SUD Flashcards
Heavy Alcohol Use
Binge drinking on 5 or more days in the past 30 days
When does USE become a DISORDER?
A problematic pattern of substance use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
* Impaired control
* Social impairment
* Risky use
* Physical dependence
Impaired control
- Larger amounts or over a longer period than intended
- Persistent desire or unsuccessful efforts to cut down or control use
- A great deal of time is spent in activities necessary to obtain, use, or recover from substances
Social impairment
- Craving, or a strong desire or urge to use substances
- Failure to fulfill major role obligations at work, school, or home
- Continued substance use despite social or interpersonal problems
- Social, occupational, or recreational activities are given up or reduced because of substance use
What are some symptoms of opioid withdrawal?
- Sweating/chills
- Shakes/tremors
- Muscle aches
- Agitation/anxiety
- Runny nose/eyes
- Yawning
- Insomnia
Why is fentanyl problematic?
- T1/2 2-4 hours
- Transdermal (20-27 hr)
- Fentanyl is HIGHLY lipophilic, leading to concentration in fat tissue and additional considerations during withdrawal management
What are some Withdrawal treatment options for pain, anxiety, diarrhea, and insomnia?
- Pain–> NSAIDs, APAP, Diclofenac
- Anxiety–> Hydroxyzine
- Diarrhea–> Loperamide
- Insomnia–> Trazodone, Melatonin
According to the ASAM National Practice Guidelines for the Treatment of OUD, what is the recommended treatment for abrupt cessation of opioids?
Methadone or buprenorphine
What are the alpha 2 agonist?
Clonidine & Lofexidine
What are the MOA of clonidine & lofexidine?
- Alpha 2 adrenergic receptor agonist
- Symptomatic relief–> Reduced sympathetic outflow from the CNS, decreased peripheral resistance, vascular resistance, heart rate and blood pressure
What is the place of therapy of clonidine & lofexidine?
- Inpatient/outpatient withdrawal management
- ONLY Lofexidine FDA approved
What is the dosing of clonidine?
Clonidine 0.1-0.2 mg every 4 hours PRN based on COWS score–> Limited by ADEs
What are the ADEs of clonidine and lofexidine?
- Orthostatic hypotension
- Sedation
- Dizziness
- Somnolence
- Fatigue
MOA of Methadone
Full agonist at mu opioid receptor
What is the place of therapy of methadone?
Inpatient/outpatient withdrawal management*
Detoxification with methadone can only be done in specially licensed outpatient facilities UNLESS…
* Inpatient and admitted for something other than opioid addiction/withdrawal
* Outpatient prescription for 72 hours to cover patient until entering detox facility
What is the dosing of methadone?
20-30 mg on Day 1 to target withdrawal symptoms–> do NOT exceed 40 mg
* Reduce daily or every other day – usually by about 5 mg daily
What are the ADE of methadone?
- QT prolongation
- Hypotension/orthostatic hypotension
- Dizziness
- Drowsiness
- Constipation
- Nausea/vomiting
- Respiratory
MOA of Buprenorphine
Partial mu opioid receptor agonist with HIGH binding affinity
- Given Buprenorphine’s high binding affinity, it will displace ANY opioids in the patient’s system from opioid receptors and may cause “precipitated withdrawal.” It is important to wait until the patient is experiencing mild-moderate withdrawal before initiation
What is the place of therapy of buprenorphine?
Inpatient/outpatient withdrawal management
What is the dose of buprenorphine?
2 mg every 4 hours PRN based on COWS score
What are the ADE of buprenorphine?
- Hypotension
- Headache
- Dizziness
- Confusion
- Constipation
- Insomnia
- Nausea
What is the maintenance dose of methadone?
80-120 mg once daily
What is the safety of methadone?
- QTc interval prolongation and cardiac arrythmias, and has a higher potential for drug-drug interactions
- Considered a preferred treatment in pregnancy since withdrawal, which lead to fetal distress, is not necessary to start Methadone
What are the risk factors for QTc prolongation?
- Electrolyte abnormalities
- Impaired liver function
- Structural heart disease
- Genetic predisposition
- Use of other QTc prolonging drugs
What are the drug interactions of methadone?
- Alter absorption, metabolism, and/or excretion
- Additive or synergistic sedative or respiratory suppressant effects
- Prolong QTc intervals
What are some clinical pearls of methadone?
