alcohol SUD/stimulant use DISORDER Flashcards

alcohol

tobacco

marijuana

other

true

true

true

 Previous recommendations:
 10 drinks per week for women, no more than 2 drinks on any given day most days
 15 drinks per week for men, no more than 3 drinks on any given day most days

because there is a continuum of risk associated with weekly alcohol consumption

low for individuals who consume 2 standard drinks or less per week.

and moderate for those who consume between 3 and 6 standard drinks per week.

risks increase for those that consume 7 standard drinks or more per week.

true

true

above the upper limit of the moderate risk zone for alcohol consumption-the health risks increase steeply for females than males.

“A problematic pattern of
[substance] use leading to clinically
significant impairment or distress,
as manifested by at least 2 of the
following, occurring within a 12-
month period:”
-Impaired control
- Social impairment
- Risky use
- Pharmacological criteria

1. Alcohol is often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control alcohol use.
3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.
4. Craving, or a strong desire or urge to use alcohol.
5. Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home.
6. Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of
alcohol.
7. Important social, occupational, or recreational activities are given up or reduced because of alcohol use.
8. Recurrent alcohol use in situations in which it is physically hazardous.
9. Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have
been caused or exacerbated by alcohol.
10. Tolerance, as defined by either of the following:
1. A need for markedly increased amounts of alcohol to achieve intoxication or desired effect.
2. A markedly diminished effect with continued use of the same amount of alcohol.
11. Withdrawal, as manifested by either of the following:
1. The characteristic withdrawal syndrome for alcohol (refer to Criteria A and B of the criteria set for alcohol withdrawal).
2. Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms.

Assessment Tool: CAGE

Scoring: Item responses on the CAGE questions are scored 0 for "no" and 1 for "yes" answers, with a higher score being an indication of alcohol problems. A total score of two or greater is considered clinically significant.

AUDIT = Alcohol Use Disorders IdentificationTest

10 questions
Interview or Self-Reported
Developed by the World Health Organization
Must be answered based on STANDARD drinks

- Score 8 or more: Hazardous
Drinking
- Score 13 for females, 15 for
males: Likely presence of
alcohol use disorder

- Answer lies in physiological difference
between the sexes
- Cis-women and people who were Assigned
Female at Birth (AFAB) generally have a
lower % water in their bodies
- Alcohol is water soluble
- Therefore, less alcohol is needed to cause
intoxication
- New research suggests cis-women and
AFAB may produce less alcohol
dehydrogenase than cis-men or people
assigned male at birth (AMAB)

Alcohol
Ingestion
-incr GABA (+ incr Glutamate to compensate)
-Disinhibition/
CNS
depression

inhibition =excitation

GABA and excitation= glutamate

increase

compensating for the depressant effects of alcohol aka the brain decreases inhibitory neurotransmission and enhances excitatory neurotransmission.

by enhancing the function of inhibitory neurotransmitters and neuromodulators i.e GABA, glycine and adenosine

compesatory changes are no longer opposed by the presence of alcohol-balance shifts towards excessive excitation.

seizures

delirium and anxiety

GABA and glutamate

GABA levels drop quickly
glutamate levels remain elevated
Can lead to Delirium Tremens

Absorption- oral absorption is rapid- 5-10 mins after ingestion
Peak = 30-90 mins after last drink depending on type of drink
Food slows absorption and increases time to peak
-Distribution- Vd = 0.6-0.7L/kg, less in women
Metabolism
Ethanol (worked on by Alcohol Dehydrogenase) to acetaldehyde which is worked on by Acetaldehyde dehydrogenase to become acetate CO2 + H2O
▪ Elimination- Primarily renal. Lungs can eliminate up to 10% (rely on this for breathalyzer tests)
▪ Elimination rate = 15-20mg/dL/hour (longer in AUD)

 Slurred speech
 Ataxia
 Disinhibition
 Euphoria (via reward pathway)
 Aggression
 Flushing
 Nausea/vomiting

 Severe intoxication/overdose:
 Blackouts- not creating new
memories
 Coma
 Respiratory depression
 Hypoglycemia
 Hypothermia
 Death

