Dextroamphetamine - Revision history

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Sharon: Created page with "== Also known as == CCC, Dex, Poor Man's PCP, Robo, Rojo, Skittles, Triple C, Velvet, Dexedrine, Dexedrine Spansules, Dextrostat, Liquadd, ProCentra, Zenzedi == Classificati..."

2017-04-27T19:50:36Z

Created page with "== Also known as == CCC, Dex, Poor Man's PCP, Robo, Rojo, Skittles, Triple C, Velvet, Dexedrine, Dexedrine Spansules, Dextrostat, Liquadd, ProCentra, Zenzedi == Classificati..."

New page

== Also known as ==

CCC, Dex, Poor Man's PCP, Robo, Rojo, Skittles, Triple C, Velvet, Dexedrine, Dexedrine Spansules, Dextrostat, Liquadd, ProCentra, Zenzedi

== Classification ==

[[CNS]] Stimulants
[[Category:Stimulants]]
== Medical usage ==

Dextroamphetamine is used to treat narcolepsy and [[ADHD]] <ref name="1a">'''Dextroamphetamine''', 2017, https://www.drugs.com/cdi/dextroamphetamine.html</ref>.

== How long do its effects last? ==
=== Onset of effects ===

* Immediate release - 30 - 90 minutes
* Extended release - 90 - 120 minutes <ref name="2a">'''Dextroamphetamine''', 2017, https://en.wikipedia.org/wiki/Dextroamphetamine</ref>.

=== Duration of effects ===

* Immediate release dosing - 3 - 7 hours,
* Extended release dosing - 12 hours <ref name="2a"/>.

== Pharmacology ==

In the [[CNS]] dextroamphetamine induces the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, resulting in measurable behavioural changes such as euphoria. As a [[CNS]] [[stimulant]], this agent may increase blood pressure and reduce appetite. Similar to other amphetamines, dextroamphetamine has a high potential for abuse, dependence, and addiction if used in large doses over extended periods of time <ref name="3a">'''Dextroamphetamine (Code C28981)''', 2017, https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C28981</ref>, <ref name="4a">'''Dextroamphetamine''', 2017, https://pubchem.ncbi.nlm.nih.gov/compound/dextroamphetamine</ref>.

=== Pharmacodynamics ===

Amphetamines such as dextroamphetamine are noncatecholamine, sympathomimetic amines with [[CNS]] stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioural effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system <ref name="5a">'''Dextroamphetamine''', 2017, https://www.drugbank.ca/drugs/DB01576</ref>.

=== Bioavailability ===

Oral bioavailability is over 75% <ref name="5a"/>.

=== Metabolism ===

Hepatic <ref name="5a"/>.

=== Half-life ===

10 - 28 hours (average is approximately 12 hours) <ref name="5a"/>.

=== Elimination ===

Renal 45% <ref name="2a"/>.

=== Lethal dosage ===

In rats, the oral [[LD50]] of dextroamphetamine sulfate is 96.8 mg/kg <ref name="5a"/>. The acute lethal dose in adults has been reported at 20 - 25 mg/kg, and in children, 5 mg/kg. Death from as little as 1.5 mg/kg in an adult has also been noted <ref name="6a">Gossel, T. A. and Bricker, J. D., '''Principles of Clinical Toxicology''', 1994, 3rd edition, Raven Press, Ltd., New York, NY, 348</ref>, <ref name="4a"/>.

=== Toxicity ===

Fatigue and depression usually follow the central stimulation <ref name="5a"/>. Toxic amphetamine blood concentration: 50 ug/dL; Lethal amphetamine blood concentration: 200 ug/dL <ref name="6a"/>.

=== Tolerance ===

Psychological dependence often occurs when dextroamphetamine is used chronically. Tolerance almost invariably develops to the anorexigenic effect of amphetamines, and is often seen also in the need for increasing doses to maintain improvement of mood in psychiatric patients. Tolerance is striking in individuals who are dependent on the drug, and a daily intake of 1700 mg without apparent ill effects has been reported. Development of tolerance is not invariable, and cases of narcolepsy have been treated for years without requiring an increase in the initially effective dose <ref name="7a">Gilman, A. G. and Goodman, L. S. and A. Gilman, A., '''Goodman and Gilman's The Pharmacological Basis of Therapeutics''', 1985, 7th edition, Macmillan Publishing Co., Inc., New York, 168</ref>, <ref name="4a"/>.

=== Mechanism of action ===

The exact mechanism of action is not known. Dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dosages, it causes release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems by reversal of the monoamine transporters. Dextroamphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect <ref name="5a"/>.

=== GHS Classification ===









[[File:GHS02.jpg|center|border]] [[File:GHS05.jpg|center|border]] [[File:GHS06.jpg|center|border]]

Aggregated [[GHS]] information from 2 notifications provided by 24 companies to the ECHA C&L Inventory. Each notification may be associated with multiple companies <ref name="4a"/>.

