Internal Medicine

Amphetamine toxicity

Amphetamines are a subclass of psychostimulants characterised by the presence of a α-methylphenethyl-amine core structure.


Amphetamines are a subclass of psychostimulants characterised by the presence of a α-methylphenethyl-amine core structure.


Synthesized in 1887, amphetamine (1-methyl-2-phenethylamine) was the first member of a group of compounds that have similar structures and biological properties and are collectively called “amphetamines”. The group also includes methamphetamine, synthesized 6 years later, and 3-4-methylenedioxymethamphetamine (MDMA), patented in 1914.

In sum, abuse of amphetamines constitutes a serious public health concern. Amphetamines are the prescription drugs most commonly abused by adolescents and young adults, and illicit amphetamines are second only to marijuana as a form of illicit drug abuse in young adults. Prevalence of problematic use of amphetamines by older adults has also been rising. Emergency department mentions of amphetamines among patients 55 years and older have increased 700% from 1995 to 2002, for example.


  • d-amphetamine (d-AMPH) ‘Speed’
  • Methamphetamine (METH) ‘Ice’
  • 3,4-methylenedioxymethamphetamine (MDMA) ‘Ecstasy’
Amphetamine and congeners. The chemical structures of amphetamines and the congeners are shown as indicated (the chemical names in parentheses represent the IUPAC names): amphetamine [street name: ‘Speed’; d-form: (2S)-1-phenylpropan-2-amine], methamphetamine [street name: ‘crank’ or ‘Crystal meth’; d-form: (2S)-N-methyl-1-phenylpropan-2-amine], 3,4-methylenedioxymethamphetamine or MDMA [street name: ‘Ecstasy’; 1-(1,3-benzodioxol-5-yl)-N-methylpropan-2-amine]. | Steinkellner, T., Freissmuth, M., Sitte, H. H., & Montgomery, T. (2011). The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and D-amphetamine. Biological chemistry, 392(1-2), 103–115.

Mechanism of action

Amphetamines produce their principal effects by increasing synaptic levels of the biogenic amines, dopamine, norepinephrine and serotonin, through multiple mechanisms.

Medical use:

Both drugs are classified by the Drug Enforcement Agency (DEA) as belonging in Schedule II, having accepted medical uses but being tightly controlled because of their potential for abuse that can lead to severe psychological and physiological dependence.
  • Amphetamine: Attention deficit-hyperactivity disorder (ADHD) & narcolepsy
  • Methamphetamine: ADHD and obesity

Clinical features

  • Sympathomimetic effects: Dry mouth, hyperthermia, dilated pupils, tachypnea, with increased alertness and energy.
  • CNS stimulation: Altered mental status, hyperactivity, agitation, confusion, and gross psychosis with paranoia requiring chemical and physical restraints
  • CVS effects (severe cases): Chest pain, palpitations, tachycardia, dysrhythmias, hypertensive emergencies, and stroke.
  • Cutaneous effects: Skin flushing and other cutaneous findings include any track marks cellulitis or abscesses


Amphetamine toxicity is a clinical diagnosis and some of the key features to look for are agitation, hyperthermia, tachycardia, hypertension, and diaphoresis.

Lab studies:

  • Complete blood count (CBC)
  • Comprehensive metabolic panel
  • Serum creatinine kinase levels
  • Urinalysis (if needed)


Patient acutely intoxicated on amphetamines will require chemical and physical restraints to prevent self-harm or harm to others, as these patients can be hostile with severe paranoia. Some life-threatening signs and symptoms need to be addressed on an emergent basis such as trauma, compromised airway, seizures, and any cardiac dysrhythmias.

Supportive managemnet:

A patient can be treated with supportive therapy with sedation and observation if there are no life-threatening signs and symptoms.
  • Benzodiazepines: For sedation and to control seizures
  • Activated charcoal (if conscious and able to take it orally): Reduce amphetamine absorption in the digestive tract
  • Fluids: To treat dehydration

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