PHARM 445: Substance Use & Alcohol Use Disorders

what are risk factors for developing substance use disorders

- genetic predispositions

- concurrent disorders (chronic diseases, mental illness, STD risk, obesity etc.)

- trauma/ stress/ childhood adversities (i.e abuse, neglect)

- poverty

- mental health struggles

- drug availability

- negative school atmosphere

- unstable housing/ houselessness

Neuroadaptations exist in three distinct neurobiological stage:

1. intoxication/ binge

2. withdrawal/ negative effect

3. preoccupation/anticipation

What are the main areas of the brain involved in substance use? (3)

1. Basal ganglia (Pleasure & habit forming)

- Nucleus accumbens = motivation; experience of reward

- Dorsal striatum = habit circuitry

2. extended amygdala = stress & negative feelings associated withdrawal

3. prefrontal cortex = executive function-exerting control over substance use

How does the brain change in substance use?

a) disrupts what brain circuits?

b) what do with disruptions cause ... (3)

c) When substance use stops/reduces causes ....

a) disrupts DA circuits in the brain = reduction in D2 receptors = decrease in sensitivity of brain's reward system

b)

- Prioritization of substance seeking behaviours

- Decreases in brain sensitivity to pleasure or reward

- Reduced executive functioning to control impulses, actions, and emotions

c) reduced activation of reward circuit (basal ganglia) AND activation of stress system (amygdala)

what is the 4 central behaviours in the cycle of use

1. impulsivity

2. positive reinforcement

3. negative reinforcement

4. compulsivity

DSM 5-TR Substance-related and addictive disorders 10 drug classes

1. alcohol

2. caffeine

3. tobacco

4. opioids

5. cannabis

6. sedatives, hypnotics or anxiolytics (i.e. benzos, barbiturates)

7. stimulants (i.e. cocaine, methampetamine)

8. inhalants (i.e. nitrites, aerosols, volatile solvents)

9. hallucinogens (i.e. MDMA, psilocybin)

10. other

what are the 2 categories of substance-related & addictive disorders in DSM 5-TR

1. substance induced disorders

2. substance use disorders

what is included in substance induced disorders ?

1. substance intoxication

2. substance withdrawal

3. substance/ medication induced mental disorders :

- EX: psychosis, bipolar, depressive, anxiety etc

what is some of the diagnostic criteria for substance use disorders (hint: 4 overall groupings)

1. Impaired control

- using more substance than intended

- difficulty controlling use

- spending increasing amount of time funding/using/ recovering from the substance

- cravings

2. Social Impairment

- continued use of the substance leading to difficulties meeting personal or professional duties

- continued use despite social problems related to use

- giving up activities because of use

3. Risky use

- using in hazardous situations

- continued use despite causing or worsening mental/ physical health

4. pharmacological criteria

- tolerance

- withdrawal

what 2 criteria for substance use is not enough alone for a diagnosis of substance use disorder

tolerance & withdrawal

severity criteria for substance use disorders

mild = 2-3 sx

mod = 4-5 sx

severe = 6+ sx

what are 4 specifiers for diagnosis of substance use disorder

1. early remission = no sx @ least 3 months but less than 12 months

2. sustained remission = no criteria met at any time for at least 12 months

3. maintenance therapy

4. controlled environment

substance use spectrum

- non use

- beneficial use

- low risk use

- higher risk use

- addiction

what are some protective factors for substance use

- physical safety

- social inclusion

- safe neighbourhoods

- positive school enviornment

- caregiver involvement & monitoring

- stable/permeant/appropriate housing

- healthy behaviour development

treatment services

help reduce or stop substance use by managing withdrawal and

cravings

Ex Includes: counselling/therapy, peer support, medications (for cravings and withdrawal management)

harm reduction services

reduce the negative health, social, and economic impacts of

substance use without requiring abstinence

EX Includes: drug checking services, supervised consumption services, managed alcohol programs, naloxone distribution, safe supply programs

recovery services

process or lifestyle change where people who struggle with substance use concerns work to improve their health and wellness

