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Overview of e-Cigarettes
Brian J. Piper, Ph.D., M.S.
School of Pharmacy, Husson
University
Goals
•
•
•
•
•

What is an e-Cigarette?
History
Pharmacokinetics
Efficacy
Safety
History
• 1963: Herbert Gilbert patented steam dispensing
product
• 2003: pharmacist Hon Lik (image) invents
eCigarette dispensing nicotine
• 2004: Ruyen begins selling eCigs
• 2010: FDA decides e-Cigs are drug/delivery
devices
• 2012: Cigarette companies in US
get on board

Hon Lik
Components

Cartridge: 150-300 puffs, may contain flavors
Terminology
• vapor (n): gaseous particles of drugs
• vaping (v): process of inhaling vapor from
personal vaporizer
• vapers (n): people that use e-Cigs
Contents of Cartridge
• Majority
– propylene glycol ( > half)
– glycerin
– nicotine (various levels)
– various flavors

• Trace
– diethylene glycol (0.1% in 1/18 samples)
– tobacco specific nitrosamines
Cahn & Siegel J Public Health Policy 32 (2011) p. 22.
Tobacco Specific Nitrosamines

Cahn & Siegel J Public Health Policy 32 (2011) p. 22.
Nicotine Poisonings
• Possible in theory (>500 mg can be fatal), 100
ml refill cartridges contain 72 mg/ml
• Not common (yet?)

Cantrall J Community Health (2013) in press.
Adverse Events
• Nicotine increases heart-rate and blood
pressure.
• E-Cig adverse effects are likely due to inhaling
propylene glycol are transient in small/shortterm studies.
Adverse Events (N = 40)

Coponetto et al. Exp Rev Respir Med 2012: 6(1):63-74.
Do e-Cigs reduce craving?
• Smokers (1 ppd, age 48, N= 40) that had not
smoked for 12 hours were received electronic
nicotine delivery device (ENDD, 16 or 0 mg) or
usual cigarette
• self-report

Bullen Tobacco Control 19 (2010) 98-103.
What is the PK profile for e-Cigs
• Smokers (1 ppd, age 48, N= 40) that had not
smoked for 12 hours were received electronic
nicotine delivery device (ENDD, 16 or 0 mg) or
usual cigarette

Cigarette

e-Cigarette

Tmax (min)

14.3

19.6

Cmax (ng/ml)

13.4*

1.3
* p < .05

Bullen et al. Tobacco Control 19 (2010) 98-103.
Do e-Cigs aid smoking cessation?
Nicotine Replacement Studies

e-Cigarettes Studies

# RCTs

many

2

psychological support

high

low

participants

exclude mentally ill

naturalistic

1 year abstinence

doubled (20% vs 10%)

?
Do e-Cigs aid smoking cessation?
• Superiority trial of adults (age = 40s, 18
cig/day). Participants randomized (4:4:1) to:
– Elution e-Cig (“placebo”: 0 mg/ml nicotine)
– Elution e-Cig (16 mg/ml nicotine)
– nicotine patch (21 mg/24 hours)

Bullen et al. Lancet 382 (2013) 1629-1637.
Do e-Cigs aid smoking cessation?
e-Cig (16 mg)
(N = 289)

e-Cig (0 mg)
(N=295)

Nicotine Patch
(N=77)

use of psychological support

40%

36%

36%

use of study product at 3 months

51%

53%

18%

drop-out of study

17%

27%

22%

smoking abstinence at 6 months
days to relapse
recommend product to friend

Bullen et al. Lancet 382 (2013) 1629-1637.
Do e-Cigs aid smoking cessation?
e-Cig (16 mg)
(N = 289)

e-Cig (0 mg)
(N=295)

