Substance Use Disorder

In 2018, what percentage of Americans 12 years of age or older reported current substance use in the past month?

60.2% (164.8 million)

In 2018, what percentage of Americans 12 years of age or older reported current alcohol use?

51.1% (139.8 million)

What are the behavioral signs & symptoms of alcohol intoxication?

• Disinhibition

• euphoria

• dysphoria

• inappropriate aggressive or sexual behavior

• impaired judgment; possibly progressing to somnolence and coma as the blood level increases

What are the psychological signs & symptoms of alcohol intoxication?

• Blood levels 0.02%–0.1% (20–100 mg/dL or 4.3–21.7 mmol/L): Slight impairment (eg, reaction time)

• Blood levels 0.1%–0.2% (100–200 mg/dL or 21.7–43.4 mmol/L): Significant impairment (eg, balance, speech, vision)

• Blood levels 0.2%–0.3% (200–300 mg/dL or 43.4–65.1 mmol/L): Marked ataxia, mental confusion, nausea, vomiting

• Blood levels 0.3%–0.4% (300–400 mg/dL or 65.1–86.8 mmol/L): Severe dysarthria, amnesia, hypothermia

• Blood levels > 0.4% (400 mg/dL or 86.8 mmol/L): Coma, decreased respiration or respiratory arrest, aspiration of gastric contents, airway obstruction by flaccid tongue, drop in blood pressure and body temperature

What are the behavioral signs & symptoms of opioid intoxication?

• Drowsiness

• sedation

• slurred speech

• impaired memory and attention

• psychomotor retardation

What are the physiological signs & symptoms of opioid intoxication?

• Nausea

• vomiting

• respiratory depression (dose­ related)

• stupor

• coma

• itching

• miosis

• hypothermia

• bradycardia

What are the behavioral signs & symptoms of stimulant intoxication?

• Elated mood

• anxiety

• panic

• impaired judgment

• violent behavior,

• paranoia

• delusions

• hallucinations (tactile or auditory rarely visual)

• increased motor activity

• compulsive or stereotyped

• behavior (eg, skin picking)

What are the physiological signs & symptoms of stimulant intoxication?

• Neurologic/neuromuscular: 

  • Mydriasis, headache, tremor, hyperreflexia, muscle twitching, flushing, hyperthermia or cold sweats, rhabdomyolysis (possibly resulting in renal failure), dyskinesias, seizures, coma

• Cardiovascular: 

  • Tachycardia, hypertension, vasoconstriction, arrhythmias, myocardial infarction, cerebral hemorrhage

• GI: 

  • Nausea, vomiting, weight loss

Which medication can reverse opioid intoxication?

• naloxone 0.4 to 2 mg IV every 2 to 3 minutes up to 10 mg

  •  IM, subcutaneous, or intranasal (IN) route may be used if IV access is unavailable

Pharmacotherapy for stimulant intoxication in acute settings may include which medications?

• benzodiazepines

• aspirin

• nitroglycerin

• nitroprusside

• phentolamine

What are the symptoms of uncomplicated alcohol withdrawal?

• Tremor

• nausea

• vomiting

• tachycardia (> 110 beats/min)

• hypertension (> 140/90 mm Hg)

• headache

• insomnia

What are the symptoms of complicated alcohol withdrawal?

• Seizure activity (usually 1 or 2 generalized tonic­clonic seizures, but can be numerous and possibly fatal)

• Delirium tremens

• Hallucinations (usually visual)

What is the treatment of choice for uncomplicated alcohol withdrawal?

• Benzodiazepines

  • Anticonvulsants, such as carbamazepine, sodium valproate, and gabapentin, have also been evaluated

Which benzodiazepines are most commonly used in the treatment of alcohol withdrawal?

• lorazepam

• diazepam

• chlordiazepoxide

  • Normally used for 3-5 days

Which benzodiazepine is recommended in individuals having compromised liver function?

• Lorazepam → is not metabolized into active compounds

  • Patients with liver disease may still be treated with diazepam or chlordiazepoxide at lower doses

What are the symptoms of opioid withdrawal?

Bad case of the flu

• EENT: lacrimation, mydriasis, rhinorrhea

• GI: nausea, vomiting, diarrhea

• Cardiovascular: increased heart rate and blood pressure

• CNS: irritability, restlessness, yawning

• Musculoskeletal: increased body temperature, piloerection

Which medications might be used in the management of severe opioid withdrawal?

• detox → medically supervised

  • Buprenorphine

    • + naloxone to block opioid receptors

  • Methadone

Which medications might be used in the management of symptom based opioid withdrawal?

• Insomnia: trazodone 75–200 mg at bedtime

• Headache, muscle aches, or pain: acetaminophen 500–1000 mg every 6 hours

• Noradrenergic hyperactivity: clonidine 0.1–0.2 mg every 6–8 hours (not to exceed 1.2 mg in 24 hours), lofexidine 0.54–0.72 mg every 6 hours (not to exceed 2.88 mg in 24 hours)

• Abdominal cramps: dicyclomine 10–20 mg every 6 hours

• Diarrhea: loperamide 2 mg every 6 hours

What are the symptoms of stimulant withdrawal?

• Stage 1: Immediately following binge:

  • Craving, intense dysphoria, depression, anxiety, agitation

• Stage 2: Within 1-4 hours

  • Dysphoria, desire for sleep

• Stage 3: 3-4 days

  • Hypersomnia, increased appetite, craving may dissipate but return later

Are any medications recommended for routine use of stimulant withdrawal?