Provide a safe space
 Fluid balance is very important- oral or IV fluids as
tolerated
 Glucose monitoring
 TIME is the main cure for acute alcohol intoxication
 Antagonists not used
 Alcohol poisoning- the person may pass out and not be
able to vomit→ MAY require stomach pumping etc. No
longer routinely done

More than just a hangover
 Can be life threatening
 Body has compensated for chronically
high levels of GABA by increasing release
of excitatory neurotransmitters like
glutamate
 Abrupt removal of alcohol leads to a
rapid drop in inhibitory neurotransmitters
 Excitatory neurotransmitters take time to
down-regulate and reduce
 CNS in an excitatory state
 Delirium tremens, seizures, death

Clinician assessment tool used to
evaluate the level of alcohol
withdrawal
 Helps dictate treatment of
alcohol withdrawal
 Combines clinician observation
and patient reporting
 Validated tool

10

3 consectutive assessments.

ataxia

nystagmus

disorientation, RRless than 10/min or systolic BP less than 100mmhg.

60mg diazepam or 12mg lorazepam in a 12h period

Life threatening condition
caused by severe alcohol
withdrawal due to acute
abstinence or reduction in
consumption of alcohol
 Occurs in ~5% of alcohol
withdrawal patients
 Starts ~48-96 hours after last
drink and lasts ~5 days

Elevated cardiac markers

Increased O2

Hyperventilation → respiratory
alkalosis

Hypophosphatemia

Rhabdomyolysis

Cardiac failure

 Previous DT
 Sustained heavy drinking
 >30y/o
 Concurrent illness
 Significant alcohol withdrawal in the
presence of elevated BAC
 Longer period since last drink (ex.
Person presenting >2 days since last
drink)
 Treat with supportive care, benzos,
treatment of underlying conditions, and
frequent monitoring of symptoms

true

 Non-beverage alcohol is alcohol that is not intended for
human consumption as a beverage.
 E.g. hand sanitizer, mouth wash, aftershave, vanilla
extract
 Marginalized people with severe AUD are often forced to
turn to these forms of alcohol due to inability to afford
beverage alcohol
 Can lead to many harms, including severe intoxication,
blindness, and death (especially if it is not ethanol that is
being consumed)
 A harm reduction approach here would be to provide them
with beverage alcohol.
 More on this later

 Alcohol use disorder
 Different than treating acute withdrawal or
intoxication
 Non-pharm= CBT, group therapy, AA and other
abstinence-based therapies
 Pharmacological = disulfiram, acamprosate,
naltrexone
 All used to help promote prolonged abstinence and
recovery

 Created in USA by Bill Wilson and Bob Smith
 Originally a faith-based program
 Abstinence- based: believe that use of drugs to
help with abstinence (ex. Diazepam for
alcoholism or methadone for opioid use
disorder) dose not constitute true abstinence
 Historically, people who used medications like
above were not allowed in AA/NA
 Newer groups forming with less emphasis on the
“God” aspect and with medications allowed

 Aka Revia®
 Mechanism of action: blocks central µ opioid
receptors
 Doing so blocks the reinforcing nature of
alcohol in the nucleus acumbens (reward
pathway) in the brain
 Also has effect on HPA-axis to suppress alcohol
use
 DOES NOT CAUSE PHYSICAL AVERSION TO ALCOHOL
 If the person drinks, they will not vomit etc
 Rather, helps reduce cravings for, and euphoria
caused by alcohol

50mg daily (often will see
starting dose of 25mg)
 Efficacy:
 Found to reduce alcohol use in
people with AUD better than
placebo in several SR/MA
 E.g. A 2010 Cochrane review
found the RR to be 0.83 (0.76-
0.9) for heavy drinking for
naloxone compared to placebo.
Also reduced drinking days by 4%

 IMPORTANT:
 THIS IS AN OPIOID ANTAGONIST
 Therefore, opioid analgesia will be
ineffective
 CONTRAINDICATED IN COMBINATION
WITH METHADONE- several dangerous
cases have occurred as a result of
naltrexone+methadone combination
 THERE IS NO SITUATION IN WHICH THE
COMBO IS WORTH THE RISK
 ADRs: Nausea, headache, dizziness. Can
cause elevation in LFTs- measure at
baseline and then monthly

