Morphine (INN) (pronounced /ˈmɔrfiːn/) is Morphine (INN) (pronounced /ˈmɔrfiːn/) is a highly potent opiate analgesic drug, is a highly potent opiate analgesic drug, is the principal active agent in opium, and is the principal active agent in opium, and is considered to be the prototypical opioid. considered to be the prototypical opioid. Like other opioids, e.g. oxycodone, Like other opioids, e.g. oxycodone, hydromorphone , and diacetylmorphine hydromorphone , and diacetylmorphine (heroin), morphine acts directly on the (heroin), morphine acts directly on the central nervous system (CNS) to relieve central nervous system (CNS) to relieve pain. Morphine has a high potential for pain. Morphine has a high potential for addiction; tolerance and both physical and addiction; tolerance and both physical and psychological dependence develop rapidly. psychological dependence develop rapidly.

Morphine is a benzylisoquinoline alkaloid with two additional ring closures.

Systematic (IUPAC) name (5α,6α)-7,8-Systematic (IUPAC) name (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol3,6-diol

IdentifiersIdentifiers CAS numberCAS number 57-27-264-31-3 (neutral 57-27-264-31-3 (neutral

sulfate),52-26-6 (hydrochloride)sulfate),52-26-6 (hydrochloride) ATC code ATC code N02AA01N02AA01 PubChemPubChem 5288826 5288826 DrugBankDrugBank APRD00215 APRD00215 ChemSpider 4450907ChemSpider 4450907 Chemical dataChemical data FormulaFormula C17H19NO3 C17H19NO3 Mol. massMol. mass 285.34 285.34

Pharmacokinetic dataPharmacokinetic data BioavailabilityBioavailability ~25% (oral); 100% (IV);~25% (oral); 100% (IV); Protein bindingProtein binding 30–40%30–40% MetabolismMetabolism Hepatic 90%Hepatic 90% Half lifeHalf life 2–3 h2–3 h ExcretionExcretion Renal 90%, biliary 10%Renal 90%, biliary 10% Therapeutic considerationsTherapeutic considerations Pregnancy cat.Pregnancy cat. C(AU) C(US)C(AU) C(US) Legal statusLegal status Controlled (S8)(AU) Schedule I(CA) Controlled (S8)(AU) Schedule I(CA)

Class A(UK) Schedule II(US)Class A(UK) Schedule II(US)

RoutesRoutes Smoked/inhaled, insufflated, Smoked/inhaled, insufflated, Oral, SC, IM,Oral, SC, IM,

SOURCESOURCE

REGIONAL REGIONAL DISTRIBUTIONDISTRIBUTION

Morphine can be used:Morphine can be used: as an analgesic in hospital settings to relieve as an analgesic in hospital settings to relieve pain in myocardial infarctionpain in myocardial infarction pain in sickle cell crisispain in sickle cell crisis pain associated with surgical conditions, pre- and pain associated with surgical conditions, pre- and

postoperativelypostoperatively pain associated with traumapain associated with trauma in the relief of severe chronic pain, e.g., in the relief of severe chronic pain, e.g., cancercancer pain from kidney stones (renal colic, pain from kidney stones (renal colic,

ureterolithiasis)ureterolithiasis) severe back painsevere back pain

as an adjunct to general anesthesiaas an adjunct to general anesthesia in epidural anesthesia or intrathecal analgesiain epidural anesthesia or intrathecal analgesia for palliative care (i.e., to alleviate pain without for palliative care (i.e., to alleviate pain without

curing the underlying reason for it, usually because curing the underlying reason for it, usually because the latter is found impossible)the latter is found impossible)

as an antitussive for severe coughas an antitussive for severe cough in nebulized form, for treatment of dyspnea, in nebulized form, for treatment of dyspnea,

although the evidence for efficacy is slim. Evidence although the evidence for efficacy is slim. Evidence is better for other routes.is better for other routes.

as an antidiarrheal in chronic conditions (e.g., for as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS, although loperamide diarrhea associated with AIDS, although loperamide (a non-absorbed opioid acting only on the gut) is the (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea).most commonly used opioid for diarrhea).

