INTRODUCTION General most addictive drugs act on the dopamine mesolimbic-reward pathway withdrawal symptoms are often the opposite of intoxication e.g., mydraisis and miosis - opioid intoxication depressant withdrawal generally more life-threatening than stimulant withdrawal substance use typically denied or underreported check urine drug immunoassay to screen for substance use if urine drug test is positive, will need follow-up gas chromatography / mass spectrometry assessment to confirm and quantiy drug use collect collateral info from friends/family Drug classes depressants opioids (mu agonist) barbiturates (GABAa channel opening duration increased) benzodiazepines (GABAa channel opening frequency increased) alcohol stimulants amphetamine MDMA cocaine caffeine nicotine hallucinogens PCP LSD marijuana General complications injection drug users at risk for right-sided endocarditis hepatitis and abscesses overdose hemorrhoids AIDS Snapshot A young male is brought into the ED by his friends who say he is not responding to them. The patient seems extremely drowsy and has slurred speech. On physical exam he has pinpoint pupils and his respiratory rate is 4/min. Opioids Mechanism mu receptor agonist Examples morphine, heroin, methadone Intoxication presentation constipation - no tolerance to this side effect respiratory depression - life threatening, specific pupillary constriction (pinpoint pupils) seizures (overdose is life-threatening) for heroin use, look for track marks (needle injections) treatment pharmacologic naloxone opioid receptor antagonist opioid withdrawal is NOT fatal - it is just unpleasant can cause pulmonary edema symptomatic treatment and observation indicated for patients who are adequately protecting the airway with no concerns for hypoxia or hypercapnia Withdrawal presentation anxiety, insomnia, anorexia, sweating, dilated pupils, piloerection ("cold turkey"), fever, rhinorrhea, nausea, stomach cramps, diarrhea ("flulike" symptoms) yawning unpleasant but not life-threatening treatment of withdrawal clonidine α2 agonist that decreases NE and sympathetic output making autonomic symptoms less intense overdose presents with somnolence, miosis, and bradycardia methadone (long-acting) buprenorphine + naloxone can precipitate withdrawal if given too soon (partial mu agonist) treatment of addiction pharmacologic methadone typically oral long-acting IV opiate used for heroin detoxification or long-term maintenance suboxone (buprenorphine + naloxone) 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 when suboxone is injected naltrexone opioid antagonist used to assist in blocking cravings for both opioids (and alcohol) should not be used for opioid overdose as it takes longer to take effect as compared to naloxone Snapshot A patient presents to the ED with impaired memory, poor concentration and extreme drowsiness. Pupils are not dilated on exam and the patient is minimally responsive. Of greatest concern is the patient's respiratory rate of 5/min. Barbiturates Mechanism GABAa channel - increased duration of opening Intoxication presentation respiratory/CNS depression - can be fatal does not have a depression "ceiling" in contrast to benzodiazepines treatment pharmacologic symptom management support BP non-pharmacologic assist respiration intubate if necessary Withdrawal presentation anxiety, seizures, delirium similar to alcohol life-threatening cardiovascular collapse additive affects with alcohol treatment pharmacologic long-acting benzodiazepines with taper could also use long-acting barbiturates (phenobarbital) Snapshot A patient with a past medical history of panic attacks and anxiety is brought into the ED by her husband as she has been stuporous and has been minimally responsive and extremely drowsy. The patient's husband mentions that his wife did have a panic attack today. Benzodiazepines Mechanism GABAa channel - increased frequency of opening Intoxication presentation amnesia, ataxia, stupor/somnolence, minor respiratory depression has a depression "ceiling" additive affects with alcohol treatment pharmacologic flumazenil competitive GABAa antagonist DO NOT treat benzodiazepine overdose with flumazenil in general it is benign and the patient can "sleep off" the overdose offer respiratory support if needed flumazenil can precipitate seizures particularly if the patient is benzodiazepine dependent Withdrawal presentation rebound anxiety seizures (life-threatening) and tremor most commonly from short-acting benzos (e.g. alprazolam) insomnia treatment pharmacologic long-acting benzodiazepine to taper off dose e.g., clonazepam, diazepam symptomatic treatment Snapshot A 25-year-old male is brought into the ED by his own volition as he has been unable to sleep for the past 5 nights and is concerned. He says he feels as if he doesn't need to sleep but came in at the request of his friend. He has been studying all night for finals and says he has been, "in the zone," and