- Federal regulations mandate that methadone must be dispensed from designated Opioid Treatment Programs (OTPs)–> Retail pharmacies may only dispense for 72 hours for OUD!
What is the maintenance dose of buprenorphine?
-Dosed daily or BID, titrated to control withdrawal symptoms and cravings
-Usual dosing range is 16-24 mg/day of buprenorphine (before fentanyl ERA)
What is the safety of buprenorphine?
Requires proper administration technique (SL/Buccal) and mouth should be rinsed after use to prevent long-term dental decay
What are the differences between Sublocade (inj-buprenorphine) and Brixadi (inj-buprenorphine)?
Sublocade:
* Lower Injection Tolerability (Forms palpable depot, 1.5 mL SubQ)
* Higher Plasma Concentrations (Well-above levels achieved by SL BUP)
* Not permitted in pregnancy (Contains N-methyl-2-pyrrolidone (NMP)
Brixadi:
* Higher injection Tolerability (No lump, < 0.5 mL, multiple sites)
* Lower Plasma Concentrations (Levels similar to SL BUP formulations)
* “Weekly” Formulation Permitted (NMP is not found in weekly formulation)
What is the MOA of Naltrexone?
Naltrexone is NOT an opioid, but acts as mu opioid receptor antagonist to target the dopamine reward pathway that is mediated by endogenous opioids
What is the efficacy of Naltrexone?
- Extended-release naltrexone may help prevent relapse to opioid dependence in patients who have been successfully detoxed from opioids
- Compared to placebo, naltrexone increases treatment retention and survival
- However, compared to BUP, naltrexone carries a higher risk for opioid relapse and overdose and therefore requires additional caution when prescribing
What are the risk factors of alcohol withdrawal?
- Heavy use
- History of DTs
- Comorbid conditions
- Seizure disorder
- Age 65+
- Long duration of use
What is Severe tolerance and dependence of alcohol?
Patients admitted with BAC > 0.30 and coherent
What are some minor symptoms of alcohol withdrawal?
- Insomnia
- Tremors
- Mild anxiety
- GI upset
- Headache
- Sweating
- Palpitations
- Anorexia
What is the timeline of alcohol withdrawal symptoms?
- Minor symptoms
- Alcoholic hallucinosis
- Withdrawal symptoms
- Delirium tremens (2-3 days after last drink)
Delirium Tremens
- Hallucinations
- Disorientation
- Tachycardia
- Fever
- Hypertension
- Diaphoresis
- Agitation
What are the risk factors of delirium tremens?
- History of sustained drinking
- History of previous DT
- Age > 30
- Concurrent illness
- Significant alcohol withdrawal with an elevated alcohol level (* Longer period since last drink)
What are the kinetics of EtOH?
- Zero order elimination
- NOT concentration dependent
- It takes TIME to clear from the body
What is the MOA of benzodiazepines?
GABA agonists
What is the place of therapy of Benzodiazepines?
The drug in EtOH withdrawal
Symptom Triggered
Reduction in amount of benzodiazepine use, reduced length of stay
Fixed Dose Taper
- Increased benzodiazepine requirement, increased length of stay
What is the fixed dose taper for Benzodiazepine?
- Lorazepam 2 mg three times daily for 48 hours
- Lorazepam 2 mg twice daily for 48 hours
- Lorazepam 2 mg every 2 hours for a CIWA score >= 10 (max combined daily dose of 12 mg)
What is the symptom-triggered withdrawal dose for benzodiazepine?
Lorazepam 2 mg every 2 hours for a CIWA score >= 10 (max combined daily dose of 12 mg)
What is the place of therapy for Phenobarbital?
- Typically reserved for severe withdrawal such as those who fail benzodiazepine therapy or have a history of complicated withdrawal
- Must be initiated in monitored setting
What is the dose of Phenobarbital?
- IV: 230 mg loading dose followed by 130 mg every 4-6 hours as needed
- Oral: 60-120 mg loading dose followed by 30-60 mg every 4-6 hours PRN
What is the PK of phenobarbital?
- Onset: 60 minutes
- Duration: 10-12 hours
- Half-life: 50-120 hours
What is the place of therapy of gabapentin?
- Recommend if plan is to utilize in chronic management (NOT FDA approved)
- NOT recommended in severe alcohol withdrawal as monotherapy
What is the dose of Gabapentin?
