Smoking

Smoking prevalence

Alarming prevalence - 1.3 billion smokers worldwide

Contributing to over 8 million deaths worldwide each year and significant health associated complications

Major cause of preventable morbidity and mortality in the developed world

Smoking in Australia

11.1% daily smokers aged > 18 years

20,000 deaths annually

Over $32 billion in health, social and economic costs

7.6% of the total burden of disease and injury

70% of total disease burden from lung cancer and chronic obstructive pulmonary disease (COPD)

Smoking facts

Contributing death of one-third to one-half of all lifetime users.

Kills more than AIDS, legal drugs, illegal drugs, road accidents, murder and suicide combined

Hundreds of thousands of deaths annually associated with second-hand smoke

Nicotine dependance

• Mental, behavioral or neurodevelopmental disorders dur to substance use

• Chronic condition (similar to diabetes and hypertension)

• Characterized by remission and relapse

• Hard to cure

Nicotine dependance

• Classified as ‘tobacco use disorder’ in DSM-V

• Presence of at least 2 of the following criteria:

• Impaired control: taking more or for longer than intended. Unsuccessful efforts to stop or cut down use. Spending a great deal of time obtaining, using or recovering from use. Craving for the substance

• Social impairment: failure to fulfil major obligations due to use. continued use despite problems caused or exacerbated by use. Important activities given up or reduced because of substance use

• Risky use: recurrent use in hazardous situations. Continued use despite physical or psychological problems that are caused or exacerbated by substance use

• Pharmacological dependance: tolerance to the effects of the substance, withdrawal symptoms when not using or using less of the substance

Pharmacokinetics of nicotine

• Colorless and odorless naturally occurring alkaloid

• Short half-life of 40-120 min

• Whole life up to 20 hours

• Nicotine is the most addictive but not the most harmful substance in a cigarette

Pharmacokinetics of Nicotine

Nicotine plasma concentration range 10-80 ng/ml

Nicotine plasma concentration range 20-35 ng/ml for regular smokers

Pharmacokinetics of Nicotine

• Metabolized by CYP2A6 mainly, CYP2B6, CYP2E1 and CYP1A2

• Cotinine: nicotine’s major non-addictive metabolite

• Induction of CYP1A2 and CYP2B6 by smoking (via chemicals in cigarette smoke such as polycyclic aromatic hydrocarbons)

• Major tobacco-associated drug interactions

Common Tobacco-drug interactions

Pathophysiology of Dependance

• Absorption of nicotine by the respiratory tract

• Rapid absorption into the pulmonary venous circulation

• Reaches brain in less than 10-20 sec

Pathophysiology of Dependance

• Activation of dopaminergic receptors- DA release

• Widespread neuronal activation by nicotine and dopamine

• Release of rewarding neurotransmitters

Pathophysiology of Dependance

• Desensitization and upregulation of receptors with chronic exposure

• Tolerance

  • Decreased responsiveness to nicotine as body adapts to its presence

  • Increasing dose of nicotine required to obtain same effects

• Dependance

  • Withdrawal symptoms upon reduction or abstinence

  • Strong tendency to relapse post quitting

Withdrawal symptoms

Increased noradrenergic outflow secondary to deactivation of reward system

More smoking & failed quit attempts

Chemicals in a cigarette

• 4000 toxins inhaled/cigarette smoked

• >40 clinically proven carcinogens

• Polycyclic aromatic hydrocarbons and Nitrosamines - DNA damage

• Hundreds of additives and flavorings

• Detrimental effects on:

  • Vital organs

  • Immune system

  • Key body functions

  • Life expectancy

Health effect of smoking

Benefits of smoking

24 hours: Lungs starts to clear out mucus and other smoking debris

48 hours: Carbon monoxide is eliminated from body. The senses of taste and smell are improved

72 hours: Breathing becomes easier. Bronchial tubes start to relax. Energy levels increase

2-12 weeks: Circulation improves

3-9 months: respiratory problems improve as lung function is increased by up to 10%

1 year: Risk of heart attack decreases by half that of a continuing smoker

10 years: Risk of lung cancer decreases by half that of a continuing smoker

15 years: Risk of heart attack becomes similar to someone who has never smoked

Quitting before or during pregnancy: Risk of miscarriage, preterm delivery, low birth weight baby and sudden infant death syndrome decrease.