been unable to stay up all night with no need for sleep. Amphetamines Mechanism simulates biogenic amine (DA, NE, 5HT) release + decreases reuptake (high dose) Intoxication presentation mental status changes euphoria, impaired judgment, delusions, hallucinations, prolonged wakefulness/attention sympathetic activation psychomotor agitation, pupillary dilation, hypertension, tachycardia, fever, cardiac arrhythmias treatment pharmacologic antipsychotics (haloperidol) benzodiazepines vitamin C (promotes excretion) antihypertensives propranolol (BP + tachycardia control) non-pharmacologic do not restrain patients may result in rhabdomyolysis Snapshot A 23-year-old female is brought into the ED by her friends as they are concerned about her behavior. She seems more energetic than usual and this has gone on well past the end of the rave. On exam, you see a young female in neon clothing, consumed with the colors of her outfit, and very affectionate towards you. MDMA (Ecstasy) Mechanism similar to amphetamines effects 5-HT more than dopamine may damage serotonergic neurons Intoxication presentation hyperthermia and social closeness "club drug" hyponatremia due to increased fluid intake or antidiuretic hormone (ADH) secretion treatment no specific treatment symptomatic treatment only Withdrawal presentation mood offset for several weeks treatment no specific treatment symptomatic treatment only Snapshot A 21-year-old male is brought into the ED by the police for an altercation. Last night, the patient was at a party and seemed much more active than usual according to his girlfriend. He punched another male at the party in the face claiming that he was hitting on his girlfriend. On exam, you see an agitated young male with dilated pupils, and his pulse is 128/min. Cocaine Mechanism block biogenic amine (DA, NE, 5HT) reuptake Intoxication presentation mental status changes euphoria, psychomotor agitation, grandiosity, hallucinations (including tactile), paranoid ideations sympathetic activation ↓ appetite, tachycardia, pupillary dilation, hypertension, angina, warm/sweaty skin can cause severe vasospasm MI - coronary vasospasm beta-blockers contraindicated in MI secondary to cocaine cocaine increases the release of catecholamines and beta-blockade leads to unopposed alpha-agonism may cause hypertensive crisis placental infarction - vasospasm of placental vessels nasal septum perforation - Kiesselbach's plexus vasospasm stroke - CVA stereotyped behavior repetitive motions (eg. digging through trash) treatment pharmacologic antipsychotics (haloperidol) benzodiazepines antihypertensives (labetalol - need alpha-1 blockade) vitamin C - promotes excretion non-pharmacologic do not restrain patients may result in rhabdomyolysis Withdrawal presentation severe depression and suicidality hyperphagia, hypersomnolence, fatigue, malaise severe psychological craving treatment pharmacologic bupropion bromocriptine SSRI's for depression Chronic/long-term treatment individual and group psychotherapy Snapshot A 22-year-old college student has been studying for finals but came into the emergency department because of a strange sensation in her chest and a feeling of palpitations. She has been studying every night consuming copious amounts of energy drinks and is unsure what is going on but is afraid that she is, "having a heart attack from all the stress." A segment of the girl's EKG is pointed out to you by the on call cardiologist. Caffeine Mechanism adenosine antagonist → decreased GABA activity (wakefulness) Intoxication presentation restlessness, insomnia diuresis muscle twitching cardiac arrhythmias treatment no specific treatment symptomatic treatment only Withdrawal presentation headache, lethargy, depression, weight gain treatment no specific treatment symptomatic treatment only Snapshot A patient comes to his primary care physician because he has felt more anxious and irritable lately. He states that he has been very stressed out at work lately and thinks that his symptoms are attributable to the stress. He smokes 1 pack per day, but lately has found himself smoking up to 4 packs per day to ease his stress. Upon further counseling he says he is interested in quitting and wants your help. Nicotine Intoxication presentation restlessness, insomnia, anxiety, arrhythmias treatment no specific treatment symptomatic treatment only Withdrawal presentation irritability, headache, anxiety, weight gain, craving treatment for cessation pharmacologic bupropion can lower seizure threshhold (for exam purposes) varenicline partial nicotine receptor agonism mediates partial reward of nicotine yet blocks reward of nicotine highest success rate of other anti-smoking drugs, particularly when stacked with nicotine patches nicotine administration via other routes bromocriptine Snapshot A young man is brought into the ED and has attempted to assault a nurse several times. He is extremely aggressive and becomes enraged when