AUD 2 Flashcards
Goals of treatment
Acute phase
● Relief of symptoms (objective and subjective)
● Prevention:
○ Seizures
○ DTs
○ Wernicke’s - Korsakoff’s syndromes
Long term
● Medical assessment
● Treatment program, relapse prevention, harm reduction
Wernicke’s encephalopathy
● Abrupt onset - prevention is essential!
● Secondary to severe thiamine deficiency
○ ↓ food consumption, ↓ absorption, impairment of storage in liver
● CNS depression - sluggish, restless, confusion, coma
● Ambulatory difficulties - wide ataxic gait
● Ocular issues - pupil abnormality, nystagmus, hemorrhage, papilledema
● Autonomic instability - ↓ BP, ↓ temperature
Korsakoff’s dementia
● “Survivors of Wernicke’s”
● Occurs after acute phase of Wernicke’s
● Permanent brain damage
● Persistent psychosis, confabulation, retrograde and anterograde amnesia
● Majority do not recover - prevention is essential
Treatment: antipsychotics, cholinesterase inhibitors, thiamine replacement
Prevention of Wernicke’s - Thiamine (vitamin B1)
● Individuals with AUD have impaired absorption and may have impaired
conversion to pyrophosphate (active form)
○ Alcohol metabolism raises the demand for thiamine
○ Poor nutrition decreases the supply of thiamine
○ Coenzyme thiamine pyrophosphate essential for glucose metabolism in the brain
● Given to prevent Wernicke-Korsakoff encephalopathy
○ Series of symptoms that occur due to the inability to metabolize glucose (due to thiamine
deficiency)
○ Always give thiamine before giving glucose
■ Prevent potential severe and irreversible cerebral and brain stem damage
● Dosing:
○ Severe withdrawal: 500mg IV q8h x 72h, then 300mg IV x 3 days, then 100mg po daily
○ Mild-moderate withdrawal: 300mg IV (or 250mg IM) x 3 days, then 100mg po daily
Treatment - Withdrawal
goals
Goals:
● Decrease withdrawal symptoms
● Decrease agitation
● Stabilize autonomic hyperactivity
● Decrease seizure risk
Start treatment when symptoms appear based on individualized scoring (CIWA)
Benzodiazepines - first choice
Treatment - Withdrawal
● Benzodiazepines have equal efficacy but different considerations
● Preference for long acting agents
○ Seizure prevention, reduction of breakthrough symptoms
● Increased risk of addiction with diazepam, alprazolam, and lorazepam due to
fast onset
Most common agents: diazepam, lorazepam, chlordiazepoxide
● Symptom-triggered dosing of benzodiazepines
○ Symptom-triggered dosing has been shown to be more effective than fixed-dosing
■ For both sedating and anticonvulsant effects
■ Higher doses given early along with close monitoring of CIWA scores
■ Patients improve more quickly; require less medication overall
■ Lorazepam = elderly patients, those with respiratory disease, and/or hepatic disease
● No active secondary metabolites
● Dosing is usually aggressive
○ Limited by sedation, confusion, decreased respiratory rate
○ Some providers may use loading doses as well
● Monitor regularly with CIWA assessments
Treatment - Withdrawal
length of tx
monitoring
● Length of treatment: usually less than 7 days
○ In community - may see more structured treatment
■ For example: PRN dosing x 24 hours, then divided doses x 24-48 hours, taper over 3-5
days
● Monitoring:
○ Efficacy - CIWA score, breakthrough symptoms
○ Safety - sedation, confusion, dizziness, vitals
Acamprosate
● Mechanism of action not well understood
○ Believed to restore imbalance between glutamate mediated excitation and GABA-mediated
inhibition of neural activity and to reduce general neuronal hyperexcitability
○ Thereby thought to reduce symptoms associated with withdrawal and modify response to
alcohol related cognitive clues
● Found to significantly reduce likelihood for returning to any drinking by 14%
and increased cumulative duration of abstinence by 11 days compared to
placebo
● Predictors of positive response - completing withdrawal management, having
abstinence as a treatment goal, higher baseline anxiety levels, physiologic
dependence, lack of family history, later age of onset (>40 y/o
Acamprosate
● Typical dosing
● Typical dosing: 333mg po TID x 3 days then increase to 666mg po TID
○ Most guidelines suggest to initiate therapy 4 days after last EtOH consumption
○ Adjust for renal dysfunction and/or weight < 60kg
■ CrCl 30-50mL/minL ↓ 50% dose; avoid below 30mL/min
■ Wt < 60 kg - BID dosing
● Most common side effect: GI upset
● TID dosing/pill burden often barrier to adherence
● Pregnancy: category C - benefit versus risk assessment
● Coverage: special authorization required for ABC plans; open benefit NIHB
Preferred tx
most guidelines suggest that we initiate therapy for days after the last alcohol consumption, which is typically once this withdrawal picture has mostly cleared,
dosing is titrated like this because the most common side effect is some GI upset. So that lower dose for the first couple of days helps people adjust
TID is hard to manage, pill burden increased
Reasonable choice in pregnancy depending on benefit vs risk
s almost $200 a month without coverage
Basically no drug int
Naltrexone
● Mu-opioid receptor antagonist
○ Shown to block euphoria associated with alcohol consumption
■ Blocks alcohol induced surge of endogenous opioids, decreasing the stimulation of
dopamine release (rewarding effect)
○ Evidence supports: ↓ relapse rates, ↓ # of drinking days, ↓ cravings
○ Effective at preventing return to heavy (binge) or ongoing drinking
● Predictors of positive response - high levels of cravings, family history of AUD
it reduces that rewarding effect and ideally, or it is hypothesized that over time then helps to reduce our cravings for alcohol.
