Substance use disorders

Following are commonly abused substances and their toxicities, withdrawal symptoms, and management.

Alcohol: Signs of alcohol intoxication include slurred speech, loss of coordination, unsteady gait, nystagmus, restlessness, dilated pupils, impaired memory, and stupor/coma. Intracranial pressure may be elevated. Treatment is symptomatic; hemodialysis may be needed in severe cases.
- Withdrawal symptoms such as tremulousness, tachycardia, diaphoresis, nausea, anxiety, and irritability occur within a few hours of stopping or decreasing alcohol intake. Manage with thiamine and diazepam or chlordiazepoxide.
- Delirium tremens is a life-threatening withdrawal syndrome that occurs 2-3 days after stopping or decreasing alcohol intake in chronic heavy drinkers. It presents with delirium, tremulousness, hallucinations, tachycardia, hypertension, sweating, and agitation. Treat with diazepam/lorazepam/chlordiazepoxide; antipsychotics such as haloperidol or risperidone as needed; thiamine; valproic acid as an adjunct to diazepam; and supportive therapy in the ICU.
Tobacco/nicotine: Nicotine is one of the most addictive substances known. Withdrawal presents with malaise, anxiety, cravings, and irritability. Nicotine patches, clonidine, bupropion, and varenicline (a partial agonist at the nicotine receptor) are used to manage withdrawal symptoms. Varenicline increases the risk of depression and suicide.
Cannabis: This class includes marijuana, hashish, and tetrahydrocannabinol (THC). Intoxication presents as euphoria, increased appetite, dry mouth, red conjunctiva, tachycardia, anxiety, and rarely hallucinations. Pupils may be normal or dilated. Treatment is symptomatic; diazepam can be used.
Hallucinogens: They include LSD, PCP or phencyclidine (angel dust), mescaline, and psilocybin (from some types of mushrooms). Intoxication presents with dilated pupils, tachycardia, hypertension, fever, illusions, hallucinations, depersonalization, and anxiety. PCP is associated with violent behavior, hyperacusis, analgesia, muscle rigidity, nystagmus, and seizures. Treatment is symptomatic, with sedatives such as diazepam or haloperidol to control aggressive thought and behavior.
Inhalants: They include paint thinners, spray paints, gasoline, glue, and solvents that are sniffed. Chronic use causes permanent brain damage and dementia. Acute intoxication presents with dizziness, euphoria, confusion, nystagmus, ataxia, dysarthria, tremors, delirium, and blurred vision. There is no antidote; treatment is symptomatic.
Opioids, heroin and related prescription drugs: This class includes morphine, heroin, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone, meperidine, methadone, and propoxyphene. Many agents are used as narcotic pain medications and are highly addictive. Intoxication presents with analgesia, mental clouding, euphoria, nausea, vomiting, flushed warm skin, constricted pupils, apathy, lethargy, constipation, illusions, etc. Life-threatening severe toxicity presents with miosis, respiratory depression, hypotension, pulmonary edema, seizures, coma, and death.

Treatment of opioid intoxication:
- ABCs, naloxone (should respond to up to 3 doses)
- Naloxone is a competitive inhibitor at mu opioid receptor
- Caution as naloxone may precipitate acute opioid withdrawal presenting as agitation, delirium etc.
- Recurrence of respiratory depression may occur, so admit for observation, repeat naloxone if needed

Opioid withdrawal is not life threatening. It begins within a few hours to days of stopping the opioid drug and can last up to 2 weeks. Symptoms include lacrimation, sweating, rhinorrhea, restlessness, dilated pupils, insomnia, cravings, and gooseflesh. Opioid withdrawal can be managed in an outpatient setting. Clonidine can be used to decrease symptoms. Methadone (a less potent opioid agonist) or buprenorphine (a partial opioid agonist) can be used to prevent withdrawal symptoms; these are typically tapered gradually over a few months. Naltrexone is a long-acting narcotic antagonist used as maintenance therapy in opioid de-addiction programs. Methylnaltrexone is a peripherally acting opioid antagonist used to treat opioid-induced constipation and paralytic ileus.