 Mechanism of action: not 100% clear
 Postulated to restore glutamate “tone”
 Modulates the neurotransmission of
glutamate upon alcohol use cessation
 DOES NOT DECREASE WITHDRAWAL
SYMPTOMS- pt is still at risk of DTs
 Patients may do better if already
abstinent x 7 days or so- evidence on
this unclear

2x333mg TID (ADHERENCE ISSUE)
 Evidence:
 Murky here too
 Cochrane Review in 2010 of acamprosate vs
placebo showed NNT of 9 for return to ANY
drinking and increased abstinence duration
by 11%. NO effect on heavy drinking
 Other studies have found it to be less
effective
 ADRs: Diarrhea, flatulence, insomnia, anxiety,
depression
 CI in CrCl <30ml/min

▪ Irreversible inhibition of acetaldehyde dehydrogenase (DOA up to 14 days)
▪ Produces severe reaction in combination with alcohol due to build-up of acetaldehyde → approximately 30mins after ethanol exposure
▪ Vomiting, flushing, tachycardia, hypotension, syncope
▪ Reaction severity depends on dose of disulfiram and ethanol

 Considered aversion therapy
 Helps eliminate positive conditioning
associated with drinking- no longer
associated with euphoria but with negative
consequences
 Best if given under supervision or in highly
motivated patients
 Dosing: 125-500mg daily. often done as
500mg daily for 2 weeks then 250mg once
daily thereafter

Evidence = mixed at best
 2014 meta-analysis = disulfiram
no better than placebo for
return to drinking (JAMA. 2014
May;311(18):1889-900)
 Other SR/MA have found time to
first drink and other measures of
abstinence to be no better with
disulfiram than placebo
 No longer commercially
available- must be compounded

 Anti-craving treatments work to reduce reward pathway
activity
 Gabapentin- modulates dopamine. Has good evidence,
especially in combination with naltrexone
 Baclofen- GABA agonist
 Topiramate- modulates GABA system

 MANY
 Liver disease: hepatitis, fatty liver,
cirrhosis
 Wernicke’s encephalopathy, Korsakoff’s
dementia
 Peripheral neuropathy
 Stroke (hemorrhagic)
 Cardiomyopathy
 Arrhythmia
 Cancer
 Impotence
 Esophageal varices

 MANY
 Liver disease: hepatitis, fatty liver,
cirrhosis
 Wernicke’s encephalopathy, Korsakoff’s
dementia
 Peripheral neuropathy
 Stroke (hemorrhagic)
 Cardiomyopathy
 Arrhythmia
 Cancer
 Impotence
 Esophageal varices

Many of these people are homeless or have experienced homelessness
 “Listerine Bums”
 Imagine how awful the disease must be to have a person stealing mouth wash,
cologne, vanilla extract etc. to support stave off cravings and feed their use disorder
 As pharmacists, we need to get away from this demeaning language and refer to
these people as what they are, PEOPLE WHO NEED OUR HELP
 Will be in and out of the justice system- there is little help available to these
folks
 Often spend many nights in the “drunk tank”
 Given a Cliff bar and a bottle of water
 “dry out”
 Sent back out to the street once sober

 ASK, in a non-judgemental way, about people’s drinking
 ASK if they feel they would like to change their drinking habits
 USE the CAGE screening tool to aid your discussions
 KNOW where to refer people when they come to you for help

 CTADS historically combined them into “illicit drugs”

-Cocaine/crack
- MDMA
- Hallucinogens
- Methamphetamine
- Heroin
- Past year use of those 5 drugs was 3% in the 2017 CTADS
 However, methamphetamine use is escalating across the country

true

Personal history of substance use disorder
Family history of substance use disorder
History of psychiatric illness
History of pre-adolescent sexual abuse

“A problematic pattern of [substance] use leading to
clinically significant impairment or distress, as manifested
by at least 2 of the following, occurring within a 12-month
period:”
 Impaired control
 Social impairment
 Risky use
 Pharmacological criteria

Using higher doses and/or
using substance over a longer
period of time than initially
intended.

e.g Taking more hydromorphone
pills than prescribed or continuing to seek them out after rx is finished
“I really need to cut back”

Failure to fulfill major roles
(home, school, work etc)
Avoiding family activities in
order to use