* H226 (100%): Flammable liquid and vapour [Warning Flammable liquids - Category 3],
* H300 (95.83%): Fatal if swallowed [Danger Acute toxicity, oral - Category 1, 2]m
* H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation - Category 1A, B, C] <ref name="4a"/>.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from all companies. Only Hazard Codes with percentage values above 10% are shown <ref name="4a"/>.

== Signs of usage ==

* rapid heartbeat,
* reduced appetite or weight loss,
* tremors,
* sleep difficulty,
* dry mouth,
* mood swings,
* verbal tics,
* hostility,
* paranoia,
* hallucinations,
* erratic behaviour,
* tolerance,
* withdrawal symptoms when attempting to cut down use <ref name="8a">Miller, L., '''Dextroamphetamine Abuse''', 2017, http://drugabuse.com/library/dextroamphetamine-adhd-drug/</ref>.

The user may have a persistent runny nose or nosebleeds if the pills are crushed and snorted. A user may have needle or "track" marks if he or she injects the pills <ref name="8a"/>.

== Effects ==
=== Minor ===

Incidence not known -

* bad, unusual, or unpleasant (after) taste,
* change in taste,
* constipation,
* decreased interest in sexual intercourse,
* dry mouth,
* hives or welts, itching, or skin rash,
* inability to have or keep an erection,
* indigestion,
* loss in sexual ability, desire, drive, or performance,
* passing of wind,
* redness of the skin,
* weight loss <ref name="1a"/>.

=== Major ===

==== Rare ====
* agitation,
* delusions,
* hallucinations <ref name="1a"/>.

==== Incidence not known ====

* blurred vision,
* chest discomfort or pain,
* difficulty breathing,
* dizziness,
* faintness,
* false or unusual sense of well-being,
* fast, pounding, or irregular heartbeat or pulse,
* headache,
* pounding in the ears,
* shakiness in the legs, arms, hands, or feet,
* oedema,
* trembling or shaking of the hands or feet,
* troubled breathing,
* twitching, twisting, or uncontrolled repetitive movements of tongue, lips, face, arms, or legs,
* insomnia,
* uncontrolled vocal outbursts and/or tics (uncontrolled repeated body movements),
* unusual tiredness or weakness <ref name="1a"/>.

**** Serious

* difficulty thinking clearly,
* impaired memory,
* unhealthy weight loss,
* malnutrition,
* [[hypertension]],
* [[tachycardia]],
* impaired eyesight,
* psychotic symptoms,
* tremors,
* seizures (highest risk in patients with seizure history),
* heart attack,
* stroke,
* death <ref name="8a"/>.

**** Abuse

* increased energy,
* heightened focus,
* increased alertness,
* suppressed appetite,
* feelings of euphoria <ref name="8a"/>.

**** Overdose

* change in consciousness,
* dark-coloured urine,
* diarrhoea,
* discouragement,
* feeling sad or empty,
* fever,
* irritability,
* lack of appetite,
* loss of consciousness,
* loss of interest or pleasure,
* mood or mental changes,
* muscle cramps or spasms,
* muscle pain or stiffness,
* nausea,
* panic state,
* physical attempt to injure,
* rapid breathing,
* seizures,
* stomach cramps,
* sweating,
* trouble concentrating,
* violent actions,
* vomiting <ref name="9a">'''Dextroamphetamine (Oral Route)''', 2017, http://www.mayoclinic.org/drugs-supplements/dextroamphetamine-oral-route/description/drg-20071795</ref>.

*** History

Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as GlaxoSmithKline) introduced it in the form of the Benzedrine inhaler for use as a bronchodilator. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base, not a chloride or sulfate salt.

Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dextroamphetamine, and in 1937 Smith, Kline, and French introduced tablets under the tradename Dexedrine. In the United States, Dexedrine was approved to treat narcolepsy, attention disorders, and obesity. In Canada indications once included epilepsy and parkinsonism <ref name="11a">'''Dextroamphetamine''', 2005, https://web.archive.org/web/20060427084347/http://www.mentalhealth.com/drug/p30-d04.html</ref>. Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950's, an extended release capsule (the "Spansule"). Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue <ref name="10a">Heal, D. J. and Smith, S. L. and Gosden, J. and Nutt, D. J., '''Amphetamine, past and present - a pharmacological and clinical perspective''', ''Journal of Psychopharmacology'', 2013, 27, 6, 479-496, https://dx.doi.org/10.11772F0269881113482532, https://www.ncbi.nlm.nih.gov/pubmed/23539642</ref>.

It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for misuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use. Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain) <ref name="12a">Sittig, M., '''Pharmaceutical Manufacturing Encyclopedia''', 1988, 2nd edition, William Andrew Publishing/Noyes, ISBN 978-0-8155-1144-1, http://www.knovel.com/web/portal/browse/display?_EXT_KNOVEL_DISPLAY_bookid=598</ref>.

In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma) <ref name="2a"/>.

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== References ==

<references />

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