Effects on Human Effects on Human PerformancePerformance

Most reviews conclude that opioids produce minimal Most reviews conclude that opioids produce minimal impairment of human performance on tests of sensory, impairment of human performance on tests of sensory, motor, or attentional abilities. However, recent studies motor, or attentional abilities. However, recent studies have been able to show some impairments caused by have been able to show some impairments caused by morphine, which is not surprising given that morphine is a morphine, which is not surprising given that morphine is a central nervous system depressant. Morphine has resulted central nervous system depressant. Morphine has resulted in impaired functioning on critical flicker frequency (a in impaired functioning on critical flicker frequency (a measure of overall CNS arousal) and impaired measure of overall CNS arousal) and impaired performance on the Maddox Wing test (a measure of performance on the Maddox Wing test (a measure of deviation of the visual axes of the eyes). Few studies have deviation of the visual axes of the eyes). Few studies have investigated the effects of morphine on motor abilities; a investigated the effects of morphine on motor abilities; a high dose of morphine can impair finger tapping and the high dose of morphine can impair finger tapping and the ability to maintain a low constant level of isometric force ability to maintain a low constant level of isometric force (ie. fine motor control is impaired), though no studies have (ie. fine motor control is impaired), though no studies have shown a correlation between morphine and gross motor shown a correlation between morphine and gross motor abilities abilities

Effects on Human Effects on Human PerformancePerformance

In terms of cognitive abilities, one study has In terms of cognitive abilities, one study has shown that morphine may have a negative shown that morphine may have a negative impact on anterograde and retrograde impact on anterograde and retrograde memory, but these effects are minimal and memory, but these effects are minimal and are transient. Overall, it seems that acute are transient. Overall, it seems that acute doses of opioids in non-tolerant subjects doses of opioids in non-tolerant subjects produce minor effects in some sensory and produce minor effects in some sensory and motor abilities, and perhaps also in attention motor abilities, and perhaps also in attention and cognition. It is likely that the effects of and cognition. It is likely that the effects of morphine will be more pronounced in opioid-morphine will be more pronounced in opioid-naive subjects than chronic opioid users naive subjects than chronic opioid users

Effects on Human Effects on Human PerformancePerformance

In chronic opioid users, such as those on Chronic In chronic opioid users, such as those on Chronic Opioid Analgesic Therapy (COAT) for managing Opioid Analgesic Therapy (COAT) for managing severe, chronic pain, behavioural testing has shown severe, chronic pain, behavioural testing has shown normal functioning on perception, cognition, normal functioning on perception, cognition, coordination and behaviour in most cases. One coordination and behaviour in most cases. One recent study[38] analysed COAT patients in order to recent study[38] analysed COAT patients in order to determine whether they were able to safely operate determine whether they were able to safely operate a motor vehicle. The findings from this study suggest a motor vehicle. The findings from this study suggest that stable opioid use does not significantly impair that stable opioid use does not significantly impair abilities inherent in driving (this includes physical, abilities inherent in driving (this includes physical, cognitive and perceptual skills). COAT patients cognitive and perceptual skills). COAT patients showed rapid completion of tasks which require showed rapid completion of tasks which require speed of responding for successful performance (eg. speed of responding for successful performance (eg. Rey Complex Figure Test) but made more errors Rey Complex Figure Test) but made more errors than controls. COAT patients showed no deficits in than controls. COAT patients showed no deficits in visual-spatial perception and organization (as shown visual-spatial perception and organization (as shown in the WAIS-R Block Design Test) but did show in the WAIS-R Block Design Test) but did show impaired immediate and short-term visual memory impaired immediate and short-term visual memory (as shown on the Rey Complex Figure Test – Recall). (as shown on the Rey Complex Figure Test – Recall).

Effects on Human Effects on Human PerformancePerformance

These patients showed no impairments in These patients showed no impairments in higher order cognitive abilities (ie. higher order cognitive abilities (ie. Planning). COAT patients appeared to have Planning). COAT patients appeared to have difficulty following instructions and showed difficulty following instructions and showed a propensity towards impulsive behaviour, a propensity towards impulsive behaviour, yet this did not reach statistical significance. yet this did not reach statistical significance. Importantly, this study reveals that COAT Importantly, this study reveals that COAT patients have no domain-specific deficits, patients have no domain-specific deficits, which supports the notion that chronic which supports the notion that chronic opioid use has minor effects on psychomotor, opioid use has minor effects on psychomotor, cognitive, or neuropsychological functioning.cognitive, or neuropsychological functioning.