Smoking Cessation in Pharmacy - Role of pharmacists

Apply the 5As of quitting

• Ask the patients if they use tobacco products

• Advise them to quit

• Assess their nicotine dependance level and their willingness to quit

• Assist with pharmacotherapy and counselling

• Arrange follow up to prevent relapse

Role of pharmacists: Applying the 5Rs of quitting- For patients unwilling to attempt quitting

• Relevance: Why quitting is relevant to their health scenario

• Risk of ongoing smoking habits

• Rewards: benefits of smoking cessation

• Roadblocks or impediments to quitting (withdrawal symptoms, fear of weight gain, social situations)

• Repetition: most need multiple quit attempts

Role of pharmacists-Brief intervention

• Applying the AAH

• Ask the patients if they use tobacco products

• Advise them to quit and advise that using pharmacotherapy and behavioral interventions is the most effective way

• Help by offering pharmacotherapy and referral to behavioral pathways such as quilting

Assessment of Nicotine Dependance

Fagerstrom test for nicotine dependance

Heaviness of smoking Index (HSI)

Expired CO levels using a CO monitor

Carboxyhemoglobin levels (COHb)

Urinary, saliva or blood cotinine levels

Fagerstrom test

Heaviness of Smoking index

it’s not about the number of cigarette but the criteria

Assessment of willingness to change

Stages of change model

Pharmacological interventions

• Nicotine replacement therapy (NRT)

  • Gums

  • Lozenges

  • Transdermal patch

  • Quick Mist mouth spray

  • Inhalator (being discontinued)

  • Nasal spray (not available in Australia)

• Varenicline

• Bupropion

• Others: Cytisine

When you would you recommend applying the patch as it has a side effect of vivid dreams?

at night because it’s a slow-release formulation, it’s peak will be in the morning. the smoker will be awake and won’t experience these side effects

Nicotine Replacement Therapy

• Equal efficacy of all forms of NRT

• Nicotine delivery effects (in decreasing order)

  • Cigarette

  • Spray

  • Inhalator

  • Lozenge/Mini Lozenge/Gum

  • Patch

• Smoking while on NRT is NOT contraindicated

Instructions for use - GUM

Chew 1 piece of gum slowly, until flavors become strong or a slight peppery tingling sensation is felt

Park between the cheek and gum

Chew again when flavor fades

Repeat until there is no more tingling for about 30 minutes

Instructions for use - Lozenge

• Place lozenge between the cheek and gum, suck slowly until taste is strong

• Stop sucking until taste fades, resting the lozenge against the cheek

• Continue to suck again when taste fades

• Move lozenge occasionally from side to side

• Repeat until lozenge has completely dissolved

• The whole process should take 20-30 minutes for lozenges and 10-13 minutes for mini lozenges

Instruction for use - Mouth spray

• Point the spray nozzle towards the open mouth, holding it as close as possible

• Press the top of the dispenser to release one spray into the mouth, avoiding the lips

• For best results, avoid swallowing for a few seconds after spraying

Instructions for use- Inhalator

• Insert cartridge into mouthpiece

• Take a shallow puff every 2 seconds or take 4 deep puffs every minute

• Continue for up to 20 minutes

• Replace cartridge

Instructions for use - Patch

• Apply the path in the morning or bedtime

• Remove before bedtime if applied in the morning or remove in the morning if applied at bedtime (16 hours) or replace the next day (24 hours)

• Patches should be applied to clean hairless skin on chest or upper arm

• Rotate site each day

• Do not cut patches in half

• Swimming and bathing are allowed 1-hour post-application

Nicotine replacement therapy

• Combination therapy more effective than monotherapy

• Double successful quit rates with combinational NRT

• Establishes safety

• First line pharmacotherapy = Varenicline

Varenicline

Dosage form:

• Prescription only

• 0.5 mg (white) & 1 mg (blue) oral tablets per pack

• Day 1-3: 0.5 mg daily

• Day 4-7: 0.5 mg twice daily

• Day 8 - week 12: 1 mg twice daily

Benefits:

• Partial agonist acting centrally on a4b2 nicotine receptors, simulating dopamine release, thus reducing cravings and withdrawal symptoms

• Antagonist preventing stimulation of receptors by nicotine, thus decreasing the pleasurable effects achieved from smoking and the risk of full relapse after temporary lapse

• 3-fold increase in odds of successful long-term quitting as compared to pharmacologically unassisted attempts

Adverse effects:

• Mild to moderate nausea in 30% of patients, generally diminishing with time

• Headache

• Insomnia

• Vivid dreams

• Reports of serious neuropsychiatric events including depression and suicidal thoughts in some patients.

