Morphine - Wikipedia, The Free Encyclopedia

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6/12/13 Morphine - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Morphine

Morphine

200px

Systematic (IUPAC) name

(5,6)-7,8-didehydro-

4,5-epoxy-17-methylmorphinan-3,6-diol

Clinical data

Trade names Mscontin, Oramorph

AHFS/Drugs.com monograph

Pregnancy cat. C (AU) C (US)

Legal status Controlled (S8) (AU)

Schedule I (CA) Schedule II

(US) Narcotic Schedules I

and III (UN) Prescription

Medicine OnlyDependence liability Very High (morphine,

among other opiates are

known to cause serious

abuse, tolerance,

dependence and withdrawa

problems)

Routes Inhalation (smoking),

insufflation (snorting), oral,

rectal, subcutaneous (S.C),

intramuscular (I.M),

intravenous (I.V), and

intrathecal (I.T)

Pharmacokinetic data

Bioavailability 20-40% (oral), 36-71%

(rectally),[1] 100% (IV/IM)

Protein binding 3040%

Metabolism Hepatic 90%

MorphineFrom Wikipedia, the free encyclopedia

Morphine (INN) (/mrfin/; MS Contin, MSIR, Avinza,

Kadian, Oramorph, Roxanol, Kapanol) is a potent opiate analgesic

drug that is used to relieve severe pain. It was first isolated in 1804 by

Friedrich Sertrner, first distributed by him in 1817, and first

commercially sold by Merck in 1827, which at the time was a singlesmall chemists' shop. It was more widely used after the invention of the

hypodermic needle in 1857. It tookits name from the Greek god of

dreams Morpheus (Greek:).[2]

After it was isolated from opium by Sertrner, the traditional way to

obtain morphine had been by chemical processing of opium. In India,

opium harvested by licensed poppy farmers is dehydrated to uniform

levels of hydration at government processing centers, and then sold to

pharmaceutical companies, which extract morphine from the opium.

However in Turkey and Tasmania morphine is obtained by harvesting

and processing the fully mature dry seed pods, with attached stalks,calledpoppy straw. By not harvesting opium at all, and by obtaining

morphine only from the dry poppy straw, and not from opium, and by

using a large scale industrial process to do so, at factories located near

the poppy farms, opportunities for illicitly diverting opium from the

crop, and for illicit production of morphine, and heroin from the opium,

are reduced. In Turkey, a water extraction process is used. In

Tasmania, a solvent extraction process is used.

Morphine is the most abundant opiate found in opium, the dried latex

extracted by shallowly slicing the unripe seedpods of thePapaver

somniferum poppy. Morphine was the first active principle purifiedfrom a plant source and is one of at least 50 alkaloids of several

different types present in opium, poppy straw concentrate, and other

poppy derivatives. Morphine is generally 8 to 14 percent of the dry

weight of opium,[3] although specially bred cultivars reach 26 percent

or produce little morphine at all (under 1 percent, perhaps down to

0.04 percent). The latter varieties, including the 'Przemko' and

'Norman' cultivars of the opium poppy, are used to produce two other

alkaloids, thebaine and oripavine, which are used in the manufacture of

semi-synthetic and synthetic opioids like oxycodone and etorphine and

some other types of drugs.P. bracteatum does not contain morphine

or codeine, or other narcotic phenanthrene-type, alkaloids. Thisspecies is rather a source of thebaine.[4] Occurrence of morphine in

other Papaverales and Papaveraceae, as well as in some species of

hops and mulberry trees has not been confirmed. Morphine is

produced most predominantly early in the life cycle of the plant. Past

the optimum point for extraction, various processes in the plant

produce codeine, thebaine, and in some cases negligible amounts of

hydromorphone, dihydromorphine, dihydrocodeine, tetrahydro-

thebaine, and hydrocodone (these compounds are rather synthesized

from thebaine and oripavine). The human body produces

endorphins,[5] which are endogenous opioid peptides that function as
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en.wikipedia.org/wiki/Morphine 2

Half-life 23 hours

Excretion Renal 90%, biliary 10%

Identifiers

CAS number 57-27-2

64-31-3 (neutral sulfate),

52-26-6 (hydrochloride)

ATC code N02AA01

PubChem CID 5288826

IUPHAR ligand 1627

DrugBank DB00295

ChemSpider 4450907

UNII 76I7G6D29C

KEGG D08233

ChEBI CHEBI:17303

ChEMBL CHEMBL70

Chemical data

Formula C17H19NO3

Mol. mass 285.34

Physical data

Solubility in water HCl & sulf.: 60 mg/mL

(20 C)

(what is this?) (verify)

neurotransmitters and have similar effects.[6]

In clinical medicine, morphine is regarded as the gold standard, or

benchmark, of opioid analgesics used to relieve severe or agonizing

pain and suffering. Like other opioids, such as oxycodone,

hydromorphone, and diacetylmorphine (heroin), morphine acts directly

on the central nervous system (CNS) to relieve pain.

Morphine has a high potential for addiction; tolerance andpsychological dependence develop rapidly, although physiological

dependence may take several months to develop. Tolerance to

respiratory depression and euphoria develops more rapidly than

tolerance to analgesia, and many chronic pain patients are being

maintained on a stable dose, for many years.

Contents

1 Medical uses

2 Adverse effects

2.1 Constipation

2.2 Addiction

2.3 Tolerance

2.4 Withdrawal

2.5 Overdose

3 Contraindications

4 Synthesis

5 Pharmacology

5.1 Gene expression

5.2 Effects on the immune system6 Pharmacokinetics

6.1 Absorption and metabolism

6.2 Detection in biological fluids

7 Effects on human performance

8 Chemistry

8.1 Production

8.2 Extraction and detection

9 Biosynthesis

10 History

11 Society and culture11.1 Illicit use

11.2 Slang terms

11.3 Trade names

12 Precursor to other opioids

12.1 Pharmaceutical

12.2 Illicit

13 Legal classification

14 Access in developing countries

15 See also

SMILES

InChI
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A localized reaction to intravenous

morphine caused by histamine release

in the veins.

