Smoking

• Smoking is a major cause of preventable morbidity and mortality in the developed world
• In Australia, 11.1% of adults aged ≥18 years are daily smokers, resulting in 18,000 deaths annually and $32 billion in health, social and economic costs
• Smoking accounts for 9% of the total burden of disease and injury in Australia, and 25% of cancer and 90% of COPD cases
• Smoking contributes to the death of one-third to one-half of all lifetime users, killing more than AIDS, legal drugs, illegal drugs, road accidents, murder and suicide combined
• Nicotine dependence


  A chronic condition characterised by remission and relapse, and hard to cure
• Nicotine dependence


  • Development of behavioural, cognitive and physiological phenomena, including a strong desire to smoke, use of tobacco despite medical and social detriments, persisting use despite harmful consequences, need for increased doses of nicotine to obtain the same pleasurable effects, and withdrawal state when tobacco use is reduced or ceased
• Nicotine dependence (DSM-V)


  Classified as 'tobacco use disorder', with the presence of at least 2 of the following criteria: impaired control, social impairment, risky use, and pharmacologic dependence
• Nicotine is the most addictive but not the most harmful substance in a cigarette
• Pharmacokinetics of nicotine


  Colourless and odourless naturally occurring alkaloid, with a short half-life of 40-120 minutes and a whole life up to 20 hours
• Nicotine plasma concentration


  Range of 10-80 ng/ml, with a range of 20-35 ng/ml for regular smokers

  
• Nicotine metabolism


  Mainly metabolised by CYP2A6, with other enzymes like CYP2B6, CYP2E1 and CYP1A2 also involved; cotinine is nicotine's major non-addictive metabolite

  
• Smoking induces CYP1A2 and CYP2B6, leading to major tobacco-associated drug interactions
• Pathophysiology of nicotine dependence


  1. Absorption of nicotine by the respiratory tract, rapid absorption into the pulmonary venous circulation, reaching the brain in less than 10-20 seconds

  2. Activation of dopaminergic receptors and release of rewarding neurotransmitters, leading to pleasurable effects

  3. Desensitisation and upregulation of receptors with chronic exposure, resulting in tolerance and dependence

  4. Withdrawal symptoms upon reduction or abstinence, including increased noradrenergic outflow and a strong tendency to relapse post quitting

  
• Cigarette smoke contains over 4,000 toxins, including more than 40 clinically proven carcinogens, and hundreds of additives and flavourings, with detrimental effects on vital organs, the immune system, and key body functions, ultimately reducing life expectancy
• Benefits of smoking cessation


  • Improved lung function, reduced risk of heart attack and lung cancer, and decreased risk of miscarriage, preterm delivery, low birth weight baby and sudden infant death syndrome
• Role of pharmacists in smoking cessation


  1. Applying the 5As (Ask, Advise, Assess, Assist, Arrange) and the 5Rs (Relevance, Risks, Rewards, Roadblocks, Repetition) to support patients in quitting smoking

  2. Assessing nicotine dependence using tools like the Fagerström test and Heaviness of Smoking Index, and the patient's willingness to change using the Stages of Change model

  3. Providing pharmacological interventions, including nicotine replacement therapy, varenicline, bupropion, and other options
• Nicotine replacement therapy


  Safe and effective options, including gums, lozenges, inhalators, transdermal patches, mouth sprays, and nasal sprays (not available in Australia), with precautions, contraindications, and potential adverse effects
• Smoking cessation pharmacotherapies


  • Varenicline
  • Bupropion
  • Nortriptyline
  • Clonidine
  • Naltrexone
• Nicotine Replacement Therapy (NRT)


  Nicotine-containing products that provide a safer alternative to smoking
• Precautions/Contraindications for NRT


  • Recent heart attack within the past 48 hours
  • Allergy to any NRT components
  • Generalised skin disorders such as sun burn or broken skin
  • Phenylketonuria
  • Menthol sensitivity
• Adverse Effects of NRT


  • Skin rashes on site of application
  • Sleep disturbances
  • Vivid dreams
  • Irritation of mouth or throat
  • Headaches
  • Dizziness
  • Hiccups
  • Indigestion
  • Nausea
  • Coughing
  • Tingling of lips
• Benefits of NRT


  • Slow delivery of lower doses of nicotine as compared to a cigarette
  • Decrease in the intensity of cravings and withdrawal symptoms
  • Reduction in the reinforcing effects of tobacco-delivered nicotine
  • Minimal addictive potential
  • Absence of toxic chemicals in cigarettes
  • Double successful quit rates as compared to placebo
  • 50-70% increase in the rate of long-term quitting
• Dosage Forms of NRT


  • 2 & 4 mg gum
  • 2 & 4 mg lozenge
  • 1.5 & 4 mg mini lozenge
  • 15 mg inhalator
  • 21, 14 & 7 mg 24-hour patch
  • 25, 15, 10 mg 16-hour patch
  • 1 mg/spray quickmist
• Nicotine delivery effects of NRT (in decreasing order)


  • Cigarette
  • Spray
  • Inhalator
  • Lozenge/Mini lozenge/Gum
  • Patch

  
• Smoking while on NRT is NOT contraindicated
• Instructions for Use - Gum


  1. Chew 1 piece of gum slowly, until flavour becomes strong or a slight peppery tingling sensation is felt

  2. Park between the cheek and gum

  3. Chew again when flavour fades

  4. Repeat until there is no more tingling or for about 30 minutes
• Instructions for Use - Lozenge


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

  2. Stop sucking until taste fades, resting the lozenge against the cheek

  3. Continue to suck again when taste fades

  4. Move lozenge occasionally from side to side

  5. Repeat until lozenge has completely dissolved
• Instructions for Use - Inhalator


  1. Insert cartridge into mouthpiece

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

  3. Continue for up to 20 minutes

  4. Replace cartridge
• Instructions for Use - Mouth Spray


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

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

  3. For best results, avoid swallowing for a few seconds after spraying
• Instructions for Use - Patch


  1. Apply the patch in the morning or bedtime

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

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

  4. Rotate site each day

  5. Do not cut patches in half

  6. Swimming and bathing are allowed 1 hour post-application
• Combination therapy (long-acting NRT + rapid-acting NRT) is more effective than monotherapy
• Combination therapy (double NRT) doubles successful quit rates
• Combination therapy (NRT + Varenicline or NRT + Bupropion) is established as safe
• Varenicline is the first line pharmacotherapy for smoking cessation
• Varenicline


  • Partial agonist acting centrally on α4β2 nicotine receptors, stimulating 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
• Precautions/Contraindications for Varenicline


  • Caution 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 to lack of conclusive evidence
  • Contraindicated in hypersensitivity to any ingredient
• Adverse Effects of Varenicline


  • Mild to moderate nausea in 30% of patients, generally diminishing with time
  • Headache
  • Insomnia
  • Vivid dreams
  • Reports of serious neuropsychiatric symptoms and suicidal ideations
• Benefits of Varenicline


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


  • 0.5 (white) & 1 mg (blue) oral tablets per pack
  • Day1-3: 0.5 mg daily
  • Day4-7: 0.5 mg twice daily
  • Day 8-week 12: 1 mg twice daily
• TGA advised about very low levels of the N-nitrosovarenicline in Australian varenicline products