Smoking cessation and other addictive drugs

Smoking prevalence

Higher in remote areas, mental illness/high psychological distress (x2), ATSI (2-3x)

M>F

15% ↓ global average

E-CIGARETTES: ↑, 54% tried due to curiosity, 23% use because perceived as less harmful

Smoking Public health strategies

MPOWER package of 6 policies

1) Monitor tobacco use and prevention policies

2) Protect people from tobacco smoke

3) Offer help to quit tobacco use

4) Warn about the dangers of tobacco

5) Enforce bans on tobacco advertising, promotion, and sponsorship

Raise taxes on tobacco

Genetics influence on smoking

Some degree of heritability in:

- Taking up smoking - 50-70% heritability (inconsistent evidence)

- Ability to quit

- Nicotine withdrawal symptoms

- Response to smoking cessation therapies

Gene variants encoding α5, α3, β4 nAChR may affect dependence and smoking quantity

Genes affecting nicotine metabolism (CYP2A6, liver) may affect nicotine dependence

Nicotine withdrawal sx

Daily tobacco use for several weeks

Abrupt cessation/ reduction within 24h followed by ≥4:

- Irritability, frustration, anger (affective sx)

- Anxiety

- Difficulty concentrating

- Increased appetite, bradycardia (somatic symptoms)

- Restlessness (affective sx)

- Depressed mood (affective sx)

- Insomnia

- Anhedonia (affective sx)

Causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Not attributed to another medical condition/mental disorder/withdrawal of another substance/ intoxication

Comprised of somatic (physical) and affective components - escape from affective components (e.g. drug craving) are most important in dependence

Stages of change (when quitting)

- Precontemplation: not ready

- Contemplation: getting ready

- Preparation: ready

- Action

- Maintenance

Lapse: a slip up with a quick return to action or maintenance

Relapse: a full-blown return to the original problem behaviour

Asessment/ indicators of nicotine dependence

Smoking within 30 minutes of waking

- Time to first cigarette = most reliable indicator of dependence

- 'How soon after waking do you have your first cigarette?'

>10 cigarettes per day

- 'How many cigarettes do you smoke each day?'

History of withdrawal symptoms in previous quit attempts

- 'Have you had cravings for a cigarette, or urges to smoke and withdrawal symptoms when you have tried to quit?

Fagerstrom Test for Nicotine Dependence (FND)

5As for smoking cessation

Ask about + document smoking status of all patients

Assess nicotine dependence, barriers to quitting

Advise in a clear, non-confrontational way to quit

Assist - offer smoking cessation, affirm and encourage them, agree on a quit plan, recommend pharmacotherapy id dependent, if not ready use motivational approach

Arrange follow-up contact within a week of quit day, congratulate, encourage review progress/problems, monitor and manage medication AE

Implication of smoking on other med

ANTIPSYCHOTICS

Significant ↑ CYP1A2 activity in heavy smokers (>20 d) = ↑ CL, ↓ plasma conc

- 5 cigarettes may be enough for enzyme induction

- Induces CYP1A2 activity (polyaromatic hydrocarbons in tar) -> affects metabolism of clozapine, olanzapine, fluvoxamine...

- Induces CYP2B6 -> substrates: bupropion, clopidogrel, methadone

Smoking cessation -> rapid exponential ↓ CYP450 activity → ↑ clozapine blood levels -> toxic effects

- A new steady state reached in ≅1 week

- Immediate dose reduction on smoking cessation (10% daily; up to 50%) + TDM + Blood/clinical monitoring for up to 6 months

Nicotine replacement therapy (NRT) moa, treatment regimen

MOA:

Nicotine administered through means other than smoking

Longer time to reach peak plasma conc than cigarettes

Extensive 1st pass metabolism - lower levels

Regimen:

1. SMOKES WITHIN 30 MINS OF WAKING + >10 d

- Nicotine 21mg 24h patch (plus 4 mg gum OR 1 mg spray)

2. SMOKES WITHIN 30 MINS OF WAKING + ≤10 d

- Nicotine 21mg 24h patch (plus 2 mg gum OR 1 mg spray)

3. SMOKES >30 MINS OF WAKING + >10 d

- Nicotine 21mg 24h patch (plus 2 mg gum OR 1 mg spray)

4. SMOKES >30 MINS OF WAKING + ≤10 d

- Nicotine 1.5/2mg lozenge OR 2 mg gum OR 1 mg spray

NRT AE

Usually minor and transient - dizziness, headache, N&V, burning-lip sensation (mouth spray), hiccups, indigestion, abdominal pain, myalgia, cough (inhalation), vivid dreams (especially 24h patch)

May be related to cessation - sleep disturbance, dizziness, weight gain, headache

Patch:

- skin redness, itch, rash - 1% hydrocortisone, rotate application site daily

- insomnia, vivid dreams (24h) - switch to 16h or remove 24h before bed time

Gum, inhalator, lozenge: dyspepsia, nausea, throat irritation - avoid excessive swallowing

Mouth spray: throat irritation, hiccups - delay swallowing

Vaping nicotine liquid: cough, dry throat, nausea, headache - sips of water for dry throat

Varenicline MOA, dose, efficacy

MOA:

Partial ⍺4β2 nAChR agonist

- Binds to receptors -> blocks nicotine -> prevents pleasurable effects of smoking

- Still allows a small release of DA

- Partial agonist activity reduces withdrawal symptoms

Dose: 1 week onset - start ≥7 days before stopping smoking (target quit day: 2nd week of tx)

- 0.5 mg d for 3 days, then 0.5 mg bd for 4 days, then 1 mg bd for 11-23 weeks [as tolerated]

Efficacy

Most effective of all cessation agents keeping people smoke free

- Similar efficacy to combination NRT

- > 2x chances of long term quitting

Varenicline AE, precaution, counselling

AE:

N&V, dyspepsia, constipation, flatulence, abdominal pain, increased appetite, weight gain, headache, taste disturbance, insomnia, abnormal dreams, sleep disorder

Precaution: seizure his, pregnancy, breastfeeding

Brief counselling:

- Nausea: initial dose titration aims to reduce this.