16 References

17 External links

Medical uses

Morphine is primarily used to treat both acute and chronic severe pain. It is also used for pain due to myocardial infarction

and for labor pains.[7]

There are however concerns that morphine may increase mortality in the setting of non ST elevationmyocardial infarction.[8] Morphine has also traditionally been used in the treatment of the acute pulmonary edema.[7] A 200

review however found little evidence to support this practice.[9]

Immediate release morphine is beneficial in reducing the symptom of acute shortness of breath due to both cancer and non-

cancer causes.[10][11] In the setting of breathlessness at rest or on minimal exertion from conditions such as advanced cance

or end-stage cardio-respiratory diseases, regular, low-dose sustained release morphine significantly reduces breathlessness

safely, with its benefits maintained over time.[12][13]

Its duration of analgesia is about 34 hours when administered via the intravenous, subcutaneous, or intramuscular route and

36 hours when given by mouth.[14] Morphine is also used in slow release formulations for opiate substitution therapy (OST

in Austria, Bulgaria, and Slovenia, for addicts who cannot tolerate the side effects of using either methadone orbuprenorphine, or for addicts who are "not held" by buprenorphine or methadone. It is used for OST in many parts of

Europe although on a limited basis.[15]

Adverse effects

Constipation

Like loperamide and other opioids, morphine acts on the myenteric plexus in the

intestinal tract, reducing gut motility, causing constipation. The gastrointestinal

effects of morphine are mediated primarily by -opioid receptors in the bowel. Byinhibiting gastric emptying and reducing propulsive peristalsis of the intestine,

morphine decreases the rate of intestinal transit. Reduction in gut secretion and

increased intestinal fluid absorption also contribute to the constipating effect.

Opioids also may act on the gut indirectly through tonic gut spasms after inhibition

of nitric oxide generation.[16] This effect was shown in animals when a nitric oxide

precursor, L-Arginine, reversed morphine-induced changes in gut motility.[17]

Addiction

Morphine is a potentially highly addictive substance. It can cause psychological dependence and physical dependence as was tolerance. In the presence of pain and the other disorders for which morphine is indicated, a combination of psychologica

and physiological factors tend to prevent true addiction from developing, although physical dependence and tolerance will

develop with protracted opioid therapy.

In controlled studies comparing the physiological and subjective effects of heroin and morphine in individuals formerly

addicted to opiates, subjects showed no preference for one drug over the other. Equipotent, injected doses had comparabl

action courses, with no difference in subjects' self-rated feelings of euphoria, ambition, nervousness, relaxation, drowsiness,

or sleepiness.[18] Short-term addiction studies by the same researchers demonstrated that tolerance developed at a similar

rate to both heroin and morphine. When compared to the opioids hydromorphone, fentanyl, oxycodone, and

pethidine/meperidine, former addicts showed a strong preference for heroin and morphine, suggesting that heroin and
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morphine are particularly susceptible to abuse and addiction. Morphine and heroin were also much more likely to produce

euphoria and other positive subjective effects when compared to these other opioids.[18] The choice of heroin and morphin

over other opioids by former-drug addicts may also be the result of the fact that heroin (also known as morphine diacetate

diamorphine ordi-acetyl-morphine) is an ester of morphine and a morphine prodrug, essentially meaning that they are

identical drugs in vivo. Heroin is converted to morphine before binding to the opioid receptors in the brain and spinal cord,

where morphine then causes the subjective effects, which is what the addicted individuals are ultimately looking for. [19]

Other studies, such as the Rat Park experiments, suggest that morphine is less physically addictive than others suggest, and

most studies on morphine addiction merely show that "severely distressed animals, like severely distressed people, will relievtheir distress pharmacologically if they can."[20] In these studies, rats with a morphine "addiction" overcome their addiction

themselves when placed in decent living environments with enough space, good food, companionship, areas for exercise, an

areas for privacy. More recent research has shown that an enriched environment may decrease morphine addiction in

mice.[21]

Tolerance

Tolerance to the analgesic effects of morphine is fairly rapid[citation needed]. There are several hypotheses about how

tolerance develops, including opioid receptor phosphorylation (which would change the receptor conformation), functional

decoupling of receptors from G-proteins (leading to receptor desensitization),[22] -opioid receptor internalization and/or

receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the cAM

pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt.[23]) CCK

might mediate some counter-regulatory pathways responsible for opioid tolerance. CCK-antagonist drugs, specifically

proglumide, have been shown to slow the development of tolerance to morphine.

Withdrawal

See also: Opioid withdrawal

Cessation of dosing with morphine creates the prototypical opioid withdrawal syndrome, which, unlike that of barbiturates,

benzodiazepines, alcohol, or sedative-hypnotics, is not fatal by itself in neurologically healthy patients without heart or lungproblems.

Acute morphine along with and other opioid withdrawal proceeds through a number of stages. Other opioids differ in the

intensity and length of each, and weak opioids and mixed agonist-antagonists may have acute withdrawal syndromes that do

not reach the highest level. As commonly cited, they are:

Stage I: Six to fourteen hours after last dose: Drug craving, anxiety, irritability, perspiration, and mild to moderate

dysphoria.

Stage II: Fourteen to eighteen hours after last dose: Yawning, heavy perspiration, mild depression lacrimation, crying

running nose, dysphoria, also intensification of the above symptoms. "yen sleep" (a waking trance-like state)

Stage III: Sixteen to twenty-four hours after last dose: Rhinorrhea (runny nose) and increase in other of the above,dilated pupils, piloerection (goose bumps), muscle twitches, hot flashes, cold flashes, aching bones and muscles, loss

of appetite and the beginning of intestinal cramping.

Stage IV: Twenty-four to thirty-six hours after last dose: Increase in all of the above including severe cramping and

involuntary leg movements ("kicking the habit"), loose stool, insomnia, elevation of blood pressure, moderate elevatio

in body temperature, increase in frequency of breathing and tidal volume, tachycardia (elevated pulse), restlessness,

nausea

Stage V: Thirty-six to seventy-two hours after last dose: Increase in the above, fetal position, vomiting, free and

frequent liquid diarrhea, which sometimes can accelerate the time of passage of food from mouth to out of system to

an hour or less, weight loss of two to five kilos per 24 hours, increased white cell count and other blood changes.
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Stage VI: After completion of above: Recovery of appetite ("the chucks"), and normal bowel function, beginning of

transition to post-acute and chronic symptoms that are mainly psychological but that may also include increased

sensitivity to pain, hypertension, colitis or other gastrointestinal afflictions related to motility, and problems with weigh

control in either direction.

