Substance use disorders

Following are the 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 like tremulousness, tachycardia, diaphoresis, nausea, anxiety, and irritability occur within a few hours of stopping or decreasing the dose of alcohol. They are managed 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. Treatment is with diazepam/lorazepam/chlordiazepoxide, antipsychotics like 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 (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 and with sedatives like diazepam or haloperidol to control aggressive thought and behavior.
Inhalants: They include paint thinners, spray paints, gasoline, glue and solvents which 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 and 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 drugs. 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 presents within a few hours to days of stopping the opioid drug and lasts for up to 2 weeks. It presents with 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 (less potent opioid agonist) or buprenorphine (a partial opioid agonist), can be used to prevent withdrawal symptoms and they are gradually tapered off over a few months typically. Naltrexone is a long acting narcotic antagonist used as a maintenance therapy of opioid de-addiction programs. Methylnaltrexone is a peripherally acting opioid antagonist that is 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, Light reflex is sluggish. Benzodiazepines alone do not cause death, unless they are combined with other CNS depressants like alcohol, barbiturates etc. Management includes gastric lavage, induction of emesis if presenting within 30 minutes and 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, that manifests as REM rebound, nightmares, anxiety, restlessness, tremulousness, diaphoresis, delirium, seizures and cardiovascular collapse. It is treated with pento/phenobarbital is used to control symptoms and 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 and haloperidol etc.
- Cocaine dependence is treated with bupropion, venlafaxine, amantadine and cognitive therapy.
Other drugs: Drugs like Ecstasy or MDMA (amphetamine derivative), 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 like atropine and belladonna alkaloids may cause accidental or intentional toxicity. Similar syndrome may be seen in elderly or in overdose of TCAs, paroxetine, thioridazine, scopolamine and 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 and supportive therapy.

Substance use disorders

Following are the 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 like tremulousness, tachycardia, diaphoresis, nausea, anxiety, and irritability occur within a few hours of stopping or decreasing the dose of alcohol. They are managed 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. Treatment is with diazepam/lorazepam/chlordiazepoxide, antipsychotics like 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 (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 and with sedatives like diazepam or haloperidol to control aggressive thought and behavior.
Inhalants: They include paint thinners, spray paints, gasoline, glue and solvents which 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 and 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 drugs. 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 presents within a few hours to days of stopping the opioid drug and lasts for up to 2 weeks. It presents with 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 (less potent opioid agonist) or buprenorphine (a partial opioid agonist), can be used to prevent withdrawal symptoms and they are gradually tapered off over a few months typically. Naltrexone is a long acting narcotic antagonist used as a maintenance therapy of opioid de-addiction programs. Methylnaltrexone is a peripherally acting opioid antagonist that is 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, Light reflex is sluggish. Benzodiazepines alone do not cause death, unless they are combined with other CNS depressants like alcohol, barbiturates etc. Management includes gastric lavage, induction of emesis if presenting within 30 minutes and 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, that manifests as REM rebound, nightmares, anxiety, restlessness, tremulousness, diaphoresis, delirium, seizures and cardiovascular collapse. It is treated with pento/phenobarbital is used to control symptoms and 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 and haloperidol etc.
- Cocaine dependence is treated with bupropion, venlafaxine, amantadine and cognitive therapy.
Other drugs: Drugs like Ecstasy or MDMA (amphetamine derivative), 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 like atropine and belladonna alkaloids may cause accidental or intentional toxicity. Similar syndrome may be seen in elderly or in overdose of TCAs, paroxetine, thioridazine, scopolamine and 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 and supportive therapy.