Using in situations that are
physically dangerous or using
despite knowledge of serious
harm
Drinking and driving.
Continued use of cocaine
despite knowledge of
arrhythmia

Increasing doses required to
achieve desired effect
(tolerance). Withdrawal
symptoms occurring when use
abruptly stopped.
e.g Escalating doses of
hydromorphone required to
achieve the “high.” Alcohol
withdrawal syndrome and DTs.

we find SUD at the intersection of

-learned maladaptive coping

-environment

-drug

-genetics

refers to the tendency of a drug to be used in nonmedical situations, even sporadically, due to underlying psychoactive effects it produces (such as euphoria, sedation, or mood changes)” –
Cambridge Cognition

reinforce the neural
pathways/reward system

a learning disorder

Lays down neural pathways that say “stress is more easily managed by
using drug X”

 Alcohol
 Benzodiazepines/barbiturates
 Opioids
 Volatile Solvents

 Cocaine/crack
 Amphetamines
 Caffeine
 Nicotine

 LSD
 Psilocybin (mushrooms)
 Mescaline
 Phencyclidine (PCP)
 Ecstasy (MDMA) (also stimulant)
 Cannabis (also depressant)

food and sex

 Lead to release of ++ neurotransmitters
 Especially NE, Dopamine, Serotonin
 Hijack the reward pathway

MOA: blocks reuptake of catecholamines to the presynaptic neuron
leading to increased concentrations of 5HT, NE, dopamine and
epinephrine in the synapse.

Exogenous activation of the reward pathway→euphoria, insomnia,
increased heart rate, reduced appetite
 Directly cardiotoxic- overdose deaths usually caused by cardiac arrest
 Can lead to extreme increases in core body temperature, which is very
dangerous

<1 minute

peak 3-5 minutes

duration of action 30-60mins

1-5 mins

peak 20-30mins

duration of action 60-120

< 1 min

peak 3-5 minute

duration 30-60 minutes

onset 30-60minutes

peak 60-90

duration - unknown.

 Euphoria/extreme happiness
 ++ Energy
 Mental alertness
 Irritability
 Paranoia
 Bizarre, unpredictable behaviour
 Insomnia

 Vasoconstriction
 Dilated pupils
 Nausea
 Increased BT and BP
 Tachycardia
 Tremors/restlessness
 Muscle twitches

Of snorting: nosebleeds, frequent runny nose, loss of smell, trouble
swallowing
 Of smoking: Cough, asthma, respiratory distress, increased risk of
pneumonia
 Of injection: Increased risk of HIV and Hep C, other bloodborne illness,
endocarditis, skin/soft tissue infections, collapsed veins
 General:
 Malnourishment due to chronic appetite suppression
 Parkinson’s disease after years of use
 Insomnia/restlessness after binges
 Severe paranoia

Overdose:
 Tachycardia
 Hypertensive crisis
 Fever/hyperthermia
 MI
 Death
 Risk of death increases when mixed with other drugs
 Often mixed with EtOH→ party drug
 Heroin + cocaine = speedball = very dangerous and deadly
 No antidote to cocaine overdose- supportive care only

 Withdrawal:
 Anhedonia
 Depression
 Fatigue
 Increased appetite
 Slowed thinking
 Scary dreams and insomnia
 Anhedonia and depression and persist for YEARS after drug
use stops
 Brain needs to re-learn how to experience normal
pleasure

MOA: ++++ dopamine, serotonin, norepinephrine, and epinephrine release in the nucleus acumbens

 Also blocks neurotransmitter reuptake.

rapid via any route (PO, IN,
Inhaled, IM, IV, PR, PV)

 Quickly and easily crosses BBB
 Large Vd of 3-4L/kg

 Injection or smoking: seconds
 Intranasal: 5 mins
 Oral: 20 mins

 Injection or smoking: 30 mins
 Oral: 2-3 hours

 Plasma T1/2 : 12-34 hours
 Effects commonly persist for >24 hours

 Adrenergic activity:
 Tachycardia
 Hypertension
 Hyperthermia
 Wakefulness

 Dopaminergic activity:
 Increased movement
 “Tweaking”
 Euphoria/rewarding feeling

Changes in appetite
 Changes in thirst signal
response
 Changes in mood
(expansive)

 Dopaminergic activity:
 Increased movement
 “Tweaking”
 Euphoria/rewarding feeling