The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next

scheduled dose, sometimes within as early as a few hours (usually between 612 hours) after the last administration. Early

symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria, sweating and in some cases a strong

drug craving. Severe headache, restlessness, irritability, loss of appetite, body aches, severe abdominal pain, nausea andvomiting, tremors, and even stronger and more intense drug craving appear as the ome progresses. Severe depression and

vomiting are very common. During the acute withdrawal period systolic and diastolic blood pressure increase, usually beyon

pre-morphine levels, and heart rate increases,[24] which have potential to cause a heart attack, blood clot, or stroke.

Chills or cold flashes with goose bumps ("cold turkey") alternating with flushing (hot flashes), kicking movements of the legs

("kicking the habit"[25]) and excessive sweating are also characteristic symptoms.[26] Severe pains in the bones and muscles

of the back and extremities occur, as do muscle spasms. At any point during this process, a suitable narcotic can be

administered that will dramatically reverse the withdrawal symptoms. Major withdrawal symptoms peak between 48 and 96

hours after the last dose and subside after about 8 to 12 days. Sudden withdrawal by heavily dependent users who are in

poor health is very rarely fatal. Morphine withdrawal is considered less dangerous than alcohol, barbiturate, or

benzodiazepine withdrawal.[27][28]

The psychological dependence associated with morphine addiction is complex and protracted. Long after the physical need

for morphine has passed, the addict will usually continue to think and talk about the use of morphine (or other drugs) and fe

strange or overwhelmed coping with daily activities without being under the influence of morphine. Psychological withdrawa

from morphine is a very long and painful process.[29] Addicts often suffer severe depression, anxiety, insomnia, mood swing

amnesia (forgetfulness), low self-esteem, confusion, paranoia, and other psychological disorders. Without intervention, the

syndrome will run its course, and most of the overt physical symptoms will disappear within 7 to 10 days including

psychological dependence. There is a high probability that relapse will occur after morphine withdrawal when neither the

physical environment nor the behavioral motivators that contributed to the abuse have been altered. Testimony to morphine

addictive and reinforcing nature is its relapse rate. Abusers of morphine (and heroin) have one of the highest relapse rates

among all drug users, ranging up to 98 per cent in the estimation of some clinicians, neuropharmacologists, mentalhealth/AODA professionals and other medical experts.[30]

Overdose

A large overdose can cause asphyxia and death by respiratory depression if the person does not receive medical attention

immediately.[31] Overdose treatment includes the administration of naloxone. The latter completely reverses morphine's

effects, but precipitates immediate onset of withdrawal in opiate-addicted subjects. Multiple doses may be needed. [31]

The minimum lethal dose is 200 mg but in case of hypersensitivity 60 mg can bring sudden death. In case of drug addiction,

23 g/day can be tolerated.[32]

Contraindications

The following conditions are relative contraindications for morphine:

acute respiratory depression

renal failure (due to accumulation of the metabolites morphine-3-glucuronide and morphine-6-glucuronide)

chemical toxicity (potentially lethal in low tolerance subjects)

raised intracranial pressure, including head injury (risk of worsening respiratory depression)
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Biliary colic.[33]

Although it has previously been thought that morphine was contraindicated in acute pancreatitis, a review of the literature

shows no evidence for this.[34]

Synthesis

The first synthesis by Marshall D. Gates, Jr. in 1952 is considered a classic in the field. [35][36] Several other syntheses were

reported, notably by the research groups of Rice,[37] Evans,[38] Fuchs,[39] Parker,[40] Overman,[41] Mulzer-Trauner,[42]

White,[43] Taber,[44] Trost,[45] Fukuyama,[46] Guillou[47] and Stork.[48]

Pharmacology

Main article: Opioid receptor

Endogenous opioids include endorphins, enkephalins, dynorphins, and even morphine itself. Morphine appears to mimic

endorphins. Endorphins, a contraction of the term endogenous morphines, are responsible for analgesia (reducing pain),

causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or

excitement.

Morphine is the prototype narcotic drug and is the standard against which all other opioids are tested. It interacts

predominantly with the -opioid receptor. These -binding sites are discretely distributed in the human brain, with high

densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They ar

also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in

the spinal nucleus of the trigeminal nerve.[49]

Morphine is a phenanthrene opioid receptor agonist its main effect is binding to and activating the -opioid receptors in th

central nervous system. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system

and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Activation of the -opioid

receptors is associated with analgesia, sedation, euphoria, physical dependence, and respiratory depression. Morphine is arapid-acting narcotic, and it is known to bind very strongly to the -opioid receptors, and for this reason, it often has a high

incidence of euphoria/dysphoria, respiratory depression, sedation, pruritus, tolerance, and physical and psychological

dependence when compared to other opioids at equianalgesic doses. Morphine is also a -opioid and -opioid receptor

agonist, -opioid's action is associated with spinal analgesia, miosis (pinpoint pupils) and psychotomimetic effects. -opioid

thought to play a role in analgesia.[49] Although morphine does not bind to the -receptor, it has been shown that -agonist

such as (+)-pentazocine, antagonize morphine analgesia, and -antagonists enhance morphine analgesia,[50] suggesting som

interaction between morphine and the -opioid receptor.

The effects of morphine can be countered with opioid antagonists such as naloxone and naltrexone; the development of

tolerance to morphine may be inhibited by NMDA antagonists such as ketamine or dextromethorphan.[51] The rotation of

morphine with chemically dissimilar opioids in the long-term treatment of pain will slow down the growth of tolerance in the

longer run, particularly agents known to have significantly incomplete cross-tolerance with morphine such as levorphanol,

ketobemidone, piritramide, and methadone and its derivatives; all of these drugs also have NMDA antagonist properties. It

believed that the strong opioid with the most incomplete cross-tolerance with morphine is either methadone or

dextromoramide.

Gene expression
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Studies have shown that morphine can alter the expression of a number of genes. A single injection of morphine has been

shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for

cytoskeleton-related proteins.[52]

Effects on the immune system

Morphine has long been known to act on receptors expressed on cells of the central nervous system resulting in pain relief

and analgesia. In the 1970s and '80s, evidence suggesting that opiate drug addicts show increased risk of infection (such as

increased pneumonia, tuberculosis, and HIV) led scientists to believe that morphine may also affect the immune system. Thipossibility increased interest in the effect of chronic morphine use on the immune system.

