amphetamines

amphetamines and related substances

history

  • Chinese use stimulant ephedra (ma huang) containing the alkaloids ephedrine & pseudoephedrine for over 5000yrs to Rx asthma & URTI.
  • amphetamine 1st synthesised in Germany in 1887 but not used clinically until 1920's following reduced availability of ephedrine to Rx asthma.
  • discovery of dextroamphetamine and metamphetamine / meth / ice soon followed.
  • nasal decongestant containing amphetamine marketed in 1932, but widespread abuse led to FDA banning amphetamine inhalers in 1959.
  • amphetamines were widely used as stimulants during World War II for a variety of conditions including hypotension & obesity.
  • passage of Controlled Substance Act in US in 1970 reduced rates of amphetamine abuse.
  • 'designer' amphetamines created in 1980's for illicit recreational use including the more serotoninergic MDMA (Ecstasy).
  • resurgence of metamphetamine abuse due to production of high purity formulation known as 'ice'.
  • the rave scene of the 1990's brought widespread use of MDMA and ice to Europe, North America, and Australasia.
    • in Australia, use of amphetamines is ~2.9% of 15-64 yr olds, with lifetime use ~7.7% amongst men and ~4.9% amongst women (although lifetime rates in NZ in 2004 were reported at 9%)
  • production of similar piperazine family drugs such as BZP (became a restricted substance in 2008) followed.
    • although BZP and TFMPP are not strictly amphetamines, BZP has actions similar to amphetamine while TFMPP is more similar to MDMA.
  • 4-Bromo-2,5-dimethoxyamphetamine (2CB, MFT, “Nexus”) is a rave drug which produces relaxation, euphoria and altered perception but also severe arterial spasm which has resulted in report on one limb requiring amputation.
  • medicinal amphetamines may be abused:
    • methylphenidate used in Rx of ADHD
    • phentermine used in Rx of obesity

pharmacology

  • amphetamines are derived from the CNS stimulants, phenylethylamines, and have structural similarities to adrenaline.
  • metamphetamine is easily made (although risk of explosions in home labs) through reduction of ephedrine or pseudoephedrine (hence limited OTC availability of these).
  • they are lipophilic weak bases with large Vd & not readily metabolised by MAO or COMT, thus have long durations of actions.
  • eliminated by hepatic biotransformation & urine pH-dependent renal excretion.
  • amphetamines are taken up into neuronal cells via neuronal monoamine reuptake transporters, and also act as a substrate for these transporters, resulting in transporter-mediated neurotransmitter release.
  • desired actions of amphetamine & metamphetamine (Speed/Ice) amongst those who use them recreationally are:
    • euphoria, hyper-stimulation, increased stamina and sex drive and disinhibition, decreased appetite.
  • desired actions of MDMA (Ecstasy) which has more serotoninergic actions, amongst those who use them recreationally are:
    • euphoria, inner peace, social facilitation, heightened sexuality and disinhibition, mild hallucinogen effects
  • acute toxicity is produced by excessive extracellular noradrenaline, dopamine and Serotonin physiology resulting in an alpha-adrenergic and beta-adrenergic sympathomimetic toxidrome.

amphetamine

  • Amp, Bennies, Black beauties, Browns, Cranks, Fives, Goey, Hearts, Louee, Speed, Uppers, Whiz
  • mainly sympathomimetic actions with greater peripheral effects than metamphetamine
  • basic drug with pKa of 9.9, thus alkaline urine reduces excretion and increases half-life to ~20 hours, while acidic urine reduces half life to 5-6 hours
  • generally taken orally but can be inhaled vaporised, or snorted as a fine powder, or injected
  • iv injection produces marked euphoria, clear thinking but inefficient, often reptitious vigorous activity
  • effects may include:
  • users often take “downers” (eg. alcohol, marijuana, benzodiazepines, barbiturates, or opiates and opioids) to offset overstimulation effects
  • there is a rapid fall off in effects which enhances intense craving for the drug which rapidly leads to addiction
  • withdrawal (“crashing”) leads to long periods of sleep, hunger, extreme lethargy, depression, suicidality and anhedonia

dexamphetamine

  • commonly used in Mx of ADHD since the 1990's

lisdexamfetamine

  • introduced in Aust in 2013 as Vyvanse for Mx of ADHD
  • prodrug of dexamphetamine

metamphetamine

  • mainly sympathomimetic actions, most potent cardiovascular effects of all amphetamines, greater CNS effects than amphetamine
  • results in a far higher brain dopamine level than other commonly abused substances
  • crystal meth is becoming the major pyschosocially destructive substance abuse epidemic

3,4-MDMA (ecstasy)

  • 3,4-methylenedioxymetamphetamine
  • Adam, Bart Simpson, Clarity, Disco biscuits, Essence, E, Ecstasy, Love drug, Red and black, White dove, X, XTC
  • usually colourful tablets at 50-200mg per dose
  • most tablets sold in Australia are not actually MDMA but metamphetamine which is simpler to make, and often include contaminants such as cocaine, heroin, ketamine, codeine, paracetamol, ephedrine, pseudoephedrine, caffeine, benzodiazepines, antihistamines and LSD.
  • a more recent development is use of MDMA in powder form (“Molly”) as users perceive that it is more likely to be MDMA
  • users of MDMA in the dance scene are advised to take frequent rest breaks and sip water regularly to rehydrate
  • unwanted effects include jaw clenching, teeth grinding, anxiety, paranoia, confusion, hallucinations, bizarre behaviour, and possibly psychosis.
  • overdose can result in hypertension, tachycardia and hyperthermia, and may be fatal.

2,5-Dimethoxy-4-methylamphetamine

  • Peace, Serenity, Tranquillity

4-Bromo-2,5-dimethoxyamphetamine

  • 2CB, MFT, Nexus
  • extremely potent hallucinogen producing marked psychoactive effects, euphoria, altered perception
  • used impregnated in paper as with LSD

piperazines: BZP & TFMPP

  • Bliss, BNZ, Bolts, Charge, Exodus, Frenzy, Goodstuff, Grins, Herbal Ecstasy, Herbal party pills, Jumps, Kandy, Legal ecstasy, Legal E, Legal X, Nemesis, Red Hearts, Silver bullet.
  • BZP inhibitis reuptake of dopamine & serotonin & stimulates peripheral alpha-2 receptors but exhibits lower potency than amphetamine.
    • seizures, vomiting, collapse, agitation, anxiety & confusion are common in toxicity.
  • TFMPP is more serotoninergic and produces affects similar to MDMA
amphetamines.txt · Last modified: 2014/04/16 13:15 by gary1