In this chapter, you will learn and review high-yield aspects of toxicology and metabolic disease that are frequently tested on board examinations and the RITE®. Real patient pathology and MRI images, flashcards, and a question bank are included for a complete learning experience!

Authors: Steven Gangloff MD, Brian Hanrahan MD

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Drugs of Abuse


  • Alcohol’s mechanism of action is not entirely understood, but it acts as an agonist of gamma-aminobutyric acid (GABA, the primary inhibitory neurotransmitter in the CNS) .
  • Acute intoxication:
    • Presents with slurred speech, incoordination, unsteady gait, and nystagmus.
  • Chronic EtOH:
    • Can cause vitamin deficiencies such as B12 deficiency and B1 deficiency-related Wernicke’s encephalopathy and Wernicke-Korsakoff disease. See below regarding vitamin deficiencies.
    • Subcortical alcohol-related dementia.
    • Cerebellar atrophy

  • Marchiafava-Bignami disease
    • Corpus callosum damage.
    • Presents with a sudden onset of stupor, coma, and seizures. Can also present with dementia, gait problems, psychiatric disturbances, incontinence, hemiparesis, aphasia, and apraxia of the left hand (due to callosal disconnection).


  • Ingested as an alcohol substitute and in suicide attempts.
  • Methanol → formaldehyde → formic acid.
  • Presents with a headache, confusion, hyperventilation and anion gap metabolic acidosis, and visual deficit.
  • Pathology: Necrosis and hemorrhage of the putamen and toxic optic neuropathy.
  • Treatment: bicarbonate and fomepizole are first-line. Ethanol works similarly to fomepizole. Dialysis may also be needed.

Ethylene Glycol

  • Presents with edema and petechial hemorrhages secondary to calcium oxalate deposits within vessels.


  • Presents with nystagmus, hypertension, tachycardia, muscle rigidity, dysarthria, decreased response to pain, and seizures.

Bath salts/methylenedioxypyrovalerone (MDPV)

  • Presents with hypertension, tachycardia, delusions, hallucinations, and violent behavior.


  • Acute overdose will present with miosis (constricted pupils), hypotension, bradycardia, and decreased respirations.
    • Can be treated with naloxone.
  • Constipation can occur with chronic use.
  • Long-term treatment for opioid dependence includes naltrexone (long-acting opioid antagonist), methadone, or buprenorphine.
  • Withdrawal symptoms include lacrimation, rhinorrhea, diaphoresis, mydriasis, and yawning.
    • Clonidine (alpha 2-receptor agonist) can blunt the sympathetic symptoms associated with opioid withdrawal.
  • Meperidine is metabolized into a neurotoxic metabolite that can provoke myoclonus, tremors, and seizures.


  • Mechanism: Increases frequency of GABAA channel opening.
    • Barbiturates, on the other hand, increase the duration of GABAA opening.
  • Most benzodiazepines are metabolized by the cytochrome p450 system.
    • Lorazepam, oxazepam, and temazepam, however, undergo direct glucuronidation without cytochrome p450 metabolism and therefore can be used in patients with renal or hepatic dysfunction with only minor effects on pharmacokinetics.


  • Works by inhibiting dopamine reuptake and increasing dopamine concentrations in the nucleus accumbens. Also inhibits the reuptake of serotonin and norepinephrine.
  • Acute intoxication presents with mydriasis, euphoria, and tachycardia.


  • Amphetamine intoxication presents similarly to cocaine, except the mechanism of action is through both the direct release of dopamine and norepinephrine and the inhibiting of reuptake.

Nitrous Oxide (inhaled)

  • Exam: progressive paresthesias secondary to myelopathy of the posterior and lateral columns, mimicking B12 deficiency. Additional symptoms include ataxia, weakness, and positive Lhermitte’s sign.
  • Pathophysiology: Irreversible oxidization of methylcobalamin which interferes with the vitamin B12-dependent conversion of homocysteine to methionine as well as methyl-malonyl CoA into succinyl CoA. Homocysteine levels will be elevated. Treat with methionine supplementation.

Glue (Toluene)

  • Inhalation of toluene causes myelin damage and diffuse leukoencephalopathy.

“Chasing the Dragon”

  • Inhalation of heated heroin or morphine fumes. Can produce a toxic leukoencephalopathy.

Supplements, Botany, & Foods


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Table of Contents

Table of Contents