EX Includes: accessing services/supports that have complete abstinence as a goal OR a variety of harm reduction and treatment services as well as broader social services

what are laws and regulations in place to. help control access to substances

- Controlled Drugs and Substances Act

- Cannabis Act

- Tobacco and Vaping Products Act

- Food and Drug Act

- 3 international drug control conventions (UN Office on Drugs and Crime)

some examples of alcohol related organ damage

- Cardiac = HTN, arrhythmias, cardiomyopathy

- oral cavity

- liver = cirrhosis, hepatitis, cancer, fatty liver

- GI = gut leaking, microbial dysbiosis, colorectal cancer

- Brain = stroke

- lung = pneumonia

- muscle = myopathy

- pancreas = pancreatitis

- bone = reduced bone density

continuum of risk associated with weekly alcohol consumption

LOW = 2 standard drinks or less per week

MOD = 3-6 standard drinks per week

HIGH = 7+ standard drinks per week

Single Alcohol Screening Question (SASQ)

QUESTION: "How many times in the past year have you had 5 or more drinks in a day (for males) or 4 or more drinks in a day (for females)?"

- Brief & no scoring required

- validated in primary care

- sensitive & specificity

AUDIT-C

3 Questions:

1. How often do you have drink containing alcohol?

2. How many units of alcohol do you drink on a typical day when drinking?

3. How often do you have 6+ drinks on one occasion

AUDIT-C scores:

0-4 = low risk for AUD

5-7 = mod risk for AUD

>/= 8 = high risk for AUD

CAGE tool

1. Have you ever felt you should cut down on drinking?

2. Have other people annoyed you by criticizing your drinking?

3. Have you ever felt guilty about your drinking?

4. Have you ever taken a drink in the morning to steady your nerves or to get rid of a hangover? (eye-opener)

5A's for AUD

ASK

ADVISE

ASSESS

ASSIST

ARRANGE

Barriers to this tool = not enough time, not practiced enough or fear of offending pts

alcohol induced disorders

- alcohol intoxication

- alcohol withdrawal

- alcohol induced mental disorders

including: anxiety disorders, sleep disorders, depressive disorders, psychotic disorder & bipolar disorder

Alcohol intoxication

a) definition

b) criteria

a) recent ingestion of alcohol causing significant problematic behaviours or psychological changes shortly after

b) 1 or more during or shortly after alcohol use:

- slurred speech

- incoordination

- unsteady gait

- impairment in attention/memory

- Nystagmus

- supor or coma

alcohol use disorder definition

pattern of alcohol use leading to clinically significant impairment or distress, manifested by at least 2 of the designated criteria within a 12-month period

alcohol use disorder criteria

- consumed in larger amounts over a longer period of time than intended

- persistent desire or unsuccessful efforts to reduce alcohol consumption

- sig. amount of time spend in activities necessary to obtain/ use/ recover from alcohol

- craving

- failure to fulfill major obligations b/c recurrent alcohol use

- recurrent use in physically hazardous situations

- social, occupational or recreational activities are given up

- tolerance

- withdrawal

what are some lab findings someone might see with someone struggling with AUD

- elevated GGT, AST, ALT and or bilirubin

- elevated MCV & decreased folate (macrocytic anemia)

- disturbances in K, P, & Mg

- decreased blood glucose (ketoacidosis possible)

alcohol withdrawal criteria

A) Cessation of (or reduction in) alcohol use that has been heavy and prolonged.

B) Two (or more) of the following, developing within several hours to a few days after the cessation of (or reduction in) alcohol use described in Criterion A:

1) Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100 bpm).

2) Increased hand tremor.

3) Insomnia.

4) Nausea or vomiting.

5) Transient visual, tactile, or auditory hallucinations or illusions.

6) Psychomotor agitation.

7) Anxiety.

8) Grand mal seizures

withdrawal sx present during the following time from alcohol cessation

a) < 6-12 hours

b) 12-24 hours

c) 24-48 hours

d) 48-72 hours

a) hand tremors, N/V, mild agitation, anxiety, insomnia, headaches

b) alcohol hallucinosis (usually resolves after 48 hours)

c) tachycardia, HTN, marked agitation, withdrawal seizures

d) Delirium tremens (disorientation, confusion, severe anxiety), hallucinations, diaphoresis, tachycardia, tremors

Alcohol primarily affects the CNS by acting as a ...

GABA agonist and glutamate antagonist

- disrupts balance = increase inhibitory effects of GABA & suppresses excitatory effects of glutamate

chronic alcohol use brain adaptations

- GABA mediated systems become less sensitive

- glutamate mediated system become hypersensitive

what can increase risk of severe withdrawal from alcohol?