EFFECTS OF MORPHINEEFFECTS OF MORPHINE

IT ACTS ON CNS CAUSING FIRST IT ACTS ON CNS CAUSING FIRST A STIMULATION AND LATER A A STIMULATION AND LATER A DEPRESSION FOLLOWED BY DEPRESSION FOLLOWED BY NARCOSIS.NARCOSIS.

THE EFFECTS CAN BE THE EFFECTS CAN BE DESCRIBED IN 3 STAGES.DESCRIBED IN 3 STAGES.

1.1. EXCITEMENTEXCITEMENT2.2. STUPORSTUPOR3.3. NARCOSISNARCOSIS

EXCITMENTEXCITMENT

THIS STAGE IS ABSENT IF THE DOSE THIS STAGE IS ABSENT IF THE DOSE TAKEN IS LARGE.TAKEN IS LARGE.

IN ADULTS,THERE IS A SENSE OF IN ADULTS,THERE IS A SENSE OF WELL BEING OF BRIEF WELL BEING OF BRIEF DURATION,LAUGHTER,HALLUCINATDURATION,LAUGHTER,HALLUCINATION, AND RAPID HEART RATE ION, AND RAPID HEART RATE OCCUR.OCCUR.

IN CHILDREN,CONVULSIONS MAY IN CHILDREN,CONVULSIONS MAY OCCUR.OCCUR.

STUPORSTUPOR IT IS CHARACTERISED BYIT IS CHARACTERISED BY1.1. HEADACHEHEADACHE2.2. WEARINESSWEARINESS3.3. GIDDINESSGIDDINESS4.4. A SENSE OF WEIGHT IN THE LIMBSA SENSE OF WEIGHT IN THE LIMBS5.5. DIMINISHED SENSIBILITYDIMINISHED SENSIBILITY6.6. STRONG TENDENCY TO SLEEPSTRONG TENDENCY TO SLEEP7.7. PUPILS CONTRACTED,FACE AND LIPS PUPILS CONTRACTED,FACE AND LIPS

CYANOSED,ITCHING SENSATION FELT CYANOSED,ITCHING SENSATION FELT ALL OVER THE SKINALL OVER THE SKIN

8.8. THE PULSE AND RESPIRATION ARE THE PULSE AND RESPIRATION ARE ALMOST NORMALALMOST NORMAL

NARCOSISNARCOSIS

1.1. DEEP COMADEEP COMA2.2. MUSCLES RELAXEDMUSCLES RELAXED3.3. REFLEXES ABOLISHEDREFLEXES ABOLISHED4.4. PUPILS CONTRACTED TO PIN POINT PUPILS CONTRACTED TO PIN POINT

AND NO RESPONSE TO LIGHTAND NO RESPONSE TO LIGHT5.5. BP FALLS,PULSE RAPID AND FEEBLEBP FALLS,PULSE RAPID AND FEEBLE6.6. BREATHING SLOW,GRADUALLY BREATHING SLOW,GRADUALLY

DIMINISHING IN RATEDIMINISHING IN RATE7.7. SKIN IS COLD WITH PERSPIRATIONSKIN IS COLD WITH PERSPIRATION8.8. HYPOTHERMIAHYPOTHERMIA

IN FATAL TERMINATION,THERE IS IN FATAL TERMINATION,THERE IS 1.1. MARKED CYANOSISMARKED CYANOSIS2.2. FROTH ESCAPE FROM MOUTHFROTH ESCAPE FROM MOUTH3.3. BREATHING IS SIGHING AND IRREGULAR BREATHING IS SIGHING AND IRREGULAR

(chyne stokes type)(chyne stokes type)4.4. BREATHING RATE IS 2-4 PER MINUTEBREATHING RATE IS 2-4 PER MINUTE5.5. PULSE IS IMPERSCEPTIBLEPULSE IS IMPERSCEPTIBLE6.6. PUPILS DILATE TERMINALLY, WHEN PUPILS DILATE TERMINALLY, WHEN