Nicotine Patch
(N=77)

use of psychological support

40%

36%

36%

use of study product at 3 months

51%

53%

18%

drop-out of study

17%

27%

22%

smoking abstinence at 6 months

7.3%

5.8%

4.1%

days to relapse

35

12

14

recommend product to friend

85%

88%

50%

Bullen et al. Lancet 382 (2013) 1629-1637.
Do e-Cigs aid in smoking reduction?
• Smokers (N = 300), not planning to
quit, randomized to:

Caponotto et al. (2013) PLoS One 8(6): e66317.
Do e-Cigs aid in smoking reduction?
• Study completion rates:
– A (7.2/7.2 nic): 65%
– B (7.2/5.4 nic): 63%
– C (0 nic): 55%

Caponotto et al. (2013) PLoS One 8(6): e66317.
Do e-Cigs aid in smoking reduction?
• One-year smoking cessation rates (not significant but … )
– A (7.2/7.2 nic): 13%
– B (7.2/5.4 nic): 9%
– C (0 nic): 4%

Caponotto et al. (2013) PLoS One 8(6): e66317.
Free Advertising?
Center’s for Disease Control (2013). Morbidity Mortality Weekly Report 62(35), 729-730.
Comparison
Pros

Cons

Less adverse health consequences

Renormalizing taboo behavior; longterm safety of inhaled propylene glycol
vapor?

No second-hand smoke

Second-hand mist contains nicotine

Pharmacokinetics mimics smoking

Requires practice

Replicates motor pattern of smoking

Heavier than cigarette

Relieves withdrawal and craving

Reinforcing/addictive

Cleaner

Disposal of cartridge and batteries, some
flavors linger in air

Readily available

Limited quality control on nicotine
concentration. Contaminants?

Modified from Polosa et al. Harm Reduction Journal 10: 19.
Summary
• E-cigs, relative to traditional cigarettes, have the
potential for substantial harm reduction.
• Based on limited and short-term evidence,
adverse effects appear minimal. Inconsistency in
manufacture is a concern. Each e-cig make/model
is different.
• E-cigs appear as (in)effective as NRT in smoking
cessation.
• 1.8 million middle-and high-school students in
U.S. tried e-Cigs in 2012.
Ethical, Legal Questions+
• What limitations on sales (18, 21?) are warranted?
• Should bans on smoking in public places, outdoor
and indoor, also apply to e-Cigs?
• Should restrictions on advertising (e.g. movies)
also apply to e-Cigs?
• How will they be taxed?
• What is the safety of e-Cigs during pregnancy?
• What other drugs (THC, morphine) can be
administered using this technology?
Key References
• C Bullen, H McRobbie, S Thornley, M Glover, R Rin, & M Lausgen, Effect of an
electronic nicotine delivery device (e cigarette) on desire to smoke and
withdrawal, user preferences, and nicotine delivery: Randomized cross-over
trial. Tobacco Control 19 (2010) 98-103.
• Z Cahn, M Siegel, Electronic cigarette as a harm reduction strategy for tobacco
control: A step forward or a repeat of past mistakes. J Public Health Policy 32
(2011) 16-31.
• FL Cantrall, Adverse effects of e-Cigarette exposures. J Community Health
(2013) in press.