- Initial (burst) dose of 1200 mg then 600 mg every 6 hours day 1, tapering by 300-600 mg per day for 4-7 days
- Adjunct therapy: 400 mg every 6-8 hours
What is the PK of gabapentin?
- Onset: 60-120 minutes
- Duration: 4-6 hours
- Half-life: 5-7 hours
What is the place of therapy of Dexmedetomidine?
- Works on NMDA targeting second major neurotransmitter
- Promising new treatment but not widely used at current
What is the place of therapy of Ketamine?
BZD sparing treatment, but easily confused w/ DTs
What is the place of therapy of Carbamazepine?
Never recommended as monotherapy, inferior to BZDs
What is the place of therapy of Baclofen?
Possible use in uncomplicated withdrawal, inferior to BZDs
Wernicke Encephalopathy
- Acute reversible neurologic complication of thiamine (Vitamin B1) deficiency
- Most commonly associated with alcohol use disorder
What are the triad of symptoms for Wernicke Encephalopathy?
- Encephalopathy
- Oculomotor dysfunction (nystagmus)
- Gait ataxia
What is the thiamine replacement for alcohol withdrawal?
- Initiated thiamine 100 mg IM/IV for 3 days
- Thiamine 100 mg orally daily thereafter
What is the thiamine replacement in Wernicke Encephalopathy?
- Immediately initiate thiamine 500 mg IM TID for 2 days, followed by thiamine 500 mg IM daily for 5 days
- Thiamine 100 mg PO daily thereafter if patient improves, clinically, otherwise continue IM
Korsakoff Syndrome
Neuropsychiatric manifestatoin of Wernicke Encephalopathy which develops later if under treated
What are the symptoms of Korsakoff Syndrome?
- Confabulation in some cases (not all)
- Deficits in memory (anterograde and retrograde) as well as apathy
- Intact sensorium and long-term memory/other cognitive skills
What are the anectodal evidence for treatment of Korsakoff Syndrome?
- Continued high dose parenteral thiamine administration (reversal)
- Acetylcholinesterase inhibitors (attention and memory)
- Memantine (attention and memory)
What is the dosage of Naltrexone for the treatment of AUD?
Usual dosage of 50 mg daily
* Some studies show use of 100 mg daily, or 150 mg given three times a week
What are the ADE of Naltrexone?
- GI upset
- Headache
- Dizziness
- Insomnia
- **Elevation in LFTs
- Liver impairment contraindications the use of this medication**
What is the MOA of Acamprosate (Campral)?
Modulates glutamate transmission
What is the dose of Acamprosate?
666 mg (two tablets) by mouth three times daily
* Renal dose adjustment if CrCl 3-50 mL/min: 333 mg TID
* Contraindicated in CrCl < 30 mL/min
* Can be used safely in liver impairment
* Can utilize in concurrent opioid use disorder
What is the dosage of disulfiram?
500 mg daily x 1-2 weeks, THEN
* 250 mg po daily
What are the ADE of disulfiram?
Disulfiram reaction (deterrent for future alcohol use):
* Sweating
* Headache
* Dyspnea
* Hypotension
* Flushing
* Palpitations
* Nausea
* Vomiting
Topiramate
- Treatment for StUD
- Evidence for both cocaine and amphetamine type stimulant
- Caution in underweight patients
Bupropion
- Treatment for StUD
- Evidence for both cocaine and ATS use disorders
- Added benefit in major depression or tobacco use
- Combining with naltrexone beneficial in ATS use
- Caution with seizure or eating-disorder history
Mirtazapine
- Treatment of StUD
- Only recommended in treating ATS use disorder
- Added benefit in major depression, insomnia
- Well-tolerated with minimal adverse effects
ER Mixed Amphetamine Salts
- Treatment of StUD
- Evidence in treating cocaine use disorder (self-reported + UDS abstinence)
- Give additional consideration in those with co-occurring ADHD
- Consider dosing at or above the maximum dose approved by the FDA for the treatment of ADHD to effectively reduce cocaine use
ER Methylprednisone
- Treatment for StUD
- Evidence in treating ATS use disorder (reduced frequency and cravings)
- Give additional consideration in ADHD or those with moderate-high frequency use
- Consider dosing at or above the maximum dose approved by the FDA for the treatment of ADHD to effectively reduce ATS use