Medications have been studied to alleviate withdrawal symptoms and cravings, but inconsistent results preclude any recommendations for their routine use

What non-pharmacologic options are available for treatment of substance use disorders?

• Motivation enhancement to stop of reduce substance use

• Coping skills education

• Providing alternative reinforcement

• Managing painful effect (eg, dysphoria)

• Enhancing social support and interpersonal functioning

What 3 medications are FDA-approved for individuals having alcohol use disorder?

• Naltrexone (oral and depot)

• Acamprosate

• Disulfiram

How does naltrexone work?

Acts as a competitive opioid receptor antagonist that decreases alcohol intake, craving for alcohol, and alcohol-induced euphoria (reduces positive reinforcement of drinking)

What is the usual therapeutic dose of oral naltrexone?

• 50 mg once daily, with a range from 25-100 mg

• Long acting IM → 380 mg once daily

What are the common adverse effects of oral naltrexone?

• Nausea

• Headache

• Insomnia

• Nervousness

How many days should naltrexone be withheld after someone stops using opioids?

• Withhold the first dose for 7-10 days after last opioid use 

  • 10-14 days for long-acting opioids

    • Done because Naltrexone can precipitate withdrawal in patients with physical dependence to opioids

Why is it important for individuals taking naltrexone to carry a pocket warning card or wear a medical bracelet?

In the event that emergency pain management is needed, the pateint will be insensitive to opioid analgesia, unless potentially toxic doses are administered

How does acamprosate work?

• A glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist that may affect GABA

  • Alcohol acutely inhibits glutamatergic function → 

  • During acute and postacute withdrawal, increased activity of the glutamate system is caused by upregulation of receptors combined with absence of alcohol-related inhibition → 

  • Acamprosate may correct glutamate/GABA imbalances that occur following chronic alcohol use (reduce negative reinforcement associated with craving and withdrawl)

What is the therapeutic dose of acamprosate?

666 mg orally three times a day

How is acamprosate metabolized?

• Not by the liver, but is excreted unchanged by the kidneys

  • Therefore contraindicated in severe renal impairment (Less than or = to 30 mL/min)

What are the common adverse effects of acamprosate?

• Nausea

• Diarrhea

• CNS effects (insomina, anxiety, and depressive symptoms)

How does disulfiram work?

• Irreversibly blocks the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol

  • This results in increased blood levels of the toxic metabolite, acetaldehyde → As acetaldehyde levels increase, patients experience the disulfiram reaction (s/s: decrease BP, increased HR, chest pain, palpitations, dizziness, flushing, sweating, weakness, N/V, SOB, blurred vision, syncope)

  • Physiologically, disulfiram deters drinking due to knowledge that the disulfiram reactions occurs if alcohol is consumed

What may happen if disulfiram is taken with alcohol?

• Decrease BP

• increased HR

• chest pain

• palpitations

• dizziness

• flushing

• sweating

• weakness

• N/V

• SOB

• blurred vision

• syncope

What is the usual starting dose of disulfiram?

• 250 mg once daily

  • Can be started at 500 mg once daily for the first 1-2 weeks

  • Range is 125-500 mg/day

What are the common adverse effects of disulfiram?

• Rash

• Drowsiness

• Metalic or garlic like taste

  • Less common: 

    • Neruopathies

    • Psychosis

    • Hepatotoxicity

What laboratory parameter should be monitored at baseline and periodically during disulfiram treatment?

• LFTs

  • 3x ULN → repeat testing q1-2 weeks

  • When LFTS return to normal → q1-6 months

What medications are used for opioid use disorder?

• Methadone

• Buprenorphine

• Long-acting naltrexone

Methadone maintenance treatment for opioid use disorder can only be provided in which setting?

Federally approved OTPs (Opioid treatment programs)

How does buprenorphine work?

A partial μ ­opioid receptor agonist

Are there any FDA approved medications for the treatment of stimulant use disorder?

No

What is used prevent Wernicke’s Encephalopathy?

Thiamine

• 100 mg IV, IM, or PO daily for at least 1-4 weeks

What are adjunctive therapies for alcohol withdrawl?

• Hydration and electrolyte replacement

• Antihypertensives

• Antipsychotics

• Antiseizure medications

  • carbamazepine

  • Valproic acid

  • Gabapentin

  • Phenobarbital

What are contraindications for Naltrexone use?

• Opioid use within the last 7-10 days

• Acute opioid withdrawl

• Failure of naloxone challenge

• Positive urine screen for opioids

• History of hypersensitivity to naltrexone

What do you monitor on Naltrexone?

LFTs

How soon can you treat opioid withdrawl symptoms?

As early as 6 hours after the last dose of heroin or short-acting opioids

What medication is used for the treatment of opioid withdrawl symptoms?

• Methadone

• Buprenorphine

• Clonidine

• Adjunctive meds (given PRN)

  • Trazodone, NSAIDs or APAP, dicyclomine, loperamide, hydroxyzine

• Lofexidine

What is the MOA of clonidine?

Alpha 2 adrenergic agonist

• Increases NE and reduces N/V/D, sweating, cramps

What is the MOA of Lofexidine?

Alpha 2 agonist

• Increases NE and reduces symptoms of opioid withdrawl

• Similar to clonidine

Why is suboxone combo given instead of just buprenorphine?

Naloxone helps with reducing misuse potential