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 login to view 1 more bullet 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 login to view 3 more bullets suboxone login to view 4 more bullets Barbiturates intoxication respiratory/CNS depression does not have a depression "ceiling" treatment of intoxication must treat withdrawal with barbiturates not benzodiazepines symptom management login to view 2 more bullets withdrawal anxiety, seizures, delirium login to view 1 more bullet 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 login to view 1 more bullet sympathetic activation, login to view 1 more bullet withdrawal depression, lethargy, headache, stomach cramps, hunger, hypersomnolence MDMA ("ecstacy") mechanism similar to amphetamines effects 5-HT more than dopamine login to view 1 more bullet intoxication hyperthermia and social closeness login to view 1 more bullet withdrawal mood offset for several weeks Cocaine mechanism block biogenic amine (DA, NE, 5HT) reuptake intoxication mental status changes login to view 1 more bullet sympathetic activation login to view 1 more bullet stereotyped behavior login to view 1 more bullet 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 login to view 1 more bullet amotivational syndrome withdrawal mild symptoms login to view 1 more bullet 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