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electronic cigarettes

  • 1. Overview of e-Cigarettes Brian J. Piper, Ph.D., M.S. School of Pharmacy, Husson University
  • 2. Goals • • • • • What is an e-Cigarette? History Pharmacokinetics Efficacy Safety
  • 3. History • 1963: Herbert Gilbert patented steam dispensing product • 2003: pharmacist Hon Lik (image) invents eCigarette dispensing nicotine • 2004: Ruyen begins selling eCigs • 2010: FDA decides e-Cigs are drug/delivery devices • 2012: Cigarette companies in US get on board Hon Lik
  • 4.
  • 6. Terminology • vapor (n): gaseous particles of drugs • vaping (v): process of inhaling vapor from personal vaporizer • vapers (n): people that use e-Cigs
  • 7. Contents of Cartridge • Majority – propylene glycol ( > half) – glycerin – nicotine (various levels) – various flavors • Trace – diethylene glycol (0.1% in 1/18 samples) – tobacco specific nitrosamines Cahn & Siegel J Public Health Policy 32 (2011) p. 22.
  • 8. Tobacco Specific Nitrosamines Cahn & Siegel J Public Health Policy 32 (2011) p. 22.
  • 9. Nicotine Poisonings • Possible in theory (>500 mg can be fatal), 100 ml refill cartridges contain 72 mg/ml • Not common (yet?) Cantrall J Community Health (2013) in press.
  • 10.
  • 11. Adverse Events • Nicotine increases heart-rate and blood pressure. • E-Cig adverse effects are likely due to inhaling propylene glycol are transient in small/shortterm studies.
  • 12. Adverse Events (N = 40) Coponetto et al. Exp Rev Respir Med 2012: 6(1):63-74.
  • 13. Do e-Cigs reduce craving? • Smokers (1 ppd, age 48, N= 40) that had not smoked for 12 hours were received electronic nicotine delivery device (ENDD, 16 or 0 mg) or usual cigarette • self-report Bullen Tobacco Control 19 (2010) 98-103.
  • 14. What is the PK profile for e-Cigs • Smokers (1 ppd, age 48, N= 40) that had not smoked for 12 hours were received electronic nicotine delivery device (ENDD, 16 or 0 mg) or usual cigarette Cigarette e-Cigarette Tmax (min) 14.3 19.6 Cmax (ng/ml) 13.4* 1.3 * p < .05 Bullen et al. Tobacco Control 19 (2010) 98-103.
  • 15. Do e-Cigs aid smoking cessation? Nicotine Replacement Studies e-Cigarettes Studies # RCTs many 2 psychological support high low participants exclude mentally ill naturalistic 1 year abstinence doubled (20% vs 10%) ?
  • 16. Do e-Cigs aid smoking cessation? • Superiority trial of adults (age = 40s, 18 cig/day). Participants randomized (4:4:1) to: – Elution e-Cig (“placebo”: 0 mg/ml nicotine) – Elution e-Cig (16 mg/ml nicotine) – nicotine patch (21 mg/24 hours) Bullen et al. Lancet 382 (2013) 1629-1637.
  • 17. Do e-Cigs aid smoking cessation? e-Cig (16 mg) (N = 289) e-Cig (0 mg) (N=295) Nicotine Patch (N=77) use of psychological support 40% 36% 36% use of study product at 3 months 51% 53% 18% drop-out of study 17% 27% 22% smoking abstinence at 6 months days to relapse recommend product to friend Bullen et al. Lancet 382 (2013) 1629-1637.
  • 18. Do e-Cigs aid smoking cessation? e-Cig (16 mg) (N = 289) e-Cig (0 mg) (N=295) Nicotine Patch (N=77) use of psychological support 40% 36% 36% use of study product at 3 months 51% 53% 18% drop-out of study 17% 27% 22% smoking abstinence at 6 months 7.3% 5.8% 4.1% days to relapse 35 12 14 recommend product to friend 85% 88% 50% Bullen et al. Lancet 382 (2013) 1629-1637.
  • 19. Do e-Cigs aid in smoking reduction? • Smokers (N = 300), not planning to quit, randomized to: Caponotto et al. (2013) PLoS One 8(6): e66317.
  • 20. Do e-Cigs aid in smoking reduction? • Study completion rates: – A (7.2/7.2 nic): 65% – B (7.2/5.4 nic): 63% – C (0 nic): 55% Caponotto et al. (2013) PLoS One 8(6): e66317.
  • 21. Do e-Cigs aid in smoking reduction? • One-year smoking cessation rates (not significant but … ) – A (7.2/7.2 nic): 13% – B (7.2/5.4 nic): 9% – C (0 nic): 4% Caponotto et al. (2013) PLoS One 8(6): e66317.
  • 23. Center’s for Disease Control (2013). Morbidity Mortality Weekly Report 62(35), 729-730.
  • 24. Comparison Pros Cons Less adverse health consequences Renormalizing taboo behavior; longterm safety of inhaled propylene glycol vapor? No second-hand smoke Second-hand mist contains nicotine Pharmacokinetics mimics smoking Requires practice Replicates motor pattern of smoking Heavier than cigarette Relieves withdrawal and craving Reinforcing/addictive Cleaner Disposal of cartridge and batteries, some flavors linger in air Readily available Limited quality control on nicotine concentration. Contaminants? Modified from Polosa et al. Harm Reduction Journal 10: 19.
  • 25. Summary • E-cigs, relative to traditional cigarettes, have the potential for substantial harm reduction. • Based on limited and short-term evidence, adverse effects appear minimal. Inconsistency in manufacture is a concern. Each e-cig make/model is different. • E-cigs appear as (in)effective as NRT in smoking cessation. • 1.8 million middle-and high-school students in U.S. tried e-Cigs in 2012.
  • 26. Ethical, Legal Questions+ • What limitations on sales (18, 21?) are warranted? • Should bans on smoking in public places, outdoor and indoor, also apply to e-Cigs? • Should restrictions on advertising (e.g. movies) also apply to e-Cigs? • How will they be taxed? • What is the safety of e-Cigs during pregnancy? • What other drugs (THC, morphine) can be administered using this technology?
  • 27. Key References • C Bullen, H McRobbie, S Thornley, M Glover, R Rin, & M Lausgen, Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences, and nicotine delivery: Randomized cross-over trial. Tobacco Control 19 (2010) 98-103. • Z Cahn, M Siegel, Electronic cigarette as a harm reduction strategy for tobacco control: A step forward or a repeat of past mistakes. J Public Health Policy 32 (2011) 16-31. • FL Cantrall, Adverse effects of e-Cigarette exposures. J Community Health (2013) in press.

