AMP

• LSD


  Lysergic acid diethylamide, invented in 1938 by Albert Hofmann
• CIA research on LSD

  • Designed a study to determine optimal dosage levels for interrogation
  • Investigated the potential of LSD to act as a truth serum
  • Noted that LSD aided in the recovery of repressed memories
• LSD


  Stimulates the neurotransmitter serotonin, producing hallucinations and dissociating the user from reality
• Mechanism of LSD hallucinations

  Not known
• Mechanism of LSD toxicity

  Stimulates 5-HT2 receptors, alters the activity of serotonin and dopamine in the brain
• Toxic dose of LSD

  Paranoia or panic attacks may occur with any dose, the toxic dose may be only slightly greater than the recreational dose
• Mild to moderate LSD intoxication

  Anxious and fearful, paranoid or bizarre reasoning, tearful, or self-destructive. Sympathomimetic side effects like tachycardia, mydriasis, diaphoresis, hyperreflexia, hypertension, and fever
• Life-threatening LSD toxicity


  Intense sympathomimetic stimulation can cause seizures, severe hyperthermia, hypertension, intracranial hemorrhage and cardiac arrhythmias
• Diagnosis of LSD intoxication

  History of use and the presence of signs of sympathetic stimulation. Serum drug levels are neither widely available nor clinically useful in emergency management. In hyperthermic patients, obtain prothrombin time, CPK, and urinalysis dipstick for occult blood (myoglobinuria will be positive)
• Emergency and supportive measures for LSD intoxication

  1. Treat agitation or severe anxiety states with diazepam or midazolam

  2. Haloperidol are useful despite a small theoretic risk of lowering the seizure threshold

  3. Treat seizures, hyperthermia, rhabdomyolysis, hypertension and cardiac arrhythmias
• Antidote for LSD


  There is no specific antidote. Sedating doses of diazepam may alleviate anxiety, and hypnotic doses can induce sleep for the duration of the "trip"
• Decontamination for LSD


  Administer activated charcoal if available. Do not induce vomiting, because it is relatively ineffective and is likely to aggravate psychological distress. May induce seizures. In hospital, administer activated charcoal. No need for gastric lavage, unless massive ingestion is suspected or the person is unable or unwilling to ingest the charcoal
• Enhanced elimination for LSD

  Not useful. Urinary acidification does not enhance total-body elimination and may aggravate myoglobinuric renal failure
• Amphetamine-related drugs


  • Amphetamine
  • Methamphetamine
  • Methylene-dioxy-met-amphetamine (MDMA, ecstasy, XTC)
  • Methylphenidate
  • Atomoxetine
• How methamphetamine is used

  • Injected
  • Snorted
  • Smoked
  • Orally
• Mechanism of toxicity of amphetamines

  Activate the sympathetic nervous system, induce peripheral release of catecholamines, inhibition of neuronal reuptake of catecholamines, and inhibition of monoamine oxidase. Some also cause serotonin release and block neuronal serotonin uptake. It both CAUSES nerves to fire and AMPLIFIES existing nerve activity
• Toxicokinetics of amphetamines


  Well absorbed orally, have large volumes of distribution (Vd = 3–33 L/kg), extensively metabolized by the liver, excretion highly dependent on urine pH and eliminated more rapidly in an acidic urine
• Short-term effects of methamphetamine

  Psychological: Confidence, alertness, mood, sex drive, energy, talkativeness, boredom, loneliness, timidity. Physical: Heart rate, respiration, blood pressure, pupil size, sensory acuity, energy, appetite, sleep, reaction time
• There is convincing evidence in humans and animals, both by imaging and behavioral studies, that brain damage occurs with methamphetamine use
• Behavioral consequences of methamphetamine use

  Attention, verbal learning, memory, decision making are all impaired during early abstinence. After 8 months abstinence, still slow on some tasks. Headaches and depression may not improve, and there may be ongoing cognitive impairment
• Toxicity of amphetamines


  Low therapeutic index, with toxicity at levels only slightly above usual doses, but high degree of tolerance
• Toxic effects of amphetamines

  Death may be caused by ventricular arrhythmia, seizures, intracranial hemorrhage or hyperthermia. Hyperthermia results from seizures and muscular hyperactivity (cause rhabdomyolysis) and drug-induced vasoconstriction (especially in athletes abusers prior to race)
• Diagnosis of amphetamine intoxication

  History of amphetamine use, clinical features of sympathomimetic drug intoxication, urine samples confirmation of exposure. Serum levels not available and do not correlate well with severity of clinical effects
• Drugs that can produce a positive result on amphetamine tests


  Selegiline is metabolized to l-amphetamine and l-methamphetamine, Clobenzorex (an anorectic drug sold in Mexico) is metabolized to amphetamine
• Emergency and supportive measures for amphetamine intoxication


  Treat ABC, agitation, seizures, coma, and hyperthermia if they occur. Continuously monitor the temperature, other vital signs, and the ECG for a minimum of 6 hours. Agitation: benzodiazepines usually satisfactory, antipsychotics (haloperidol, olanzapine) may be needed. Hypertension best treated with sedation, if not effective use a parenteral vasodilator (phentolamine or nitroprusside). Treat tachyarrhythmias with propranolol or esmolol
• Decontamination for amphetamine intoxication

  Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions
• Enhanced elimination for amphetamine intoxication

  Dialysis and hemoperfusion are not effective. Renal elimination may be enhanced by urine acidification, but not recommended as it may aggravate nephrotoxicity of myoglobinuria