Sedatives, hypnotics, including benzodiazepines and barbiturates: Intoxication presents as sedation, paradoxical excitement in elderly and children, nystagmus, dysarthria, memory lapses and inattention, hypotension, respiratory depression, depressed reflexes, hypoxia, hypothermia, stupor, coma, and death. Pupils may be normal, dilated, or constricted; the light reflex is sluggish. Benzodiazepines alone do not cause death unless combined with other CNS depressants such as alcohol, barbiturates, etc. Management includes gastric lavage, induction of emesis if presenting within 30 minutes and the gag reflex is intact, airway protection, oxygen, diuresis, urinary alkalinization to increase excretion, hemodialysis, and symptomatic treatment.
- Abruptly stopping benzodiazepines and barbiturates precipitates a life-threatening withdrawal syndrome within 12-24 hours of stopping the drug. It manifests as REM rebound, nightmares, anxiety, restlessness, tremulousness, diaphoresis, delirium, seizures, and cardiovascular collapse. It is treated with pento/phenobarbital to control symptoms, and the medication needs to be tapered gradually. Supportive therapy is also needed.
Stimulants: They include cocaine, crack or smokable cocaine, methamphetamine (speed), methylphenidate, phenylpropanolamine, and pemoline sodium. Some stimulants are used in the treatment of ADHD. Intoxication presents with elevated mood, increased alertness and energy, decreased appetite, anxiety, irritability, hypertension, tachycardia, agitation, full-blown psychosis, anger, hallucinations, delusions, dilated pupils, arrhythmias, seizures, ICH, multiple mini-infarcts in the brain, coma, and death. Treatment is symptomatic, with control of vitals, phentolamine, haloperidol, etc.
- Cocaine dependence is treated with bupropion, venlafaxine, amantadine, and cognitive therapy.
Other drugs: Drugs such as Ecstasy or MDMA (an amphetamine derivative) and ketamine or special K are drugs of abuse. Intoxication presents with euphoria, increased sexuality, amnesia, disinhibition, hypertension, tachycardia, hyperthermia, bruxism, and rarely renal or hepatic failure. Treatment is supportive; alprazolam may be used.
- Anticholinergics such as atropine and belladonna alkaloids may cause accidental or intentional toxicity. A similar syndrome may be seen in elderly patients or in overdose of TCAs, paroxetine, thioridazine, scopolamine, and a few over-the-counter sleep and cold medications. Symptoms include irritability, tachycardia, dilated pupils, fever, amnesia, delirium, hallucinations, warm and dry skin, and coma. Treatment is with physostigmine and donepezil, plus supportive therapy.

Following are commonly abused substances and their toxicities, withdrawal symptoms, and management.

Alcohol: Signs of alcohol intoxication include slurred speech, loss of coordination, unsteady gait, nystagmus, restlessness, dilated pupils, impaired memory, and stupor/coma. Intracranial pressure may be elevated. Treatment is symptomatic; hemodialysis may be needed in severe cases.
- Withdrawal symptoms such as tremulousness, tachycardia, diaphoresis, nausea, anxiety, and irritability occur within a few hours of stopping or decreasing alcohol intake. Manage with thiamine and diazepam or chlordiazepoxide.
- Delirium tremens is a life-threatening withdrawal syndrome that occurs 2-3 days after stopping or decreasing alcohol intake in chronic heavy drinkers. It presents with delirium, tremulousness, hallucinations, tachycardia, hypertension, sweating, and agitation. Treat with diazepam/lorazepam/chlordiazepoxide; antipsychotics such as haloperidol or risperidone as needed; thiamine; valproic acid as an adjunct to diazepam; and supportive therapy in the ICU.
Tobacco/nicotine: Nicotine is one of the most addictive substances known. Withdrawal presents with malaise, anxiety, cravings, and irritability. Nicotine patches, clonidine, bupropion, and varenicline (a partial agonist at the nicotine receptor) are used to manage withdrawal symptoms. Varenicline increases the risk of depression and suicide.
Cannabis: This class includes marijuana, hashish, and tetrahydrocannabinol (THC). Intoxication presents as euphoria, increased appetite, dry mouth, red conjunctiva, tachycardia, anxiety, and rarely hallucinations. Pupils may be normal or dilated. Treatment is symptomatic; diazepam can be used.
Hallucinogens: They include LSD, PCP or phencyclidine (angel dust), mescaline, and psilocybin (from some types of mushrooms). Intoxication presents with dilated pupils, tachycardia, hypertension, fever, illusions, hallucinations, depersonalization, and anxiety. PCP is associated with violent behavior, hyperacusis, analgesia, muscle rigidity, nystagmus, and seizures. Treatment is symptomatic, with sedatives such as diazepam or haloperidol to control aggressive thought and behavior.
Inhalants: They include paint thinners, spray paints, gasoline, glue, and solvents that are sniffed. Chronic use causes permanent brain damage and dementia. Acute intoxication presents with dizziness, euphoria, confusion, nystagmus, ataxia, dysarthria, tremors, delirium, and blurred vision. There is no antidote; treatment is symptomatic.
Opioids, heroin and related prescription drugs: This class includes morphine, heroin, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone, meperidine, methadone, and propoxyphene. Many agents are used as narcotic pain medications and are highly addictive. Intoxication presents with analgesia, mental clouding, euphoria, nausea, vomiting, flushed warm skin, constricted pupils, apathy, lethargy, constipation, illusions, etc. Life-threatening severe toxicity presents with miosis, respiratory depression, hypotension, pulmonary edema, seizures, coma, and death.