Notas do Editor

  1. Image from NY Times: http://www.nytimes.com/2013/06/13/business/e-cigarettes-are-in-vogue-and-at-a-crossroads.html?pagewanted=all&amp;_r=0
  2. Source: http://www.nytimes.com/2013/06/13/business/e-cigarettes-are-in-vogue-and-at-a-crossroads.html?pagewanted=all&amp;_r=0
  3. Source: http://rodutobaccotruth.blogspot.com/2012/12/the-e-cigarette-revolution.html
  4. Mint and fruit flavors are common
  5. Glycerin is sugar alcohol used in a wider variety of preparations. 15 other studies looked for diethylene glycol and did NOT find it. Monoethylene glycol is a component of antifreeze. Fruit, mint, and candy flavors.
  6. From 2010-2012: 35 cases of various ages involving leaky cartridges, swallowing cartridge, using cartridge as eye-drop!
  7. E-Cig Ad (but accurate?).
  8. Sample was adults age 18 to 65. More research with vulnerable populations (elderly, asthma?).
  9. “Nicorrette inhalator”
  10. “Nicorrette inhalator”
  11. Tested the “Categoria” e-Cig. No incentive for study participation.
  12. Tested the “Categoria” e-Cig. No incentive for study participation.
  13. Tested the “Categoria” e-Cig. This was an early model, common when the study started, but has since been discontinued. No incentive for study participation. Only 1/3rd of people that quit were still using eCigs at week 52 (no transfer of addiction).
  14. NYTS is nationally representative sample of all students in U.S. Lifetime use doubled. Current use (past month) went from 0.6 to 1.1! 61% of e-Cig users are current smokers of conventional cigarettes.
  15. As of Sept 6, 2013: “Twelve states have laws preventing e-cigarette sales to minors - California, Colorado, Idaho, Iowa, Maryland, Minnesota, New Jersey, New Hampshire, New York, Tennessee, Utah and Wisconsin. New York banned e-cigarette smoking within 100 feet of an entrance to a public or private school.”