 Increased risk HIV and Hep B&C
 Risky behaviours
 Injury to nerve cells (worsening of
HIV as a result)
 Dental complications (“meth
mouth” see pic)
 Changes in brain structure and
functioning; changes in
dopaminergic pathways
 May be irreversible or may not
recover for a long time after drug
use stops
 Psychosis/hallucinations
 Violent behaviour
 Sleeping problems
 Changes in bone structure
 Overdose = death from cardiac
arrest or due to hallucination

 sense of bugs crawling all over the
skin accompanied by extreme
itchiness.
 Leads to intense sessions of
scratching and subsequent
scabbing and scars.

A sympathomimetic amphetamine

 MOA: Indirect serotonergic agonist- leads to increased concentration of
serotonin in the synapse. Also leads to release of NE and dopamine.
 Similar effects to amphetamines- euphoria

Absorption: readily absorbed from GI tract
Distribution:
 Peak within 2 hours
 Duration: 4-6 hours
Elimination:
 75% excreted intact via urine
 Remainder metabolized via CYP 2D6

With onset of action comes:
 Increased energy/activity
 HTN/tachycardia
 Euphoria/expansive mood
 Closeness with others and increased sexual libido
 Increased trust/empathy
 Nausea
 Muscle cramping
 Chills

 Hyponatremia:
 +++sweating
 +++thirst
 MDMA causes persistent secretion of antidiuretic
hormone which slows water excretion
 MDMA users also often believe that drinking lots of
water will reduce risk of hyperthermia
 All leads to hyponatremia which can be very dangerous

 Serotonin Syndrome:
MDMA is ++ serotonergic
Characterized by a triad of symptoms:
Autonomic dysfunction
Abnormal neuromuscular activity
Altered mental status
Potentially life threatening

 Irritability
 Impulsivity
 Aggression
 Depression
 Sleep problems
 Anxiety
 Memory and attention issues
 Decreased appetite
 Decreased interest in and pleasure
from sex

 Serotonin syndrome
 Hyponatremia
 Hepatotoxicity
 Life-threatening increases in HR, BT, and BP
 No antidote
 Supportive measures only

 Not much to offer folks
 Not a lot of evidence on what to use
 Non-Pharm: CBT, CBT, Group Therapy, Motivational incentives
(aka $$)

(May see):
 Benzodiazepines (diazepam)- issues with efficacy and risk of
developing BZD use disorder
 Methylphenidate or dextroamphetamine (Dexedrine)
 Some emerging evidence that these MAY help with stimulant
withdrawal

Drugs:
 LSD
 Psilocybin
 Peyote
 Dextromethorphan
 Salvia
 PCP and Ketamine (dissociative
hallucinogens)

 Sleep changes
 Hallucinations/delusion
 Change in sexual behaviour
 Changes in perception of time and
place
 Spiritual experiences
 Relaxation
 Paranoia and overt psychosis (short
and long term

changes in pain
perception, perception of past
trauma
 Some being studied for tx of
tx resistant depression etc

 Flashbacks to when patient
was on hallucinogen
 Happen without warning
 Can happen days to years
after last drug use

 Hallucinogen use disorders are in the DSM-V
 However, there is some debate about whether a true hallucinogen use disorder can occur at a brain level
 They do not cause a release of NTs in the nucleus acumbens
 They do not then “hijack” the reward pathway
 Without doing that, can a person have a true use disorder?
 Rarely hear of someone using LSD over and over again to the detriment of their
family, work, or school commitments
 Hallucinogens are often taken in addition to other substances
 Those substances are usually the ones for which the person has the true use disorder
 Food for thought!

Solvents (become gas at RT)
 Aerosol sprays
 Gases (including petroleum gas)
 Nitrites (ex. Nitroglycerine)
 Work to slow/reduce brain activity

 Slurred speech
 Ataxia
 Euphoria
 Dizziness

 Liver and kidney damage
 Hearing loss
 Bone marrow damage
 Loss of coordination
 Muscle damage
 Delayed behavioural development
 Brain damage

 Not much to offer folks
 Not a lot of evidence on what to use
 Non-Pharm: CBT, CBT, Group Therapy, Motivational
incentives (aka $$)