The first step of determining that morphine may affect the immune system was to establish that the opiate receptors known t

be expressed on cells of the central nervous system are also expressed on cells of the immune system. One study successfu

showed that dendritic cells, part of the innate immune system, display opiate receptors. Dendritic cells are responsible for

producing cytokines, which are the tools for communication in the immune system. This same study showed that dendritic

cells chronically treated with morphine during their differentiation produce more interleukin-12 (IL-12), a cytokine

responsible for promoting the proliferation, growth, and differentiation of T-cells (another cell of the adaptive immune system

and less interleukin-10 (IL-10), a cytokine responsible for promoting a B-cell immune response (B cells produce antibodies

to fight off infection).[53]

This regulation of cytokines appear to occur via the p38 MAPKs (mitogen-activated protein kinase)-dependent pathway.

Usually, the p38 within the dendritic cell expresses TLR 4 (toll-like receptor 4), which is activated through the ligand LPS

(lipopolysaccharide). This causes the p38 MAPK to be phosphorylated. This phosphorylation activates the p38 MAPK to

begin producing IL-10 and IL-12. When the dendritic cells are chronically exposed to morphine during their differentiation

process then treated with LPS, the production of cytokines is different. Once treated with morphine, the p38 MAPK does

not produce IL-10, instead favoring production of IL-12. The exact mechanism through which the production of one

cytokine is increased in favor over another is not known. Most likely, the morphine causes increased phosphorylation of the

p38 MAPK. Transcriptional level interactions between IL-10 and IL-12 may further increase the production of IL-12 once

IL-10 is not being produced. This increased production of IL-12 causes increased T-cell immune response.

Further studies on the effects of morphine on the immune system have shown that morphine influences the production ofneutrophils and other cytokines. Since cytokines are produced as part of the immediate immunological response

(inflammation), it has been suggested that they may also influence pain. In this way, cytokines may be a logical target for

analgesic development. Recently, one study has used an animal model (hind-paw incision) to observe the effects of morphin

administration on the acute immunological response. Following hind-paw incision, pain thresholds and cytokine production

were measured. Normally, cytokine production in and around the wounded area increases in order to fight infection and

control healing (and, possibly, to control pain), but pre-incisional morphine administration (0.1-10.0 mg/kg) reduced the

number of cytokines found around the wound in a dose-dependent manner. The authors suggest that morphine administratio

in the acute post-injury period may reduce resistance to infection and may impair the healing of the wound. [54]

PharmacokineticsAbsorption and metabolism

Morphine can be taken orally, sublingually, bucally, rectally, subcutaneously, intravenously, intrathecally or epidurally and

inhaled via a nebulizer. On the streets, it is becoming more common to inhale (Chasing the Dragon"), but, for medical

purposes, intravenous (IV) injection is the most common method of administration. Morphine is subject to extensive first-

pass metabolism (a large proportion is broken down in the liver), so, if taken orally, only 4050% of the dose reaches the

central nervous system. Resultant plasma levels after subcutaneous (SC), intramuscular (IM), and IV injection are all

comparable. After IM or SC injections, morphine plasma levels peak in approximately 20 minutes, and, after oral

administration, levels peak in approximately 30 minutes.[55] Morphine is metabolised primarily in the liver and approximatel
http://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Metabolisedhttp://en.wikipedia.org/wiki/Morphine#cite_note-55http://en.wikipedia.org/wiki/First-pass_metabolismhttp://en.wikipedia.org/wiki/Chasing_the_Dragonhttp://en.wikipedia.org/wiki/Epiduralhttp://en.wikipedia.org/wiki/Intrathecalhttp://en.wikipedia.org/wiki/Intravenoushttp://en.wikipedia.org/wiki/Subcutaneous_injectionhttp://en.wikipedia.org/wiki/Buccal_spacehttp://en.wikipedia.org/wiki/Sublingual_administrationhttp://en.wikipedia.org/wiki/Morphine#cite_note-54http://en.wikipedia.org/wiki/Infectionhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Neutrophilshttp://en.wikipedia.org/wiki/P38_mitogen-activated_protein_kinaseshttp://en.wikipedia.org/wiki/Phosphorylationhttp://en.wikipedia.org/wiki/Lipopolysaccharidehttp://en.wikipedia.org/wiki/TLR_4http://en.wikipedia.org/wiki/P38_MAPK_pathwayhttp://en.wikipedia.org/wiki/Morphine#cite_note-messmer_2006-53http://en.wikipedia.org/wiki/Interleukin-10http://en.wikipedia.org/wiki/Interleukin-12http://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Human_immunodeficiency_virushttp://en.wikipedia.org/wiki/Tuberculosishttp://en.wikipedia.org/wiki/Pneumoniahttp://en.wikipedia.org/wiki/Analgesiahttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Morphine#cite_note-52http://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Mitochondrialhttp://en.wikipedia.org/wiki/Genes


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87% of a dose of morphine is excreted in the urine within 72 hours of administration. Morphine is metabolized primarily into

morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)[56] via glucuronidation by phase II metabolism enzym

UDP-glucuronosyl transferase-2B7 (UGT2B7). About 60% of morphine is converted to M3G, and 610% is converted to

M6G.[57] Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys. M3G doe

not undergo opioid receptor binding and has no analgesic effect. M6G binds to -receptors and is half as potent an analges

as morphine in humans.[57] Morphine may also be metabolized into small amounts of normorphine, codeine, and

hydromorphone. Metabolism rate is determined by gender, age, diet, genetic makeup, disease state (if any), and use of othe

medications. The elimination half-life of morphine is approximately 120 minutes, though there may be slight differences

between men and women. Morphine can be stored in fat, and, thus, can be detectable even after death. Morphine is able tocross the bloodbrain barrier, but, because of poor lipid solubility, protein binding, rapid conjugation with glucuronic acid

and ionization, it does not cross easily. Diacetylmorphine, which is derived from morphine, crosses the bloodbrain barrier

more easily, making it more potent.[58]