Treatment of opioid intoxication:
- ABCs, naloxone (should respond to up to 3 doses)
- Naloxone is a competitive inhibitor at mu opioid receptor
- Caution as naloxone may precipitate acute opioid withdrawal presenting as agitation, delirium etc.
- Recurrence of respiratory depression may occur, so admit for observation, repeat naloxone if needed

Opioid withdrawal is not life threatening. It begins within a few hours to days of stopping the opioid drug and can last up to 2 weeks. Symptoms include lacrimation, sweating, rhinorrhea, restlessness, dilated pupils, insomnia, cravings, and gooseflesh. Opioid withdrawal can be managed in an outpatient setting. Clonidine can be used to decrease symptoms. Methadone (a less potent opioid agonist) or buprenorphine (a partial opioid agonist) can be used to prevent withdrawal symptoms; these are typically tapered gradually over a few months. Naltrexone is a long-acting narcotic antagonist used as maintenance therapy in opioid de-addiction programs. Methylnaltrexone is a peripherally acting opioid antagonist used to treat opioid-induced constipation and paralytic ileus.

Sedatives, hypnotics, including benzodiazepines and barbiturates: Intoxication presents as sedation, paradoxical excitement in elderly and children, nystagmus, dysarthria, memory lapses and inattention, hypotension, respiratory depression, depressed reflexes, hypoxia, hypothermia, stupor, coma, and death. Pupils may be normal, dilated, or constricted; the light reflex is sluggish. Benzodiazepines alone do not cause death unless combined with other CNS depressants such as alcohol, barbiturates, etc. Management includes gastric lavage, induction of emesis if presenting within 30 minutes and the gag reflex is intact, airway protection, oxygen, diuresis, urinary alkalinization to increase excretion, hemodialysis, and symptomatic treatment.
- Abruptly stopping benzodiazepines and barbiturates precipitates a life-threatening withdrawal syndrome within 12-24 hours of stopping the drug. It manifests as REM rebound, nightmares, anxiety, restlessness, tremulousness, diaphoresis, delirium, seizures, and cardiovascular collapse. It is treated with pento/phenobarbital to control symptoms, and the medication needs to be tapered gradually. Supportive therapy is also needed.
Stimulants: They include cocaine, crack or smokable cocaine, methamphetamine (speed), methylphenidate, phenylpropanolamine, and pemoline sodium. Some stimulants are used in the treatment of ADHD. Intoxication presents with elevated mood, increased alertness and energy, decreased appetite, anxiety, irritability, hypertension, tachycardia, agitation, full-blown psychosis, anger, hallucinations, delusions, dilated pupils, arrhythmias, seizures, ICH, multiple mini-infarcts in the brain, coma, and death. Treatment is symptomatic, with control of vitals, phentolamine, haloperidol, etc.
- Cocaine dependence is treated with bupropion, venlafaxine, amantadine, and cognitive therapy.
Other drugs: Drugs such as Ecstasy or MDMA (an amphetamine derivative) and ketamine or special K are drugs of abuse. Intoxication presents with euphoria, increased sexuality, amnesia, disinhibition, hypertension, tachycardia, hyperthermia, bruxism, and rarely renal or hepatic failure. Treatment is supportive; alprazolam may be used.
- Anticholinergics such as atropine and belladonna alkaloids may cause accidental or intentional toxicity. A similar syndrome may be seen in elderly patients or in overdose of TCAs, paroxetine, thioridazine, scopolamine, and a few over-the-counter sleep and cold medications. Symptoms include irritability, tachycardia, dilated pupils, fever, amnesia, delirium, hallucinations, warm and dry skin, and coma. Treatment is with physostigmine and donepezil, plus supportive therapy.