Overview of electronic cigarettes including history, components, safety and adverse events, efficacy in smoking cessation, pharmacokinetics and epidemiology. This presentation was originally delivered to 2nd year pharmacy students as part of a two semester class on pharmacology and toxicology.
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
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.
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.
Editor's Notes
Image from NY Times: http://www.nytimes.com/2013/06/13/business/e-cigarettes-are-in-vogue-and-at-a-crossroads.html?pagewanted=all&_r=0
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.
From 2010-2012: 35 cases of various ages involving leaky cartridges, swallowing cartridge, using cartridge as eye-drop!
E-Cig Ad (but accurate?).
Sample was adults age 18 to 65. More research with vulnerable populations (elderly, asthma?).
“Nicorrette inhalator”
“Nicorrette inhalator”
Tested the “Categoria” e-Cig. No incentive for study participation.
Tested the “Categoria” e-Cig. No incentive for study participation.
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).
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.
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.”