Detection in biological fluids

Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, may be quantitated in blood,

plasma, or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Most

commercial opiate screening tests based on immunoassays cross-react appreciably with these metabolites. However,

chromatographic techniques can easily distinguish and measure each of these substances. When interpreting the results of a

test, it is important to consider the morphine usage history of the individual, since a chronic user can develop tolerance to

doses that would incapacitate an opiate-naive individual, and the chronic user often has high baseline values of these

metabolites in his system. Furthermore, some testing procedures employ a hydrolysis step prior to quantitation that converts

the metabolic products to morphine, yielding a result that may be many times larger than with a method that examines each

product individually. Interpretation can be confounded by usage of codeine or ingestion of poppy seed foods, either of whic

leads to the presence of morphine and its conjugated metabolites in a person's biofluids. [59]

Effects on human performance

Most reviews conclude that opioids produce minimal impairment of human performance on tests of sensory, motor, or

attentional abilities. However, recent studies have been able to show some impairments caused by morphine, which is notsurprising, given that morphine is a central nervous system depressant. Morphine has resulted in impaired functioning on

critical flicker frequency (a measure of overall CNS arousal) and impaired performance on the Maddox Wing test (a

measure of deviation of the visual axes of the eyes). Few studies have investigated the effects of morphine on motor abilities

a high dose of morphine can impair finger tapping and the ability to maintain a low constant level of isometric force (i.e. fine

motor control is impaired),[60] though no studies have shown a correlation between morphine and gross motor abilities.

In terms of cognitive abilities, one study has shown that morphine may have a negative impact on anterograde and retrograd

memory,[61] but these effects are minimal and are transient. Overall, it seems that acute doses of opioids in non-tolerant

subjects produce minor effects in some sensory and motor abilities, and perhaps also in attention and cognition. It is likely

that the effects of morphine will be more pronounced in opioid-naive subjects than chronic opioid users.

In chronic opioid users, such as those on Chronic Opioid Analgesic Therapy (COAT) for managing severe, chronic pain,

behavioural testing has shown normal functioning on perception, cognition, coordination and behaviour in most cases. One

recent study[62] analysed COAT patients in order to determine whether they were able to safely operate a motor vehicle.

The findings from this study suggest that stable opioid use does not significantly impair abilities inherent in driving (this includ

physical, cognitive and perceptual skills). COAT patients showed rapid completion of tasks that require speed of respondin

for successful performance (e.g., Rey Complex Figure Test) but made more errors than controls. COAT patients showed n

deficits in visual-spatial perception and organization (as shown in the WAIS-R Block Design Test) but did show impaired

immediate and short-term visual memory (as shown on the Rey Complex Figure Test Recall). These patients showed no

impairments in higher order cognitive abilities (i.e., Planning). COAT patients appeared to have difficulty following
http://en.wikipedia.org/wiki/Wechsler_Adult_Intelligence_Scalehttp://en.wikipedia.org/wiki/Rey_Complex_Figurehttp://en.wikipedia.org/wiki/Morphine#cite_note-62http://en.wikipedia.org/wiki/Chronic_painhttp://en.wikipedia.org/wiki/Attentionhttp://en.wikipedia.org/wiki/Morphine#cite_note-61http://en.wikipedia.org/wiki/Retrograde_amnesiahttp://en.wikipedia.org/wiki/Anterograde_amnesiahttp://en.wikipedia.org/wiki/Cognitivehttp://en.wikipedia.org/wiki/Morphine#cite_note-60http://en.wikipedia.org/wiki/Isometric_exercisehttp://en.wikipedia.org/wiki/Depressanthttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Morphine#cite_note-59http://en.wikipedia.org/wiki/Morphine#cite_note-Jenkins_AJ_2008-58http://en.wikipedia.org/wiki/Diacetylmorphinehttp://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttp://en.wikipedia.org/wiki/Half-lifehttp://en.wikipedia.org/wiki/Hydromorphonehttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Normorphinehttp://en.wikipedia.org/wiki/Morphine#cite_note-van_Dorp-57http://en.wikipedia.org/wiki/Morphine#cite_note-van_Dorp-57http://en.wikipedia.org/wiki/UGT2B7http://en.wikipedia.org/wiki/Glucuronidationhttp://en.wikipedia.org/wiki/Morphine#cite_note-56http://en.wikipedia.org/wiki/Morphine-6-glucuronidehttp://en.wikipedia.org/wiki/Morphine-3-glucuronidehttp://en.wikipedia.org/wiki/Urine


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Chemical structure of

morphine. The

benzylisoquinoline backbone i

shown in green.

Same structure with correct

3D configuration; backbone in

blue.

instructions and showed a propensity toward impulsive behaviour, yet this did not reach statistical significance. It is importan

to note that this study reveals that COAT patients have no domain-specific deficits, which supports the notion that chronic

opioid use has minor effects on psychomotor, cognitive, or neuropsychological functioning.

It is difficult to study the performance effects of morphine without considering why a person is taking morphine. Opioid-naiv

subjects are volunteers in a pain-free state. However, most chronic-users of morphine use it to manage pain. Pain is a

stressor and so it can confound performance results, especially on tests that require a large degree of concentration. Pain is

also variable, and will vary over time and from person to person. It is unclear to what extent the stress of pain may cause

impairments, and it is also unclear whether morphine is potentiating or attenuating these impairments.

Chemistry

Morphine is a benzylisoquinoline alkaloid with two additional ring closures. It has:

A rigid pentacyclic structure consisting of a benzene ring (A), two partially

unsaturatedcyclohexane rings (B and C), a piperidine ring (D) and a

tetrahydrofuran ring (E). Rings A, B and C are the phenanthrene ring system. This

ring system has little conformational flexibility.

Two hydroxyl functional groups: a A3-phenolic OH (pKa 9.9) and a C6-allylic

OH

An ether linkage between C4 and C5,

Unsaturation between C7 and C8,

A basic, 3o-amine function at position 17,

5 centers of chirality (C5, C6, C9, C13 and C14) with morphine exhibiting a high

degree of stereoselectivity of analgesic action.[63]

Most of the licit morphine produced is used to make codeine by methylation. It is also a

precursor for many drugs including heroin (3,6-diacetylmorphine), hydromorphone

(dihydromorphinone), and oxymorphone (14-hydroxydihydromorphinone); many

morphine derivatives are can also be manufactured using thebaine and/or codeine as astarting material. Replacement of the N-methyl group of morphine with an N-phenylethyl

group results in a product that is 18 times more powerful than morphine in its opiate

agonist potency. Combining this modification with the replacement of the 6-hydroxyl with

a 6-methylene group produces a compound some 1,443 times more potent than

morphine, stronger than the Bentley compounds such as etorphine (M99, the

Immobilon tranquilliser dart) by some measures.

