Psychoactive Drugs: Intoxication & Withdrawal

Psychoactive Drug Intoxication and Withdrawal

• Depressants:

  • Intoxication: Mood elevation, decreased anxiety, sedation, behavioral disinhibition, respiratory depression
  • Withdrawal: Anxiety, tremors, seizures, insomnia

• Alcohol (Ethanol):

  • MOA: GABA agonist, glutamate antagonist (GABA-A receptor positive allosteric modulator)
  • Intoxication: Emotional lability, slurred speech, ataxia, coma, blackouts, disinhibition, increased AST (2x ALT)
  • Treatment: Supportive care (fluids, antiemetics)

• Medication for Alcohol Withdrawal:

  • Disulfiram:

    • MOA: Inhibits ALDH, increasing acetaldehyde after drinking, reinforcing abstinence
    • Usual Dose: 250 mg/day (range 125-500 mg/day)

  • Naltrexone:

    • MOA: μ-opioid receptor antagonist, reduces feelings of reward and craving
    • Usual Dose: 50 mg/day

  • Acamprosate:

    • MOA: Unknown mechanism, may block hyperglutamatergic state, mild protracted abstinence syndromes with feelings of "need" for alcohol
    • Usual Dose: 666 mg three times daily

Barbiturates

• MOA: Increases duration of chloride channel opening (GABA-A receptor positive allosteric modulator)
• Intoxication: Low safety margin, marked respiratory depression
• Withdrawal: Delirium, life-threatening cardiovascular collapse
• Treatment: Symptom management (assist respiration, increase blood pressure)

Benzodiazepines

• MOA: Increases frequency of chloride channel opening (GABA-A receptor positive allosteric modulator)
• Intoxication: Greater safety margin, ataxia, minor respiratory depression
• Treatment: Flumazenil (benzodiazepine receptor antagonist)
• Withdrawal: Seizures, sleep disturbance, depression

Opioids

• MOA: Mu, Kappa, and Delta-Opioid receptor agonists (Opioid receptor modulator)
• Intoxication: Pinpoint pupils, decreased GI motility, respiratory and CNS depression, euphoria, decreased gag reflex, seizures
• Treatment: Naloxone (for overdose)
• Withdrawal: Dilated pupils, diarrhea, flu-like symptoms, rhinorrhea, yawning, nausea, sweating, piloerection, lacrimation
• Treatment: Symptom management, methadone, buprenorphine

Inhalants

• MOA: Enhanced GABA signaling
• Intoxication: Disinhibition, euphoria, slurred speech, ataxia, disorientation, drowsiness, perinasal/perioral rash
• Withdrawal: Irritability, dysphoria, sleep disturbance, headache

Stimulants

• Intoxication (nonspecific): Mood elevation, decreased appetite, psychomotor agitation, insomnia, cardiac arrhythmias, tachycardia, anxiety
• Withdrawal (nonspecific): Irritability, dysphoria, sleep disturbance, headache

Amphetamines

• MOA: Induces reversal of monoamine transporters (VMAT, DAT, SERT, NET), increases neurotransmitter release
• Intoxication: Euphoria, grandiosity, mydriasis, prolonged wakefulness, hyperalertness, hypertension, paranoia, fever, skin excoriations (meth), severe: cardiac arrest, seizures
• Treatment: Benzodiazepines (for agitation and seizures)
• Withdrawal: "Meth mites"

Methamphetamine

• MOA: Enhances release of monoamines (5HT, NE, DA)
• Intoxication: Pupil dilation, agitation, euphoria, tactile hallucinations, alertness, arousal, wakefulness
• Withdrawal: Sleepiness, hunger, depression

Caffeine

• MOA: Adenosine receptor antagonist
• Intoxication: Palpitations, agitation, tremors, insomnia
• Withdrawal: Headache, difficulty concentrating, flu-like symptoms

Cocaine

• MOA: Blocks reuptake of monoamines (5HT, NE, DA) or blocks dopamine (DAT), serotonin (SERT), norepinephrine (NET) transporters
• Intoxication: Impaired judgment, pupillary dilation, diaphoresis, hallucinations, paranoia, angina, sudden cardiac death
• Treatment: Benzodiazepines (diazepam), phentolamine for cardiovascular management, nitroglycerin for refractory hypertension or non-selective beta-blockers
• Withdrawal: Restlessness, hunger, severe depression, sleep disturbance

Nicotine

• MOA: Stimulates central nicotinic acetylcholine receptors
• Intoxication: Restlessness
• Withdrawal: Irritability, anxiety, restlessness, decreased concentration, increased appetite/weight
• Treatment: Nicotine replacement therapy (patch, gum, lozenge), bupropion, varenicline

Hallucinogens (LSD)

• MOA: 5-HT2A receptor agonist (increases serotonin activity)
• Intoxication: Perceptual distortion (visual, auditory), depersonalization, anxiety, paranoia, psychosis, flashbacks
• Withdrawal: None

MDMA (Ecstasy)

• MOA: Blocks reuptake of 5HT and DA, or induces reversal of transporters for monoamines (SERT > DAT, NET), increasing neurotransmitter release.
• Intoxication: Euphoria, hallucinations, disinhibition, hyperactivity, thirst increase, bruxism, distorted sensory and time perception, mydriasis (pupil dilation)
• Withdrawal: Depression, fatigue, change in appetite, difficulty concentrating, anxiety

Phencyclidine (PCP)

• MOA: NMDA receptor antagonist
• Intoxication: Violence, nystagmus, impulsivity, psychomotor agitation, tachycardia, hypertension, analgesia, psychosis, delirium, seizures
• Withdrawal: Recurrence of intoxication symptoms (GI tract reabsorption), sudden onset of severe violence.

Dependence vs. Addiction

• Dependence: Body's adaptation to a drug; reaction when drug is stopped
• Addiction: Loss of control and compulsive drug use; includes psychological cravings.