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General Concepts
  • ALL addictive drugs act on the dopamine mesolimbic-reward pathway
  • Withdrawal symptoms are often the opposite of intoxication
    • e.g. miosis in opioid intoxication and mydriasis in withdrawal 
  • Depressant withdrawal is generally more life-threatening than stimulant withdrawal
  • Injection drug users at risk for
    • right-sided endocarditis
    • hepatitis and abscesses
    • overdose
    • hemorrhoids
    • AIDS
Depressants
  • Opioids (e.g. morphine, heroin, methadone)
    • intoxication 
      • nausea and vomiting with constipation
      • respiratory depression 
      • pupillary constriction (pinpoint pupils = miosis)
      • seizures (overdose is life-threatening)
      • for heroin use look for track marks (needle injections)
    • treatment for intoxication
      • naloxone/naltrexone
        • opioid receptor antagonist
      • symptomatic treatment
    • withdrawal
      • anxiety, insomnia, anorexia, sweating, dilated pupils, piloerection ("cold turkey"), fever, rhinorrhea, nausea, stomach cramps, diarrhea ("flulike" symptoms), muscle jerks, yawning
      • unpleasant but not life-threatening
    • treatment for withdrawal (examples mainly for heroin)
      • methadone
        • long-acting IV opiate
        • used for heroin detoxification or long-term maintenance
        • safe and used in pregnancy
      • suboxone
        • long acting oral administration with fewer withdrawal symptoms than methadone
        • naloxone + buprenorphine (partial opioid agonist)
        • naloxone is not active when taken orally, so withdrawal symptoms occur only if injected
          • intended to prevent overdose/enjoyment when suboxone is injected
  • Barbiturates
    • intoxication
      • respiratory/CNS depression
      • does not have a depression "ceiling"
    • treatment of intoxication
      • must treat withdrawal with barbiturates not benzodiazepines
      • symptom management
        • assist respiration
        • ↑ BP
    • withdrawal 
      • anxiety, seizures, delirium
        • similar to alcohol
      • life-threatening cardiovascular collapse
      • additive affects with alcohol
  • Benzodiazepines
    • intoxication
      • amnesia, ataxia, stupor/somnolence, minor respiratory depression
      • has a depression "ceiling"
      • additive affects with alcohol
      • treat with flumazenil (competitive GABA antagonist)
    • treatment for intoxication
      • flumazenil (competitive GABA antagonist) 
    • withdrawal
      • rebound anxiety
      • seizures (life-threatening), tremor
      • insomnia
    • treatment for withdrawal
      • long acting benzodiazepine (e.g. diazepam) to taper off dose
      • symptomatic treatment
  • Alcohol
    • see Alcohol topic
Stimulants
  • Amphetamines
    • mechanism
      • simulates biogenic amine (DA, NE, 5HT) release
    • intoxication
      • mental status changes
        • euphoria, impaired judgment, delusions, hallucinations, prolonged wakefulness/attention
      • sympathetic activation,
        • psychomotor agitation, pupillary dilation, hypertension, tachycardia, fever, cardiac arrhythmias
    • withdrawal
      • depression, lethargy, headache, stomach cramps, hunger, hypersomnolence
  • MDMA ("ecstacy")
    • mechanism
      • similar to amphetamines
      • effects 5-HT more than dopamine
        • may damage serotonergic neurons
    • intoxication
      • hyperthermia and social closeness
        • club drug
    • withdrawal
      • mood offset for several weeks
  • Cocaine
    • mechanism
      • block biogenic amine (DA, NE, 5HT) reuptake
    • intoxication
      • mental status changes
        • euphoria, psychomotor agitation, grandiosity, hallucinations (including tactile), paranoid ideations
      • sympathetic activation
        • ↓ appetite, tachycardia, pupillary dilation, hypertension, angina, sudden cardiac death, stroke (intense vasoconstriction)
      • stereotyped behavior
        • repetitive motions (e.g. digging through trash)
    • treatment for intoxication
      • benzodiazepines
      • neuroleptics
      • reduce blood pressure and body temperature
    • withdrawal
      • severe depression and suicidality, hyperphagia, hypersomnolence, fatigue, malaise, severe psychological craving
  • Caffeine
    • intoxication
      • restlessness and insomnia
      • ↑ diuresis
      • muscle twitching
      • cardiac arrhythmias
    • withdrawal
      • headache, lethargy, depression, weight gain
  • Nicotine
    • intoxication
      • restlessness, insomnia, anxiety, arrhythmias
    • withdrawal
      • irritability, headache, anxiety, weight gain, craving
    • treatment for cessation
      • bupropion (NE and dopamine reuptake inhibitor)
      • varenicline (partial nicotinic receptor agonist)
      • nicotine administration via other routes (patch, gum, lozenges)
Hallucinogens
  • PCP
    • intoxication
      • belligerence, impulsiveness, fear, homicidality, psychosis, delirium, seizures, psychomotor agitation, vertical and horizontal nystagmus, tachycardia, ataxia 
    • withdrawal
      • depression, anxiety, irritability, restlessness, anergia, disturbances of thought and sleep
    • note: ketamine is a similar drug; both are NMDA antagonists 
  • LSD
    • mechanism
      • action at 5-HT receptor
    • intoxication
      • visual hallucinations and synesthesias (e.g. seeing sound as color)
      • marked anxiety or depression, delusions, pupillary dilation
      • bad trip panic
    • withdrawal
      • largely no withdrawal because it does not effect dopamine
      • flashbacks years later
  • Marijuana
    • mechanism
      • binds to CB1/CB2 cannabinoid receptors
    • intoxication
      • euphoria, anxiety, disinhibition, paranoid delusions, perception of slowed time, impaired judgment, social withdrawal, ↑ appetite, dry mouth, hallucinations
        • largely psychological effects
      • amotivational syndrome
    • withdrawal
      • mild symptoms
        • irritability, depression, insomnia, nausea, anorexia
      • most symptoms peak in 48 hours and last for 5-7 days
      • can be detected in urine up to 1 month after last use
    • note: dronabinol is a cannabinoid used as an antiemetic
 

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