The structure-activity relationship of morphine has been extensively studied. As a result of

the extensive study and use of this molecule, more than 250 morphine derivatives (also

counting codeine and related drugs) have been developed since the last quarter of the 19th century. These drugs range from

25 percent the analgesic strength of codeine (or slightly more than 2 percent of the strength of morphine) to several thousandtimes the strength of morphine, to powerful opioid antagonists, including naloxone (Narcan), naltrexone (Trexan),

diprenorphine (M5050, the reversing agent for the Immobilon dart) and nalorphine (Nalline). Some opioid agonist-

antagonists, partial agonists, and inverse agonists are also derived from morphine. The receptor-activation profile of the sem

synthetic morphine derivatives varies widely and some, like apomorphine are devoid of narcotic effects.

Morphine and most of its derivatives do not exhibit optical isomerism, although some more distant relatives like the

morphinan series (levorphanol, dextorphan and the racemic parent chemical dromoran) do, and as noted above

stereoselectivity in vivo is an important issue.
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Morphine-derived agonistantagonist drugs have also been developed. Elements of the morphine structure have been used

create completely synthetic drugs such as the morphinan family (levorphanol, dextromethorphan and others) and other grou

that have many members with morphine-like qualities. The modification of morphine and the aforementioned synthetics has

also given rise to non-narcotic drugs with other uses such as emetics, stimulants, antitussives, anticholinergics, muscle

relaxants, local anaesthetics, general anaesthetics, and others.

Most semi-synthetic opioids, both of the morphine and codeine subgroups, are created by modifying one or more of the

following:

Halogenating or making other modifications at positions 1 and/or 2 on the morphine carbon skeleton.

The methyl group that makes morphine into codeine can be removed or added back, or replaced with another

functional group like ethyl and others to make codeine analogues of morphine-derived drugs and vice versa. Codeine

analogues of morphine-based drugs often serve as prodrugs of the stronger drug, as in codeine and morphine,

hydrocodone and hydromorphone, oxycodone and oxymorphone, nicocodeine and nicomorphine, dihydrocodeine

and dihydromorphine, etc.

Saturating, opening, or other changes to the bond between positions 7 and 8, as well as adding, removing, or

modifying functional groups to these positions; saturating, reducing, eliminating, or otherwise modifying the 7-8 bond

and attaching a functional group at 14 yields hydromorphinol; the oxidation of the hydroxyl group to a carbonyl and

changing the 7-8 bond to single from double changes codeine into oxycodone.

Attachment, removal or modification of functional groups to positions 3 and/or 6 (dihydrocodeine and related,hydrocodone, nicomorphine); in the case of moving the methyl functional group from position 3 to 6, codeine becom

heterocodeine, which is 72 times stronger, and therefore six times stronger than morphine

Attachment of functional groups or other modification at position 14 (oxymorphone, oxycodone, naloxone)

Modifications at positions 2, 4, 5 or 17, usually along with other changes to the molecule elsewhere on the morphine

skeleton. Often this is done with drugs produced by catalytic reduction, hydrogenation, oxidation, or the like,

producing strong derivatives of morphine and codeine.

Both morphine and its hydrated form, C17H19NO3H2O, are sparingly soluble in water. In five liters of water, only one gram

of the hydrate will dissolve. For this reason, pharmaceutical companies produce sulfate and hydrochloride salts of the drug,

both of which are over 300 times more water-soluble than their parent molecule. Whereas the pH of a saturated morphine

hydrate solution is 8.5, the salts are acidic. Since they derive from a strong acid but weak base, they are both at about pH =

5; as a consequence, the morphine salts are mixed with small amounts of NaOH to make them suitable for injection. [64]

A number of salts of morphine are used, with the most common in current clinical use being the hydrochloride, sulfate,

tartrate, and citrate; less commonly methobromide, hydrobromide, hydroiodide, lactate, chloride, and bitartrate and the

others listed below. Morphine diacetate, which is another name for heroin, is a Schedule I controlled substance, so it is not

used clinically in the United States; it is a sanctioned medication in the United Kingdom and in Canada and some countries i

Continental Europe, its use being particularly common (nearly to the degree of the hydrochloride salt) in the United Kingdom

Morphine meconate is a major form of the alkaloid in the poppy, as is morphine pectinate, nitrate, sulphate, and some other

Like codeine, dihydrocodeine and other, especially older, opiates, morphine has been used as the salicylate salt by some

suppliers and can be easily compounded, imparting the therapeutic advantage of both the opioid and the NSAID; multiplebarbiturate salts of morphine were also used in the past, as was/is morphine valerate, the salt of the acid being the active

principle of valerian. Calcium morphenate is the intermediate in various latex and poppy-straw methods of morphine

production, more rarely sodium morphenate takes its place. Morphine ascorbate and other salts such as the tannate, citrate

and acetate, phosphate, valerate and others may be present in poppy tea depending on the method of preparation. Morphin

valerate produced industrially was one ingredient of a medication available for both oral and parenteral administration popul

many years ago in Europe and elsewhere called Trivalin (not to be confused with the current, unrelated herbal preparation o

the same name), which also included the valerates of caffeine and cocaine, with a version containing codeine valerate as a

fourth ingredient being distributed under the name Tetravalin.
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Closely related to morphine are the opioids morphine-N-oxide (genomorphine), which is a pharmaceutical that is no longer

common use; and pseudomorphine, an alkaloid that exists in opium, form as degradation products of morphine.