- During/after tx, fast-acting NRT (film, inhaler, lozenge, spray) when strong cravings occur

Bupropion MOA, dose, counselling

MOA

Unknown: Atypical antidepressant - inhibits neuronal DA/NA reuptake (?)

- anti-depressant effects help with depressive symptoms after stopping

- Non-competitive ⍺4β2 nAChR antagonist -> prevents rewarding nicotine effects

Dose:

start ≥7 days before stopping smoking

Initially 150 mg d m for 3 days, then 150 mg bd (at least 8h apart) for 7-9 weeks

Counselling:

- Rash, swelling of lips/mouth, breathing difficulty -> cease and see Dr

- Drink small quantities of alcohol -> can increase risk of fits and other AE

Assess progress throughout treatment - stop drug if no marked smoking reduction

Fast-acting NRT when strong cigarette craving occurs.

Causes false-positive results (amphetamines) with some urine drug screens

Bupropion AE, C/I, precautions

AE

insomnia, nightmares, dizziness, concentration difficulties, agitation, anxiety, tremor, headache, fever, rash, itch, urticaria, anorexia, nausea, dry mouth, constipation

C/I

MAOI in previous 14 days

Precautions

- Seizures

- Bipolar disorder - antidepressant effects may precipitate mania

- Avoid in pregnancy. May consider in BF if non-pharmacological and NRT are inadequate

Illicit/ recreational psychostimulants

methamphetamine, cocaine, estacy (MDMA), canabis

tobacco, caffeine

hallucinogenic psychostimulant

Lysergic acid diethylamide (LSD)

CNS depressant

alcohol

opioid psychostimulant

heroin

needle and syringe programs (NSPs)

· Provide sterile equipment to prevent blood-borne viruses

· Injecting drug users are major mode of HIV transmission

· Rapid outbreaks of HIV occur in cities without NSP

Alcohol MOA

- Positive allosteric modulate GABAA-R (inhibitory receptor; increases GABA-R activity)

- Enhanced action of 5HT-R and 5HT3-R

- Enhanced action of ACh at nACh-R

- Inhibit Ca2+ channels

- Inhibit action of glutamate at NMDA and kainite receptors (inhibitor receptor)

Moderate drinking reduces by 30% mortality associated with heart diseases:

1) Increases high density lipoproteins

2) Inhibits platelet aggregation

Caffeine MOA and pharmacological effects

Methylxanthine

Antagonise adenosine A2A-R -> release of DA, NA, 5HT, ACh, glutamate, GABA

Decreased fatigue -> insomnia

Increased alertness

Performance enhancement

Low doses - pleasant and stimulatory

High doses can produce dysphoria (anxiety, irritability, restlessness)

Diuresis

Stimulation of cardiac muscle

Relaxation of smooth muscle

Small tolerance, almost no withdrawal

Influences to substance use and disorders

CHRONIC RELAPSING-REMITTING BIO-PSYCHO-SOCIAL DISORDER

Influences:

-genetic and epigenetic contribution

-childhood trauma - up to 600% more likely to develop substance use disorders

- childhood stress - propels cascade of effects across neurobiological, endocrine, immune, metabolic, nervous systems -> impacts psychosocial/ cognitive functioning

- pharmacy students - use substances at higher rate + riskier than other student

- Social environment and family

- Support availability

- Health literacy and education

- Healthcare provider behaviour

- Personal behaviour

- Nonmedical use: use of medicines that does not align with the directions of the clinician

Examples of harm minimisation

TARGETING ANABOLIC HARMS (Performance and Image Enhancing Drugs (PEIDs))

- Injecting: technique, site, changing site, supply

- Chemical: purity, adulteration, identity - PEDTEST

- HPA&G axis management: 'time on = time off', minimise adolescent use

- SE management: aromatase inhibitor (eg letrozole)

Alcohol: Thiamine po

Tobacco: Vaping, NRT

Cannabis: Vaping, Oral (oil)

Stimulants: Oral, testing, Hydration

Steroids: IM injecting, HPA axis, Testing

Opioids: Dynamic risk (Rx review), NSP, Naloxone, Therapeutics

Needle Syringe Program (NSP):

- Free sterile equipment: needles, swabs, preparation, disposal

- Strong evidence of benefits to individual and community and huge cost savings

- Prevention cheaper than cure (which is sometimes lifelong suppressive therapy)

NALOXONE: Pure μ-opioid receptor antagonist

- Opioid overdose death = respiratory depression = μ-opioid agonism -> Block μ-agonism = eliminate dynamic effect

- Potent, rapid, predictable, safe

- No contraindications, Harmless in accidental administration

• FREE from pharmacists

• Pharmacist teaches: Identifying and managing overdose, naloxone use

OPIOID TREATMENT PROGRAM:

• Opioid agonist therapy ('opioid substitution')

• Chronic treatment for chronic condition

• Methadone: oral liquid

• Buprenorphine: SL tablet, SL films, or SC depot

• Extremely robust evidence: ↓ costs, ↓community impact, improve health, improve social

• Majority of dosing provided by pharmacists

• Pharmaceutical opioid harm < street opioid harm

Depot Buprenorphine