicting properties. [32]

Absolute contraindications

Those with the following conditions should not be using opioids: [39]

Risk factors for prescription abuse

The following are risk factors for opiate prescription abuse: [40]

Statistically, middle-aged patients with substance use history and psychiatric comorbidities are seen with higher mortality risks such as suicide.

Iatrogenic physiological and psychological drug dependence can occur to one of any background. Some physicians are more liberal with their prescribing of opiates and their patients become dependent on opiates by simply following their doctor's orders. [41]

See also

Related Research Articles

<span class="mw-page-title-main">Heroin</span> Opioid used as an analgesic and a recreational drug for its euphoric effects

Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the dried latex of the Papaver somniferum plant; it is mainly used as a recreational drug for its euphoric effects. Medical-grade diamorphine is used as a pure hydrochloride salt. Various white and brown powders sold illegally around the world as heroin are routinely diluted with cutting agents. Black tar heroin is a variable admixture of morphine derivatives—predominantly 6-MAM (6-monoacetylmorphine), which is the result of crude acetylation during clandestine production of street heroin. Heroin is used medically in several countries to relieve pain, such as during childbirth or a heart attack, as well as in opioid replacement therapy.

<span class="mw-page-title-main">Hydrocodone</span> Opioid drug used in pain relief

Hydrocodone, also known as dihydrocodeinone, is a semisynthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug: in the United States a Schedule II Controlled Substance.

<span class="mw-page-title-main">Morphine</span> Pain medication of the opiate family

Morphine is a strong opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies. It is mainly used as an analgesic. There are numerous methods used to administer morphine: oral; sublingual; via inhalation; injection into a muscle, injection under the skin, or injection into the spinal cord area; transdermal; or via rectal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine are available as MS-Contin, Kadian, and other brand names as well as generically.

<span class="mw-page-title-main">Methadone</span> Opioid medication

Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid use disorder. It is used to treat chronic pain, and it is also used to treat addiction to heroin or other opioids. Prescribed for daily use, the medicine relieves cravings and removes withdrawal symptoms. Withdrawal management using methadone can be accomplished in less than a month, or it may be done gradually over a longer period of time, or simply maintained for the rest of the patient's life. While a single dose has a rapid effect, maximum effect can take up to five days of use. After long-term use, in people with normal liver function, effects last 8 to 36 hours. Methadone is usually taken by mouth and rarely by injection into a muscle or vein.

<span class="mw-page-title-main">Oxycodone</span> Opioid medication

Oxycodone, sold under various brand names such as Roxicodone and OxyContin, is a semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and is a commonly abused drug. It is usually taken by mouth, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection. Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, naltrexone, and aspirin.

<span class="mw-page-title-main">Thebaine</span> Opiate alkaloid constituent of opium

Thebaine (paramorphine), also known as codeine methyl enol ether, is an opiate alkaloid, its name coming from the Greek Θῆβαι, Thēbai (Thebes), an ancient city in Upper Egypt. A minor constituent of opium, thebaine is chemically similar to both morphine and codeine, but has stimulatory rather than depressant effects. At high doses, it causes convulsions similar to strychnine poisoning. The synthetic enantiomer (+)-thebaine does show analgesic effects apparently mediated through opioid receptors, unlike the inactive natural enantiomer (−)-thebaine. While thebaine is not used therapeutically, it is the main alkaloid extracted from Papaver bracteatum and can be converted industrially into a variety of compounds, including hydrocodone, hydromorphone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine, butorphanol and etorphine.

<span class="mw-page-title-main">Narcotic</span> Chemical substance with psycho-active properties

The term narcotic originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates and opioids, commonly morphine and heroin, as well as derivatives of many of the compounds found within raw opium latex. The primary three are morphine, codeine, and thebaine.

<span class="mw-page-title-main">Tramadol</span> Medication of the opioid type

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Hydromorphone</span> Opioid medication used for pain relief

Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is a morphinan opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mouth or by injection into a vein, muscle, or under the skin. Effects generally begin within half an hour and last for up to five hours. A 2016 Cochrane review found little difference in benefit between hydromorphone and other opioids for cancer pain.

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work in the brain to produce a variety of effects, including pain relief. As a class of substances, they act on opioid receptors to produce morphine-like effects.