The salts listed by the United States Drug Enforcement Administration for reporting purposes, in addition to a few others, a

as follows:

Select forms of morphine as 'morphiniums' or N-protonated cations of morphine, i.e. ionic salts & chemical form

with freebase conversion ratios: Click to
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Salt or drug CSA schedule ACSCN Free base conversion ratio

Morphine (base) II 9300 1

Morphine citrate II 9300 0.81

Morphine bitartrate II 9300 0.66

Morphine stearate II 9300 0.51

Morphine phthalate II 9300 0.89

Morphine hydrobromide II 9300 0.78

Morphine hydrobromide (2 H2O) II 9300 0.71

Morphine hydrochloride II 9300 0.89

Morphine hydrochloride (3 H2O) II 9300 0.76

Morphine acetate II 9300 0.71

Morphine hydriodide (2 H2O) II 9300 0.64

Morphine lactate II 9300 0.76

Morphine monohydrate II 9300 0.94Morphine meconate (5 H2O) II 9300 0.66

Morphine mucate II 9300 0.57

Morphine nitrate II 9300 0.82

Morphine phosphate (1/2 H2O) II 9300 0.73

Morphine phosphate (7 H2O) II 9300 0.73

Morphine salicylate II 9300

Morphine phenylpropionate II 9300 0.65Morphine methyliodide II 9300 0.67

Morphine isobutyrate II 9300 0.76

Morphine hypophosphite II 9300 0.81

Morphine sulfate (5 H2O) II 9300 0.75

Morphine tannate II 9300

Morphine tartrate (3 H2O) II 9300 0.74

Morphine valerate II 9300 0.74

Morphine diacetate I 9200 0.74

Morphine methylbromide I 9305 0.75

Morphine methylsulfonate I 9306 0.75

Morphine-N-oxide I 9307 1

Morphine-N-oxide quinate I 9307 0.60

Pseudomorphine I not mentioned
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Production

In the opium poppy the alkaloids are bound to meconic acid. The method is to

extract from the crushed plant with diluted sulfuric acid, which is a stronger acid

than meconic acid, but not so strong to react with alkaloid molecules. The

extraction is performed in many steps (one amount of crushed plant is at least six

to ten times extracted, so practically every alkaloid goes into the solution). From

the solution obtained at the last extraction step, the alkaloids are precipitated by

either ammonium hydroxide or sodium carbonate. The last step is purifying andseparating morphine from other opium alkaloids. The somewhat similar Gregory

process was developed in the United Kingdom during the Second World War,

which begins with stewing the entire plant, in most cases save the roots and leaves,

in plain or mildly acidified water, then proceeding through steps of concentration, extraction, and purification of

alkaloids.[65][66] Other methods of processing poppy straw use steam, one or more of several types of alcohol, or other

organic solvents.

The poppy straw methods predominate in Continental Europe and the British Commonwealth, with the latex method in mos

common use in India. The latex method can involve either vertical or horizontal slicing of the unripe pods with a two-to five-

bladed knife with a guard developed specifically for this purpose to the depth of a fraction of a millimetre and scoring of the

pods can be done up to five times. An alternative latex method sometimes used in China in the past is to cut off the poppyheads, run a large needle through them, and collect the dried latex 24 to 48 hours later. [67]

Opium poppy contains at least 50 different alkaloids, but most of them are of very low concentration. Morphine is the

principal alkaloid in raw opium and constitutes ~8-19% of opium by dry weight (depending on growing conditions).[58]

Some purpose-developed strains of poppy now produce opium that is up to 26 percent morphine by weight.[68] A rough

rule of thumb to determine the morphine content of pulverised dried poppy straw is to divide the percentage expected for th

strain or crop via the latex method by eight or an empirically determined factor, which is often in the range of 5 to 15.[68] Th

Norman strain ofP. Somniferum, also developed in Tasmania, produces down to 0.04 percent morphine but with much

higher amounts of thebaine and oripavine, which can be used to synthesise semi-synthetic opioids as well as other drugs like

stimulants, emetics, opioid antagonists, anticholinergics, and smooth-muscle agents.[68]

In the 1950s and 1960s, Hungary supplied nearly 60% of Europe's total medication-purpose morphine production. To this

day, poppy farming is legal in Hungary, but poppy farms are limited by law to 2 acres (8,100 m2). It is also legal to sell drie

poppy in flower shops for use in floral arrangements.

It was announced in 1973 that a team at the National Institutes of Health in the United States had developed a method for

total synthesis of morphine, codeine, and thebaine using coal tar as a starting material. A shortage in codeine-hydrocodone

class cough suppressants (all of which can be made from morphine in one or more steps, as well as from codeine or

thebaine) was the initial reason for the research.

Most morphine produced for pharmaceutical use around the world is actually converted into codeine as the concentration o

the latter in both raw opium and poppy straw is much lower than that of morphine; in most countries, the usage of codeine(both as end-product and precursor) is at least equal or greater than that of morphine on a weight basis.

Extraction and detection

Morphine can be isolated from whole blood samples by solid phase extraction (SPE) and detected using liquid

chromatography-mass spectrometry (LC-MS).

Biosynthesis
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The morphine is biosynthesized from the tetrahydroisoquinoline reticuline. It is converted into salutaridine, thebaine, and

oripavine. The involucrated enzymes in this process are the salutaridine synthase, salutaridine:NADPH 7-oxidoreductase an

the codeinone reductase[69]

History

An opium-based elixir has been ascribed to alchemists of Byzantine times, but the specific formula was lost during the

Ottoman conquest of Constantinople (Istanbul).[70] Around 1522, Paracelsus made reference to an opium-based elixir that

he called laudanum from the Latin word laudare, meaning "to praise" He described it as a potent painkiller, but

recommended that it be used sparingly. In the late eighteenth century, when the East India Company gained a direct interest

in the opium trade through India, another opiate recipe called laudanum became very popular among physicians and their

patients.

Morphine was discovered as the first active alkaloid extracted from the opium poppy plant in December 1804 in Paderborn

Germany, by Friedrich Sertrner.[71] The drug was first marketed to the general public by Sertrner and Company in 1817

as an analgesic, and also as a treatment for opium and alcohol addiction. Commercial production began in Darmstadt,

Germany in 1827 by the pharmacy that became the pharmaceutical company Merck, with morphine sales being a large par

of their early growth.[67]
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Friedrich Sertrner

Advertisement for curing morphine

addiction, ca. 1900[78]

An ampoule of morphine with integral

needle for immediate use. From

WWII. On display at the Army

Medical Services Museum.