ASPHYXIA ENSUES, BUT DO NOT REACT TO ASPHYXIA ENSUES, BUT DO NOT REACT TO LIGHTLIGHT

COMA DEEPENES AND DEATH REASULTS COMA DEEPENES AND DEATH REASULTS FROM ASPHYXIA DUE TO RESPIRATORY FROM ASPHYXIA DUE TO RESPIRATORY PARALYSISPARALYSIS

THE BREATH MAY SMELL OF OPIUM THE BREATH MAY SMELL OF OPIUM THROUGHOUT THE ILLNESSTHROUGHOUT THE ILLNESS

FATAL DOSEFATAL DOSE

IN PERSON NOT ADDICTED TO IN PERSON NOT ADDICTED TO OPIUM, 200mg OF MORPHINE, OR OPIUM, 200mg OF MORPHINE, OR ITS EQUIVALENT OF OPIUM 2gm ITS EQUIVALENT OF OPIUM 2gm IS FATALIS FATAL

10ml OF OPIUM IS REGARDED AS 10ml OF OPIUM IS REGARDED AS DANGEROUS DOSEDANGEROUS DOSE

THE FATAL DOSE OF TINCTURE THE FATAL DOSE OF TINCTURE OF OPIUM IN CHILDREN IS 2-3 OF OPIUM IN CHILDREN IS 2-3 DROPSDROPS

FATAL PERIODFATAL PERIOD

THE USUAL FATAL PERIOD IS THE USUAL FATAL PERIOD IS ABOUT 9-12 HOURSABOUT 9-12 HOURS

ABUSESABUSES The euphoria, comprehensive alleviation of The euphoria, comprehensive alleviation of

distress and therefore all aspects of suffering, distress and therefore all aspects of suffering, promotion of sociability and empathy, "body promotion of sociability and empathy, "body high", and anxiolysis provided by narcotic drugs high", and anxiolysis provided by narcotic drugs including the opioids can cause the use of high including the opioids can cause the use of high doses in the absence of pain for a protracted doses in the absence of pain for a protracted period, which can impart a morbid craving for period, which can impart a morbid craving for the drug in the user. Being the prototype of the the drug in the user. Being the prototype of the entire opioid class of drugs means that entire opioid class of drugs means that morphine has properties that may lend it to morphine has properties that may lend it to misuse. Morphine addiction is the model upon misuse. Morphine addiction is the model upon which the current perception of addiction is which the current perception of addiction is based.based.

ABUSESABUSES Animal and human studies and clinical experience Animal and human studies and clinical experience

back up the contention that morphine is one of the back up the contention that morphine is one of the most euphoric of drugs, and via all but the IV route most euphoric of drugs, and via all but the IV route heroin and morphine cannot be distinguished heroin and morphine cannot be distinguished according to studies. Chemical changes to the according to studies. Chemical changes to the morphine molecule yield other powerful euphorigenics morphine molecule yield other powerful euphorigenics such as dihydromorphine, hydromorphone (Dilaudid®, such as dihydromorphine, hydromorphone (Dilaudid®, Hydal®) and oxymorphone (Numorphan®, Opana®) Hydal®) and oxymorphone (Numorphan®, Opana®) as well as the latter three's methylated equivalents as well as the latter three's methylated equivalents dihydrocodeine, hydrocodone and oxycodone dihydrocodeine, hydrocodone and oxycodone respectively; in addition to heroin, there are respectively; in addition to heroin, there are dipropanoylmorphine, diacetyldihydromorphine and dipropanoylmorphine, diacetyldihydromorphine and other members of the 3,6 morphine diester category other members of the 3,6 morphine diester category like nicomorphine and other similar semi-synthetic like nicomorphine and other similar semi-synthetic opiates like desomorphine, hydromorphinol &c. used opiates like desomorphine, hydromorphinol &c. used clinically in many countries of the world but in many clinically in many countries of the world but in many cases also produced illicitly in rare instances cases also produced illicitly in rare instances