<span class="mw-page-title-main">Dihydrocodeine</span> Opioid

Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) or aspirin. It was developed in Germany in 1908 and first marketed in 1911.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

Opioid-induced hyperalgesia (OIH) or opioid-induced abnormal pain sensitivity, also called paradoxical hyperalgesia, is an uncommon condition of generalized pain caused by the long-term use of high dosages of opioids such as morphine, oxycodone, and methadone. OIH is not necessarily confined to the original affected site. This means that if the person was originally taking opioids due to lower back pain, when OIH appears, the person may experience pain in the entire body, instead of just in the lower back. Over time, individuals taking opioids can also develop an increasing sensitivity to noxious stimuli, even evolving a painful response to previously non-noxious stimuli (allodynia). This means that if the person originally felt pain from twisting or from sitting too long, the person might now additionally experience pain from a light touch or from raindrops falling on the skin.

<span class="mw-page-title-main">Thebacon</span> Opioid medication

Thebacon, or dihydrocodeinone enol acetate, is a semisynthetic opioid that is similar to hydrocodone and is most commonly synthesised from thebaine. Thebacon was invented in Germany in 1924, four years after the first synthesis of hydrocodone. Thebacon is a derivative of acetyldihydrocodeine, where only the 6–7 double bond is saturated. Thebacon is marketed as its hydrochloride salt under the trade name Acedicon, and as its bitartrate under Diacodin and other trade names. The hydrochloride salt has a free base conversion ratio of 0.846. Other salts used in research and other settings include thebacon's phosphate, hydrobromide, citrate, hydroiodide, and sulfate.

<span class="mw-page-title-main">Codeine</span> Opiate and prodrug of morphine used to treat pain

Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, Papaver somniferum. It is typically used to treat mild to moderate degrees of pain. Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Evidence does not support its use for acute cough suppression in children or adults. In Europe, it is not recommended as a cough medicine in those under 12 years of age. It is generally taken by mouth. It typically starts working after half an hour, with maximum effect at two hours. Its effects last for about four to six hours. Codeine exhibits abuse potential similar to other opioid medications, including a risk of habituation and overdose.

<span class="mw-page-title-main">Tapentadol</span> Opioid analgesic of benzenoid class

Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.

<span class="mw-page-title-main">Phenazocine</span> Opioid analgesic

Phenazocine is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

<span class="mw-page-title-main">Opioid overdose</span> Medical condition

An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that can cause hypoxia from slow and shallow breathing. Other symptoms include small pupils, and unconsciousness; however, its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.

Clinical Opiate Withdrawal Scale (COWS) is a method used by registered practitioners to measure the severity of a patient's opioid withdrawal symptoms. This method consists of a series of 11 topics each comprising 4 - 5 common symptoms experienced by a patient undergoing opioid withdrawal. In each topic a rank is given depending on what the patient responds to. Generally, 0 is considered to be no symptom shown and 4 or 5 is considered to be the most common and severe symptom shown. These results are then added up and a final diagnosis is made based on the value obtained. This test is crucial as it allows the practitioner to assess the physiological and psychological behaviours of the patient as well as the severity of each symptom during the duration of the examination. The results are grouped into 3 categories of mild, moderately severe and severe. Mild consists of 5 to 12 points, moderately severe consists of 13 to 24 points and anything above 36 points is severe and requires direct medical attention.