sudden movements or loud sounds are made. The patient is escorted to a dimly lit, quiet exam room where he becomes much calmer. On physical exam, the patient is agitated and has nystagmus. His blood pressure in the ED is 180/100 mmHg. PCP Mechanism NMDA receptor antagonist ketamine is a similar drug Intoxication presentation belligerence, impulsiveness, fear, homicidality, psychosis, delirium, seizures, psychomotor agitation, vertical and horizontal nystagmus, tachycardia, ataxia treatment pharmacologic benzodiazepines antipsychotics (haloperidol) if benzodiazepines are not adequately sedating patient further management low stimulus environment restraints if needed to prevent patient from hurting self/others Withdrawal presentation depression, anxiety, irritability, restlessness, anergia, disturbances of thought and sleep treatment no specific treatment symptomatic treatment only Snapshot A 23-year-old male is brought into the ED by his friends at 1 a.m. They are afraid that he is going to hurt himself. They say that he has "been freaking out" and seeing things that are not there. At one point, he tried to ride a bike off the roof of a house. On exam, you see a young man who appears to be in a panic. His gait is abnormal, he has diffuse tremors and his pupils are dilated. LSD Mechanism action at 5-HT receptor Intoxication presentation visual hallucinations and synesthesias (e.g., seeing sound as color) marked anxiety or depression, delusions, pupillary dilation "bad trip" panic treatment pharmacologic antipsychotics (e.g., haloperidol) benzodiazepines talking down, supportive counseling Withdrawal presentation largely no withdrawal because it does not effect dopamine flashbacks can occur years later treatment no specific treatment symptomatic treatment only Snapshot A 17-year-old male is brought to his family physician by his parents due to his behavior - increased appeptite, lack of motivation, and paranoia. When interviewing the patient, the physician notes a slowed speech and conjunctival injection. Marijuana (Cannabis) Mechanism binds to CB1/CB2 cannabinoid receptors Intoxication presentation euphoria, anxiety, disinhibition, paranoid delusions, perception of slowed time, conjunctival injection, impaired judgment, social withdrawal, ↑ appetite, dry mouth, hallucinations largely psychological effects amotivational syndrome hyperemesis syndrome treatment no specific treatment symptomatic treatment only Withdrawal presentation 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 treatment no specific treatment symptomatic treatment only Snapshot A 15-year-old male is brought to the ED for aggressive behavior. This patient has been admitted to the ED many times, last time for abusing bath salts. He comes from a foster home and is largely unsupervised. Inhalants Mechanism unknown Intoxication presentation belligerence, assaultiveness apathy, impaired judgement blurred vision, coma treatment no specific treatment antipsychotics (haloperidol) if severe aggression Withdrawal not well characterized, no treatment abuse of other drugs commonly seen in these patients often from a low socioeconomic background Snapshot A 69-year-old male presents to the emergency department with sudden, severe onset epigastric pain that began while he was watching television. On physical exam is an unkempt male with pain upon palpation of the epigastric region. Labs are drawn and the patient has an elevated amylase and lipase. The patient is made NPO, an NG tube is placed, and the patient is given IV fluids. The patient is noted to be experiencing hallucinations. On his second hospital day, the patient has a seizure. Alcohol Minor WithdrawalAlcoholic HallucinosisWithdrawal SeizureDelirium TremensTime Since Last Drink6 hours12 - 24 hours48 hours48 - 96 hoursSymptomsTremblingIrritabilityAnxietyHeadacheTachycardiaInsomniaVisual, auditory, and in some cases tactile hallucinationsTonic-clonic seizuresAutonomic instabilityDisorientationHallucinationsAgitationManagementThiamineFolateMultivitaminDextroseIV FluidsBenzodiazepineslorazepamdiazepam - longer half lifemidazolam drip though not a preferred initial agentBarbituratessimple single dose that auto-taperspreferred in very ill or highly symptomatic patients to reduce ICU admissionsBenzodiazepine taperHead CTSuspect in patient with unknown history follwed by DT symptoms 2 days laterBenzodiazepine taper Mechanism (seizure) alcohol is a depressant - increases GABAa channel opening long term use leads to downregulation of GABA channels (inhibitory) and upregulation of NMDA (excitatory) Intoxication presentation wide and varied - talkative, flirtatious, aggressive, moody, disinhibited treatment secure airway thiamine, magnesium, multivitamin, dextrose (particularly if chronic alcoholism) benzodiazepines (if withdrawal) addiction medications disulfiram - inhibits acetaldehyde dehydrogenase, aversive conditioning naltrexone - decreases desire gabapentin - decreases desire