ABUSESABUSES Misuse of morphine generally entails taking more than Misuse of morphine generally entails taking more than

prescribed or outside of medical supervision, injecting prescribed or outside of medical supervision, injecting oral formulations, mixing it with unapproved oral formulations, mixing it with unapproved potentiators such as alcohol, cocaine, and the like, potentiators such as alcohol, cocaine, and the like, and/or defeating the extended-release mechanism by and/or defeating the extended-release mechanism by chewing the tablets or turning into a powder for chewing the tablets or turning into a powder for snorting or preparing injectables. The latter method snorting or preparing injectables. The latter method can be every bit as time-consuming and involved as can be every bit as time-consuming and involved as traditional methods of smoking opium. This and the traditional methods of smoking opium. This and the fact that the liver destroys a large percentage of the fact that the liver destroys a large percentage of the drug on the first pass impacts the demand side of the drug on the first pass impacts the demand side of the equation for clandestine re-sellers, as many customers equation for clandestine re-sellers, as many customers are not needle users and may have been disappointed are not needle users and may have been disappointed with ingesting the drug orally. As morphine is with ingesting the drug orally. As morphine is generally as hard or harder to divert than oxycodone generally as hard or harder to divert than oxycodone in a lot of cases, morphine in any form is uncommon in a lot of cases, morphine in any form is uncommon on the street, although ampoules and phials of on the street, although ampoules and phials of morphine injection, pure pharmaceutical morphine morphine injection, pure pharmaceutical morphine powder, and soluble multi-purpose tablets are very powder, and soluble multi-purpose tablets are very popular where available popular where available

ABUSESABUSES Morphine is also available in a paste which is Morphine is also available in a paste which is

used in the production of heroin which can be used in the production of heroin which can be smoked by itself or turned to a soluble salt and smoked by itself or turned to a soluble salt and injected; the same goes for the penultimate injected; the same goes for the penultimate products of the Kompot (Polish Heroin) and products of the Kompot (Polish Heroin) and black tar processes. Poppy straw as well as black tar processes. Poppy straw as well as opium can yield morphine of purity levels opium can yield morphine of purity levels ranging from poppy tea to near-pharmaceutical ranging from poppy tea to near-pharmaceutical grade morphine by itself or with all of the more grade morphine by itself or with all of the more than 50 other alkaloids. It also is the active than 50 other alkaloids. It also is the active narcotic ingredient in opium and all of its narcotic ingredient in opium and all of its forms, derivatives, and analogues as well as forms, derivatives, and analogues as well as forming from breakdown of heroin and forming from breakdown of heroin and otherwise being present in many batches of otherwise being present in many batches of illicit heroin as the result of imcomplete illicit heroin as the result of imcomplete acetylation.acetylation.

ABUSESABUSES Slang terms for morphine include M, Big M, Slang terms for morphine include M, Big M,

Vitamin M, Miss Emma, morph, morpho, Vitamin M, Miss Emma, morph, morpho, Murphy, cube, cube juice, White Nurse, Red Murphy, cube, cube juice, White Nurse, Red Cross, mojo, hocus, 13, Number 13, mofo, Cross, mojo, hocus, 13, Number 13, mofo, unkie, happy powder, joy powder, first line, unkie, happy powder, joy powder, first line, Aunt Emma, coby, em, emsel, morf, dope, glad Aunt Emma, coby, em, emsel, morf, dope, glad stuff, goody, God's Medicine, God's Own stuff, goody, God's Medicine, God's Own Medicine, hard stuff, morfa, morphia, morphy, Medicine, hard stuff, morfa, morphia, morphy, mud, sister, Sister Morphine, stuff, white stuff, mud, sister, Sister Morphine, stuff, white stuff, white merchandise and others. MS-Contin and white merchandise and others. MS-Contin and its equivalents in other countries are known as its equivalents in other countries are known as misties, blockbusters, and the 100 mg tablets misties, blockbusters, and the 100 mg tablets as greys.as greys.

RELATED TERMSRELATED TERMS

DRUG ADDICTIONDRUG ADDICTION

HEROINHEROIN

GLUE SNIFFINGGLUE SNIFFING