References

  1. ↑ "Definition of OPIOID". www.merriam-webster.com. 2023-11-06. Retrieved 2023-11-11.
  2. ↑ Hemmings, Hugh C.; Egan, Talmage D. (2014). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print. Elsevier Health Sciences. p. 253. ISBN   978-1437716795. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. It has been used in the past to refer to drugs with opium-like effects, but that use is dated. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists).
  3. ↑ "Opiate - Definitions from Dictionary.com". dictionary.reference.com. Retrieved 2008-07-04.
  4. ↑ Brownstein, M J (1993-06-15). "A brief history of opiates, opioid peptides, and opioid receptors". Proceedings of the National Academy of Sciences of the United States of America. 90 (12): 5391–5393. Bibcode:1993PNAS...90.5391B. doi: 10.1073/pnas.90.12.5391 . ISSN   0027-8424. PMC   46725 . PMID   8390660.
  5. ↑ "Status and Trend Analysis of Illict[sic] Drug Markets" (PDF). World Drug Report 2015. Retrieved 26 June 2015.
  6. ↑ "CDC Press Releases". CDC. 2016-01-01. Retrieved 2019-10-17.
  7. ↑ "WHO | Information sheet on opioid overdose". WHO. Retrieved 2019-10-21.
  8. ↑ "Canadian Guideline for Opioid Use for Pain — Appendix B-8: Opioid Conversion and Brand Availability in Canada". nationalpaincentre.mcmaster.ca. Retrieved 2016-04-18.
  9. ↑ Gruber, Staci A.; Silveri, Marisa M.; Yurgelun-Todd, Deborah A. (2007-09-01). "Neuropsychological Consequences of Opiate Use". Neuropsychology Review. 17 (3): 299–315. doi:10.1007/s11065-007-9041-y. ISSN   1573-6660. PMID   17690984. S2CID   22057898.
  10. ↑ Synthesis of morphine alkaloids Presentation School of Chemical Sciences, University of Illinois at Urbana-Champaign Archived 2013-02-28 at the Wayback Machine retrieved 12-02-2010
  11. ↑ Galanie, Stephanie; Thodey, Kate; Trenchard, Isis J.; Interrante, Maria Filsinger; Smolke, Christina D. (2015-09-04). "Complete biosynthesis of opioids in yeast". Science. 349 (6252): 1095–1100. Bibcode:2015Sci...349.1095G. doi:10.1126/science.aac9373. ISSN   0036-8075. PMC   4924617 . PMID   26272907.
  12. ↑ Mobley, Emily (2015-08-13). "Yeast cells genetically modified to create morphine-like painkiller". The Guardian. ISSN   0261-3077 . Retrieved 2016-04-17.
  13. ↑ Kirchheiner, J.; Schmidt, H.; Tzvetkov, M.; Keulen, J.-Tha; Lötsch, J.; Roots, I.; Brockmöller, J. (August 2007). "Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication". The Pharmacogenomics Journal. 7 (4): 257–265. doi:10.1038/sj.tpj.6500406. ISSN   1473-1150. PMID   16819548. S2CID   6662662.
  14. 1 2 3 4 Inturrisi, Charles E. (July 2002). "Clinical pharmacology of opioids for pain". The Clinical Journal of Pain. 18 (4 Suppl): S3–13. CiteSeerX   10.1.1.326.4737 . doi:10.1097/00002508-200207001-00002. ISSN   0749-8047. PMID   12479250. S2CID   17984040.
  15. ↑ "Annual prevalence of use of drugs, by region and globally, 2016". World Drug Report 2018. United Nations Office on Drugs and Crime. 2018. Retrieved 7 July 2018.
  16. ↑ Copeland, CS (Jul–Aug 2014). "The Human Side of the Heroin Epidemic" (PDF). Healthcare Journal of New Orleans.
  17. ↑ "Heroin drug profile | www.emcdda.europa.eu". www.emcdda.europa.eu. Retrieved 2023-12-18.
  18. ↑ Grissinger, Matthew (August 2011). "Keeping Patients Safe From Methadone Overdoses". Pharmacy and Therapeutics. 36 (8): 462–466. ISSN   1052-1372. PMC   3171821 . PMID   21935293.
  19. ↑ Ferrari, Anna; Coccia, Ciro Pio Rosario; Bertolini, Alfio; Sternieri, Emilio (December 2004). "Methadone--metabolism, pharmacokinetics and interactions". Pharmacological Research. 50 (6): 551–559. doi:10.1016/j.phrs.2004.05.002. ISSN   1043-6618. PMID   15501692.
  20. ↑ Anderson, Ilene B; Kearney, Thomas E (January 2000). "Use of methadone". Western Journal of Medicine. 172 (1): 43–46. doi:10.1136/ewjm.172.1.43. ISSN   0093-0415. PMC   1070723 . PMID   10695444.
  21. ↑ Lugo, Ralph A.; Satterfield, Kristin L.; Kern, Steven E. (2005). "Pharmacokinetics of methadone". Journal of Pain & Palliative Care Pharmacotherapy. 19 (4): 13–24. doi:10.1080/J354v19n04_05. ISSN   1536-0288. PMID   16431829. S2CID   29509469.