evidence mostly supports naltrexone for people with binge drinking patterns
● Typical dosing: 25mg po daily x 3 days then increase to 50mg po daily
○ Mostly studied as daily dosing
○ Some RCTs show that PRN dosing can be effective
● Contraindicated in acute hepatitis, severe liver dysfunction, and/or those
requiring/taking concurrent opioids
● Most common side effect: GI upset (nausea - 10%), mood (depression - 5-7%),
hepatotoxicity
● Pregnancy: category C - benefit versus risk assessment
● Coverage: open benefit for ABC plans and NIHB
Disulfiram
● Alcohol deterrent therapy
● Inhibits metabolism of alcohol by blocking acetaldehyde dehydrogenase
○ Causes acetaldehyde to build up → “disulfiram reaction”
■ Flushed skin
■ N&V
■ Headache
■ Tachycardia
■ Weakness
■ Hypotension
■ Confusion
■ Diaphoresis
○ Reaction can occur promptly after alcohol ingestion; may last for several hours
○ Severe reactions: MI, CHF, arrhythmias, respiratory depression, seizures, and death
The reaction can occur anywhere 10-20 min after your first dose. But then it can actually last up to two weeks after your last dose.
the studies have not shown significant advantages over placebo in terms of achievement of total abstinence and delay of relapse
while you do still have this chance for some effects afterwards, not everyone has that. So as soon as you stop taking the medication, there’s the potential that then like any benefit you were deriving from Disulfiram is lost.
Disulfiram
● Typical dosing
● Typical dosing: 250mg po daily; may increase to 500mg po daily
○ Start at least 36 hours after last drink
● Important to receive appropriate counseling
○ Ensure awareness of “disguised” forms of ethanol (cough syrups, mouthwash)
○ Duration of drug activity (up to 14 days)
● Contraindicated in severe myocardial disease or coronary occlusion
● Most common side effect: poor after taste, dermatitis, hepatitis, N&V, headache
● Pregnancy: not studied
● Coverage: not commercially available in Canada, requires compounding
any patient who has myocardial disease or has had any kind of cardiac history, this would probably be not an agent that we would want to risk because of the potential cardiac complication that can occur with the disulfiram reaction
Knowing that for a lot of people, like complete abstinence, it’s very difficult to achieve, especially in our society where alcohols so accessible and so normalized, it might not be, it might take a couple of times before we get there until a medication like disulfiram reaction could have very grave consequences
emphasize this potential for the reaction to occur up to two weeks after the last dose
potential sources of disguise alcohol. So this can include certain types of cough syrups, mouthwash
not studied pregnancy and I feel like it would be like the potential risks here would be hard to kind of outweigh it.
Gabapentin
● Off label
● Emerging evidence for outpatient withdrawal management for patients at low
risk for severe withdrawal
● Three RCTs (up to 600mg po TID) - small to moderate effects on abstinence
and heavy drinking outcomes, cravings, mood, and insomnia compared to
placebo
● Caution in geriatric patients, pregnant patients, concurrent use of other CNS
depressants, renal impairment, compromised respiratory function, cognitive
impairment
Topiramate
● Off label use
● May reduce dopamine release - ↓ alcohol cravings
○ Thought to alter GABA function at a non-BZD site on the GABA-A receptor and antagonize
glutamate activity
● Reduces heavy drinking days
● Most common side effects: paresthesia, anorexia, pruritus, difficulty
concentrating, somnolence, fatigue, confusion
● Typical dosing: 300mg po daily or 150mg po BID
Managed Alcohol Programs (MAPs)
● To support individuals with active, severe alcohol use disorder
○ In the acute care context: to support patients to stay in hospital for required treatment(s) where
forced detoxification is harmful and abstinence is not a realistic short term goal
● Typically, provide prescribed doses of alcohol at regular intervals
● Intoxication assessment prior to each dose
● Acute care models are inherently more medicalized than community based
MAPs
National guidance documents in progress…
Idea of managed alcohol programs in the community is to help reduce non-beverage alcohol use. And so this is the practice of consuming liquids like rubbing alcohol, mouthwash, hairspray, hand sanitizer on some cooking wines or even cologne. And so we know that these non-beverage forums are very dangerous and have a risk of a lot of toxic effects and potential poisoning. But sometimes people will turn to using these forms of alcohol because they’re more accessible, there may be more cost-effective and they’re sometimes more widely available than some alcoholic beverages.
support patients to transition to like regulated forms of alcohol
dispensed alcohol provided to them and measure doses and measured frequencies