Later it was found that morphine was more addictive than either alcohol or opium, and its

extensive use during the American Civil War allegedly resulted in over 400,000[72] sufferers

from the "soldier's disease" of morphine addiction.[73][74] This idea has been a subject of

controversy, as there have been suggestions that such a disease was in fact a fabrication; the

first documented use of the phrase "soldier's disease" was in 1915.[75][76]

Diacetylmorphine (better known as heroin) was synthesized from morphine in 1874 and

brought to market by Bayer in 1898. Heroin is approximately 1.5 to 2 times more potent than

morphine weight for weight. Due to the lipid solubility of diacetylmorphine, it is able to crossthe bloodbrain barrier faster than morphine, subsequently increasing the reinforcing

component of addiction.[77] Using a variety of subjective and objective measures, one study estimated the relative potency

heroin to morphine administered intravenously to post-addicts to be 1.802.66 mg of morphine sulfate to 1 mg of

diamorphine hydrochloride (heroin).[18]

Morphine became a controlled

substance in the US under the Harrison

Narcotics Tax Act of 1914, and

possession without a prescription in the

US is a criminal offense. Morphine was

the most commonly abused narcoticanalgesic in the world until heroin was

synthesized and came into use. In general, until the synthesis of dihydromorphine

(ca. 1900), the dihydromorphinone class of opioids (1920s), and oxycodone

(1916) and similar drugs, there were no other drugs in the same efficacy range as

opium, morphine, and heroin, with synthetics still several years away (pethidine

was invented in Germany in 1937) and opioid agonists among the semi-synthetics

were analogues and derivatives of codeine such as dihydrocodeine (Paracodin),

ethylmorphine (Dionine), and benzylmorphine (Peronine). Even today, morphine i

the most sought after prescription narcotic by heroin addicts when heroin is scarc

all other things being equal; local conditions and user preference may cause hydromorphone, oxymorphone, high-dose

oxycodone, or methadone as well as dextromoramide in specific instances such as 1970s Australia, to top that particular lisThe stop-gap drugs used by the largest absolute number of heroin addicts is probably codeine, with significant use also of

dihydrocodeine, poppy straw derivatives like poppy pod and poppy seed tea, propoxyphene, and tramadol.

The structural formula of morphine was determined by 1925 by Robert Robinson. At least three methods of total synthesis

morphine from starting materials such as coal tar and petroleum distillates have been patented, the first of which was

announced in 1952, by Dr. Marshall D. Gates, Jr. at the University of Rochester. [79] Still, the vast majority of morphine is

derived from the opium poppy by either the traditional method of gathering latex from the scored, unripe pods of the poppy

or processes using poppy straw, the dried pods and stems of the plant, the most widespread of which was invented in

Hungary in 1925 and announced in 1930 by the chemist Jnos Kbay.

In 2003, there was discovery of endogenous morphine occurring naturally in the human body. Thirty years of speculationwere made on this subject because there was a receptor that, it appeared, reacted only to morphine: the mu3 opiate recepto

in human tissue.[80] Human cells that form in reaction to cancerous neuroblastoma cells have been found to contain trace

amounts of endogenous morphine.[81]

Society and culture

Illicit use
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Example of different morphine

tablets

The euphoria, comprehensive alleviation of distress and therefore all aspects of

suffering, promotion of sociability and empathy, "body high", and anxiolysis provided

by narcotic drugs including the opioids can cause the use of high doses in the absence

of pain for a protracted period, which can impart a morbid craving for the drug in the

user. Being the prototype of the entire opioid class of drugs means that morphine has

properties that may lend it to misuse. Morphine addiction is the model upon which the

current perception of addiction is based.

Animal and human studies and clinical experience back up the contention thatmorphine is one of the most euphoric of drugs on earth, and via all but the IV route

heroin and morphine cannot be distinguished according to studies because heroin is a

prodrug for the delivery of systemic morphine. Chemical changes to the morphine

molecule yield other euphorigenics such as dihydromorphine, hydromorphone

(Dilaudid, Hydal), and oxymorphone (Numorphan, Opana), as well as the latter three's

methylated equivalents dihydrocodeine, hydrocodone, and oxycodone, respectively; in

addition to heroin, there are dipropanoylmorphine, diacetyldihydromorphine, and other

members of the 3,6 morphine diester category like nicomorphine and other similar

semi-synthetic opiates like desomorphine, hydromorphinol, etc. used clinically in many

countries of the world but in many cases also produced illicitly in rare instances.

In general, misuse of morphine entails taking more than prescribed or outside of

medical supervision, injecting oral formulations, mixing it with unapproved potentiators

such as alcohol, cocaine, and the like, and/or defeating the extended-release

mechanism by chewing the tablets or turning into a powder for snorting or preparing

injectables. The latter method can be every bit as time-consuming and involved as

traditional methods of smoking opium. This and the fact that the liver destroys a large

percentage of the drug on the first pass impacts the demand side of the equation for

clandestine re-sellers, as many customers are not needle users and may have been

disappointed with ingesting the drug orally. As morphine is generally as hard or harder

to divert than oxycodone in a lot of cases, morphine in any form is uncommon on the

street, although ampoules and phials of morphine injection, pure pharmaceuticalmorphine powder, and soluble multi-purpose tablets are very popular where available.

Morphine is also available in a paste that is used in the production of heroin, which can be smoked by itself or turned to a

soluble salt and injected; the same goes for the penultimate products of the Kompot (Polish Heroin) and black tar processe

Poppy straw as well as opium can yield morphine of purity levels ranging from poppy tea to near-pharmaceutical-grade

morphine by itself or with all of the more than 50 other alkaloids. It also is the active narcotic ingredient in opium and all of i

forms, derivatives, and analogues as well as forming from breakdown of heroin and otherwise present in many batches of

illicit heroin as the result of incomplete acetylation.

Slang terms

Morphine is known on the street and elsewhere as M, sister morphine, Vitamin M, morpho, etc.

MS Contin tablets are known as misties, and the 100 mg extended-release tablets as greys and blockbusters. The

"speedball" can use morphine as the narcotic component, which is combined with cocaine, amphetamines, methylphenidate,

or similar drugs. "Blue Velvet" is a combination of morphine with the antihistamine tripelennamine (Pyrabenzamine, PBZ,

Pelamine) taken by injection, or less commonly the mixture when swallowed or used as a retention enema; the name is also

known to refer to a combination of tripelennamine and dihydrocodeine or codeine tablets or syrups taken by mouth.

"Morphia" is an older official term for morphine also used as a slang term. "Driving Miss Emma" is intravenous administratio
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of morphine. Multi-purpose tablets (readi

Documents

Morphine - Wikipedia, The Free Encyclopedia