5.12 pharmacotherapy of substance use disorders Flashcards
How does the DSM5 define substance use disorder?
Problematic pattern of substance use leading to clinically significant impairment or distress, with having two of the following occurring in a 12 month period:
- Taken in larger amounts; over a longer period than intended
- Persistent desire or unsuccessful efforts to control use
- Great deal of time spent in activities necessary to get substance or recover
- Craving, urge to use
- Recurrent use results in failure to fulfill major obligations
- Continued use despite social or interpersonal problems
- Continued use even though it’s hazardous
- Continued use despite realizing it’s harmful
- Tolerance
- Withdrawal
What is the presentation of having a BAC of 50 mg/dl (0.05 mg%)?
Motor function impairment observable
What is the presentation of having a BAC of 80 mg/dl (0.08 mg%)?
- Moderate impairment
- Legal definition of intoxication in most states
What is the presentation of having a BAC of 450 mg/dl?
Respiratory depression
What is the presentation of having a BAC of 500 mg/dl?
- LD50 for ethanol
- Lethal
What is the time of onset after withdrawal for alcohol withdrawal stage 1?
6-8h
What clinical features are present w alcohol withdrawal stage 1?
- Moderate autonomic hyperactivity (anxiety, tachycardia, nausea, insomnia)
- Craving for alcohol
What is the time of onset after withdrawal for alcohol withdrawal stage 2?
24h
What clinical features are present w alcohol withdrawal stage 2?
- Autonomic hyperactivity w auditory or visual hallucinations lasting 1-3 days
- Most remain lucid and oriented
What is the time of onset after withdrawal for alcohol withdrawal stage 3?
1-2 days
What clinical features are present with alcohol withdrawal stage 3?
4% of untreated pts develop grand mal seizures 7-48h after drop in BAC
What is the time of onset after withdrawal for alcohol withdrawal stage 4?
3-5 days
What clinical features are present w alcohol withdrawal stage 4?
Delirium tremens (DTs) in 5% of pts (confusion, illusions, hallucinations, agitation, tachycardia, hyperthermia)
What are risk factors for delirium tremens?
- Prior hx of DTs (#1 predictor of future DTs)
- # of detoxifications
- Consuming equivalent to 1pint of whiskey/day for 10-14 days prior to admission
- Early sxs of withdrawal
- Hepatic dysfxn
Pts w DTs can experience something called kindling. What is kindling?
Repeated withdrawal episodes increases the severity of subsequent withdrawal syndromes
What is the prophylaxis/fixed dosing tx of alcohol withdrawal?
- No liver dysfxn: diazepam, chlordiazepoxide, lorazepam, oxazepam
- W liver dysfxn: lorazepam, oxazepam
- May also use lorazepam PRN to supplement
What is the advantage of using a prophylaxis/fixed dosing tx for alcohol withdrawal?
Prevent withdrawal
What is the disadvantage of using a prophylaxis/fixed dosing tx for alcohol withdrawal?
Unnecessary BZD dosing
What is the individualized dosing tx of alcohol withdrawal?
- CIWA <8: Nonpharm tx
- CIWA 8-15: Medicate
- CIWA >15: Risk of complications if untx
- No liver dysfxn: diazepam, chlordiazepoxide, lorazepam, oxazepam
- W liver dysfxn: lorazepam, oxazepam
Should phenytoin be used for alcohol withdrawal?
- Takeaway: phenytoin doesn’t work
- Not effective to tx withdrawal seizures
What is always recommended if there is any suspicion of alcohol abuse?
Thiamine 100mg daily, usually duration of hospital stay –> reduce risk of Wernicke’s
What is Wernicke’s a result of?
Thiamine deficiency
When should thiamine be given?
Give before dextrose-containing fluids
Why is thiamine required to prevent Wernicke’s?
- Thiamine is a cofactor in glucose metabolism
- Wernicke’s can be precipitated by high glucose loads
What other drugs are used for alcohol use disorder?
- Disulfiram (Antabuse)
- Acamprosate (Campral)
- Naltrexone
What is disulfiram (antabuse) used for?
Aversive therapy for alcohol withdrawal
What does disulfiram (antabuse) cause?
Unpleasant effects if alcohol is used
What is a risk w disulfiram (antabuse)?
Potential for CV collapse, death w excessive alcohol
What happen after disulfiram (antabuse) d/c?
- Disulfiram rxn for up to 14 days after d/c
- Bc aldehyde dehydrogenase inhibition irreversible
What is acamprosate (campral) used for?
Maintenance of alcohol abstinence
How is acamprosate (campral) eliminated and why is this important?
- Renal elimination, monitor renal fxn
- IMPORTANT: avoid in severe renal impairment
What is a warning with acamprosate (campral) and SEs?
- Suicidality warning
- Diarrhea, nausea, depression, anxiety
What is naltrexone cause?
Decreases binge drinking, helps to increase time between drinking days
What is common w naltrexone use and must be monitored?
- Elevated LFTs common
- Must monitor at baseline and routinely
What must be evaluated w naltrexone use and why?
- Evaluate pain management needs
- Pt should have card or be able to tell providers they are on naltrexone bc naltrexone is an opioid antagonist
What is a warning for naltrexone?
Injection site rxns
What is the tx for muscle aches/tension of opioid withdrawal?
Acetaminophen or NSAID
What is the tx for agitation/anxiety/insomnia of opioid withdrawal?
Hydroxyzine/benzos
What is the tx for abdominal cramping/nausea/vomiting of opioid withdrawal?
Ondansetron
What is the tx for diarrhea of opioid withdrawal?
Loperamide
What is the tx for sweating/yawning/increased tearing/runny nose of opioid withdrawal?
Clonidine or lofexidine
What are alpha2 agonists used for in opioid withdrawal sxs?
Treating noradrenergic sxs can serve as entry to longer-term tx w MOUD and psychosocial tx
What are the alpha2 agonist drugs used in opioid withdrawal tx?
- Clonidine
- Lofexidine
What is the most common SE w clonidine?
Hypotension
Which drugs are maintenance tx for opioid use disorder?
- Methadone
- Buprenorphine
What is a requirement for dispensing of methadone?
Methadone must be given in a licensed tx program
How is buprenorphine usually given and why?
- In combo w naloxone in a SL tablet or film strip dosage form
- Poor bioavailability when swallowed, must be SL
What CYP interactions does methadone have and what are cautions due to it?
- P450 2B6, 3A4, 2C19, 2D6 substrate
- Use w caution in pts also taking moderate to strong inhibitors or inducers
What is a serious concern w methadone and must be monitored?
- QTc prolongation is a serious concern
- ECG monitoring is recommended
When should buprenorphine therapy be initiated?
- To avoid precipitating withdrawal, initiate therapy when there are clear signs of withdrawal
- Admin in divided doses on day 1
What must be monitored w buprenorphine use?
- Monitor LFTs
- Use w serotonergic drugs may cause serotonin syndrome
What is a lesser concern w buprenorphine use and why?
- Risk of respiratory depression in OD is much less than w opioids, including methadone
- Due to partial agonist effect
What is buprenorphine extended-release injection used for?
For moderate-severe opioid use disorder
How is buprenorphine extended-release injection administered?
Pts initiated on SL buprenorphine and dose adjustments for at least 7 days prior to 1st injection
When is methadone more preferable?
- More effective
- FDA approved for use in pregnancy
When is buprenorphine more preferable?
Effective in tx over short term
When is naltrexone long-acting injection a good choice?
For pt w alcohol AND opioid use disorders
What is common w substance withdrawal?
Depression
- May last for months after d/c of cocaine
- Tx like clinical depression