Precautions / contraindications:

• Cautions in patients with underlying psychiatric illnesses - Monitor closely

• Dose adjustment in severe renal impairment

• Not recommended in pregnancy, breastfeeding and in smokers under the age of 18 due the lack of conclusive evidence

• Contraindicated in hypersensitivity to any ingredient

  Comment:

• Recommended 12-week course of therapy for increased chances of success

• No significant increase in CV adverse effects

• Equally effective to combination NRT

• Available on PBS

Bupropion

Dosage form:

• Prescription only

• 150 mg tablets

• 150 mg for 3 days

• 150 mg BD for the remaining 53 days (7.5 weeks)

Benefits:

• Selective dopamine/norepinephrine reuptake inhibitor, thus reducing cravings and nicotine withdrawal symptoms

• Nicotinic receptor antagonist

• Double the success rates of quitting at 6 months as compared to placebo

• Efficacious in patients with depression, cardiac and respiratory diseases

Adverse effects:

• Insomnia

• Headache

• Nausea

• Dry mouth

• Dizziness

• Anxiety

Precautions / contraindications:

• Seizure/epilepsy

• Head injury

• Brain tumors

• Past/current history of anorexia / bulimia nervosa

• pregnancy and lactation

• Patients under 18 years of age

• Concomitant or recent use within the last weeks of MOA inhibitors

• Severe hepatic diseases

• End-stage renal disease

• Acute withdrawal from benzodiazepines or alcohol

• Hypersensitivity

  Comments:

• Less frequently prescribed antidepressants for smoking cessation

• Highest success rates when prescribed with NRT - monitor for blood pressure

• Recommended therapy for 8-12 weeks

• Available on the PBS

Cytisine

• Inexpensive plant derived alkaloid

• Partial nicotinic receptor agonist (a4b2 subunit)

• Approved and used in Central and Eastern Europe and Central Asia for several decades

• 1.5 mg tablets used over 25 days (titration method)

• Varenicline derived from Cytisine (analogues)

• Established effectiveness for promoting smoking cessation

• Cytisine at least as effective as varenicline in supporting abstinence rates at 6 months

• Common side effects: GI problems, headaches, irritability, nausea, constipation, difficulty sleeping, tachycardia

• Contraindicated in arterial hypertension and advanced atherosclerosis

• TGA interim decision creates a Schedule 3 entry (i.e., a pharmacist-only medicine) for cytisine for divided oral and oro-mucosal preparations with a maximum of 9 mg as a smoking cessation aid for adults, and a Schedule 4 entry (i.e., prescription only) for all other preparations of Cytisine

• There are currently no TGA approved products on the market containing cytisine

Pharmacotherapy Combinations

Combinations therapy:

• Two forms of NRT

  • Patch and gum/lozenge/mouth spray

• Varenicline and NRT

• Bupropion and NRT

  • Bupropion and patch

• Varenicline and Bupropion

Nicotine vaping products in smoking cessation

There are currently no nicotine vaping products approved by the TGA and registered in Australian Register of Therapeutic Goods (ARTG)

Pharmacotherapeutic considerations

• Clinical eligibility

• Past experiences and outcomes

• Patient preferences / convenience

• Cost

• Compliance and adherence complications

Non-pharmacological Interventions

Avoid triggers

Changing routines / shifting to reinforcing alternatives

Adequate rest and relaxation

Exercise

Healthy diet

Avoiding secondhand smoke

Summary

• Smoking cessation interventions, provided by healthcare professionals can significantly increase quit rates

• Evidence based pharmacotherapy represents the cornerstone of smoking cessation interventions

• Clinical eligibility, previous therapy, patient preference, convenience and cost are essential criteria for guiding the choice pharmacotherapy