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