- previous episodes of withdrawal

- current concomitant use of CNS depressants or illicit substances

- recent intoxication

- positive blood alcohol concentration on admission

- increased autonomic hyperactivity

CIWA-Ar

a) indication

b) sx scored (10)

c) scoring

a) assess level/severity of withdrawal symptoms

b)

- Nausea and vomiting

- Tremor

- Paroxysmal sweats

- Anxiety

- Agitation

- Tactile disturbances

- Auditory disturbances

- Visual disturbances

- Headache/fullness in head

- Orientation and clouding of sensorium

c)

mild = < 9

mod = 10-19

severe = > 20

complications/risks of untreated withdrawal

- seizures

- delirium tremens (DTs)

- Wernicke's encephalopathy

- Korsakoff's dementia/syndrome

Wernicke's encephalopathy

a) what is it

b) sx

c) onset

a) Degenerative brain disorder caused by severe thiamine deficiency -- alcohol metabolism increases demand for thiamine

b)

- CNS depression = sluggish, restless, confusion

- wide ataxic gait

- ocular issues = pupil abnormality, nystagmus, hemorrhage

- ↓ BP

- ↓ temperature

c) abrupt onset

________ is essential for glucose metabolism in the brain

Coenzyme thiamine pyrophosphate

Korsakoff's syndrome

a) when dose it occur

b) characteristics

c) recovery?

d) treatment

a) on it own OR after acute phase of Wernicke's

b) Permanent brain damage = persistent psychosis, confabulation, retrograde and anterograde amnesia, difficulty learning & retaining new info

c) majority don't recover

d) antipsychotics, cholinesterase inhibitors, thiamine replacement

goals of treatment for the acute phase of AUD

- Decrease withdrawal symptoms

- Decrease agitation

- Stabilize autonomic hyperactivity

- Decrease seizure risk

- Prevention of serious symptoms: Seizures, DTs, Wernicke's - Korsakoff's syndrome

Prediction of Alcohol Withdrawal Severity Scale (PAWSS)

a) use

b) score < 4

c) score > 4

a) assess risk & help identify pts who may be most at risk for developing severe withdrawal syndrome

b) LOW risk = absence of other contraindications → can consider outpatient/community management; non-benzodiazepines

c) HIGH risk = more intensive monitoring/medical supervision indicated → inpatient management recommended; benzodiazepines most commonly prescribed

Benzodiazepines

a) most common agents used (3)

b) preference for use of different agents

c) Symptom-triggered dosing benefits

a) diazepam, lorazepam, chlordiazepoxide

b)

- diazepam = Seizure prevention, reduction of breakthrough symptoms

- lorazepam = older adults, those with respiratory disease and or hepatic disease (b/c less prone to accumulation)

c)

- better for sedating & anticonvulsant effects

- higher doses given early

- pts improve more quickly; require less medication

what is the typical length of treatment for treating alcohol withdrawal

usually less than 7 days

** Withdrawal management as a intervention is NOT recommended**

what can be given as prevention of Wernicke's/Korsakoff

Thiamine (vitamin B1)

Acamprosate

a) proposed MOA

b) typical dosing

c) when to initiate therapy

d) adjustments are required for ... (2)

e) common AE

f) indication

a)

- restore imbalance b/w glutamate mediated excitation and

GABA-mediated inhibition

- reduce sx associated with withdrawal & modify response to alcohol related cognitive clues

b) 333mg po TID x 3 days then increase to 666mg po TID

c) 4 days after last EtOH consumption

d)

- renal dysfunction (CrCl 30-50 ml/min)

- weight < 60 kg

e) GI upset & abdominal pain

f) more for goal of abstinence

Naltrexone

a) MOA

b) indication

c) dosing

d) CI

e) AE

a) Mu-opioid receptor antagonist

- block euphoria associated with alcohol consumption

- blocks alcohol induced surge. of endogenous opioids = decreases stimulation of DA release

b) preventing return to heavy (binge) or ongoing drinking

c) 25mg po daily x 3 days then increase to 50mg po daily

d)

- acute hepatitis

- severe liver dysfunction (liver failure)

- requiring/taking concurrent opioids

e)

- somnolence

- nausea/ vomiting

- decreased appetite

- abdominal pain

- insomnia

- dizziness

what are alternative pharmacotherapy options for treating AUD? (3)

- topiramate

- gabapentin

- disulfiram