  22. ↑ "Esters of Morphine". www.unodc.org. United Nations Office on Drugs and Crime. Retrieved 10 March 2012.
  23. ↑ Christrup, L. L. (January 1997). "Morphine metabolites". Acta Anaesthesiologica Scandinavica. 41 (1): 116–122. doi:10.1111/j.1399-6576.1997.tb04625.x. PMID   9061094. S2CID   9858042.
  24. ↑ Andersen, Gertrud; Christrup, Lona; Sjøgren, Per (January 2003). "Relationships among morphine metabolism, pain and side effects during long-term treatment: an update". Journal of Pain and Symptom Management. 25 (1): 74–91. doi: 10.1016/s0885-3924(02)00531-6 . ISSN   0885-3924. PMID   12565191.
  25. ↑ Cohen, Brandon; Preuss, Charles V. (2019), "Opioid Analgesics", StatPearls, StatPearls Publishing, PMID   29083658 , retrieved 2019-10-31
  26. ↑ Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS; et al. (2016). "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC". Eur Heart J. 37 (27): 2129–2200. doi: 10.1093/eurheartj/ehw128 . PMID   27206819.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ↑ Albert RH (2017). "End-of-Life Care: Managing Common Symptoms". Am Fam Physician. 95 (6): 356–361. PMID   28318209.
  28. ↑ Patanwala, Asad E; Duby, Jeremiah; Waters, Dustin; Erstad, Brian L (2007-02-01). "Opioid Conversions in Acute Care". Annals of Pharmacotherapy. 41 (2): 255–267. doi:10.1345/aph.1H421. ISSN   1060-0280. PMID   17299011. S2CID   2684749.
  29. ↑ "Morphine Equivalent Units/Morphine Milligram Equivalents". www.asam.org. Archived from the original on 2021-10-19. Retrieved 2019-11-10.
  30. ↑ Benyamin, Ramsin; Trescot, Andrea M.; Datta, Sukdeb; Buenaventura, Ricardo; Adlaka, Rajive; Sehgal, Nalini; Glaser, Scott E.; Vallejo, Ricardo (2008). "Opioid complications and side effects". Pain Physician. 11 (2 Suppl): S105–120. doi: 10.36076/ppj.2008/11/S105 . ISSN   1533-3159. PMID   18443635.
  31. ↑ Publishing, Harvard Health (27 September 2018). "Pain relief, opioids, and constipation". Harvard Health. Retrieved 2019-10-24.
  32. 1 2 Benyamin, Ramsin; Trescot, Andrea M.; Datta, Sukdeb; Buenaventura, Ricardo; Adlaka, Rajive; Sehgal, Nalini; Glaser, Scott E.; Vallejo, Ricardo (March 2008). "Opioid complications and side effects". Pain Physician. 11 (2 Suppl): S105–120. doi: 10.36076/ppj.2008/11/S105 . ISSN   1533-3159. PMID   18443635.
  33. ↑ Reference, Genetics Home. "Opioid addiction". Genetics Home Reference. Retrieved 2019-10-24.
  34. ↑ Abuse, National Institute on Drug. "Prescription Opioids". www.drugabuse.gov. Retrieved 2019-10-24.
  35. ↑ Foster, Adriana; Mobley, Elizabeth; Wang, Zixuan (2007). "Complicated Pain Management in a CYP450 2D6 Poor Metabolizer". Pain Practice. 7 (4): 352–356. doi:10.1111/j.1533-2500.2007.00153.x. ISSN   1533-2500. PMID   17986163. S2CID   30624022.
  36. 1 2 Fornasari, Diego (2014). "Pain pharmacology: focus on opioids". Clinical Cases in Mineral and Bone Metabolism. 11 (3): 165–168. ISSN   1724-8914. PMC   4269136 . PMID   25568646.
  37. ↑ Pathan, Hasan; Williams, John (2012). "Basic opioid pharmacology: an update". British Journal of Pain. 6 (1): 11–16. doi:10.1177/2049463712438493. ISSN   2049-4637. PMC   4590096 . PMID   26516461.
  38. ↑ Pasternak, Gavril W.; Pan, Ying-Xian (October 2013). "Mu Opioids and Their Receptors: Evolution of a Concept". Pharmacological Reviews. 65 (4): 1257–1317. doi:10.1124/pr.112.007138. ISSN   0031-6997. PMC   3799236 . PMID   24076545.
  39. ↑ "Appendix C – Opioid Pharmacology". ICSI. Archived from the original on 2021-06-08. Retrieved 2019-10-24.
  40. ↑ Webster, Lynn R. (2017). "Risk Factors for Opioid-Use Disorder and Overdose". Anesthesia and Analgesia. 125 (5): 1741–1748. doi: 10.1213/ANE.0000000000002496 . ISSN   1526-7598. PMID   29049118.
  41. ↑ Currow, David C; Phillips, Jane; Clark, Katherine (May 2016). "Using opioids in general practice for chronic non-cancer pain: an overview of current evidence". Medical Journal of Australia. 204 (8): 305–309. doi:10.5694/mja16.00066. hdl: 10453/44764 . ISSN   0025-729X. PMID   27125804. S2CID   8718457.
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