Lecture 12 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Focus is on pharmacokinetics, pharmacodynamics, epidemiology, and health risks
5. Nicotine by Route of Administration
Blood nicotine after smoking 1.33 cigarettes for 9 minutes (upper left) or 2.5 g oral snuff
(upper right), 7.9 g chewing tobacco (lower left), two-2 mg pieces of nicotine gum for 30
minutes Hukkanen et al. (2005) Pharmacology Reviews, 57, 79-115.
6. Nicotine over 24 hours
• Cotinine > Nicotine
• Steady state during
day
Benowitz et al. (1983). Circadian blood concentrations of nicotine and cotinine
during unrestricted smoking. Clin Pharmacol Ther , 34, 604-611.
7. CH3 O
| ||
CH3 – N - CH2 - CH2 – O – C - CH3
Acetylcholine |
CH3
• Vagusstoff: Otto Loewi
• Function: movement
• Nicotinic ACh receptor
• Curare = nACh
antagonist
For more details, see: http://faculty.washington.edu/chudler/chnt1.html
8. Nicotine & Cognition
Nicotine was administered either 20 minutes before sample (A), just after sample (B), or
20 minutes before choice (C).
Picture from Ennaceur, Figure adapted from Puma et al. (1999) Eur J Neuropsychopharm, 9, 323-327.
9. Smoking increases nACh
• Smoking increases receptor
levels in human post-mortem
tissue in hippocampus (top)
and thalamus (bottom).
Breese et al. (1997). JPET, 282, 7-13. Non-Sm Smoker Ex-smoker
10. Smoking & MAO
• Monoamine oxidase is an
enzyme that breaks down 5-
HT and NE.
• Whole body PET scan of
humans with [11C]deprenyl in
smokers and non-smokers
reveals differences.
• Self-medication?
Red = high MAO
Fowler et al. (2003) Proceedings of the National Academy of Sciences, 100, 11600-11605.
11. Statistics
• There are three types of lies: lies, damn lies,
and statistics (Leonard Courtney)
• Absolute Risk: Rate of condition/total
population studied
• Relative Risk: Rate of condition among
exposed divided by rate of condition among
unexposed (aka Odd’s Ratio)
see Statistics_Primer.ppt for additional information
12. Example: Smoking & Lung-Cancer
Non-Smokers Smokers
Death from Lung-Cancer 10 100
Non-Death from 999,990 999,900
Lung-Cancer
Total 100,000 100,000
Absolute Risk of Non-Death: Smokers: 99.990%
Non-Smokes: 99.999%
Relative Risk: Smokers Odds of Lung Cancer Death 100/100,000 or .001
Non-Smokers Odds of Lung Cancer Death of 10/100,000 or .0001
13. Example: Smoking & Lung-Cancer
Non-Smokers Smokers
Death from Lung-Cancer 10 100
Non-Death from 999,990 999,900
Lung-Cancer
Total 100,000 100,000
Absolute Risk of Non-Death: Smokers: 99.990%
Non-Smokes: 99.999%
Relative Risk: Smokers Odds of Lung Cancer Death 100/100,000 or .001
Non-Smokers Odds of Lung Cancer Death of 10/100,000 or .0001
.001/.0001 = 10 Fold!
14. Fig 1 Survival from age 60 for continuing cigarette smokers and lifelong non-smokers among UK
male doctors born 1851-1899 (median 1889) and 1900-1930 (median 1915), with percentages alive
at each decade of age
Sir Richard Doll
Doll, R. et al. BMJ 2004;328:1519
1912-2005
16. Epidemiology: Who will smoke
more?
• 1) 1970s versus today?
• 2) Region of country?
• 3) Parental SES?
• 4) College plans?
• 5) Urban versus rural?
• 6) Males or Females?
27. No Sex Differences
Monitoring the Future
National Household
Survey on Drug Use
And Health
28. Smoking &
Pregnancy
• Risks of smoking:
– Spontaneous abortion: 26 weeks
– Small size: SGA
– SIDS: 1 month to 1 year
– Behavioral issues: ADHD
• Smoking Cessation:
– NRT PK?
NHSDUH, 2011
29. Dose Related?
• Online study with Craigslist volunteers
• Behavioral Rating of Executive Function
Piper & Corbett (2012) Nicotine & Tobacco Research, 14, 191-199.
30. Benefits of Quitting Smoking
• Hypothesis:
Smoking during
pregnancy, but not
quitting, has
negative outcomes
• Online study of
non-smokers,
smokers, quitters
Piper et al. (2012). Drug & Alcohol Dependence, 121, 62-67.
34. versus
Pfizer
GSK
• Smokers were assigned to
either nicotine replacement
(N=376) for 10 weeks (21,14,
7 mg) or Chantix (N=370) for
11 weeks.
• Most participants in both
groups (60%+) in both groups
complete the 1 year study
• Dependent measures = self-
reported abstinence
(confirmed by CO), weight
gain, adverse effects
OR = 56.9 / 43.2 = 1.70!
Aubin, Bobak, Britton, et al. (i2008). Thorax, 63, 717-724.
35. But there’s more …
>
>
Rates of Not quitting:
Varenicline = 73.9%
NRT = 79.7%
Dysgeusia: an impairment in the sense of taste
Aubin, Bobak, Britton, et al. (in press 2008). Thorax.
39. Lesions of Insula
• Smoking following brain
damage was examined in
patients with insula
damage.
Naqvi et al. (2007). Science, 315, 531-534.
40. Lesions of
Insula
• Smoking following brain damage was
examined in patients with insula damage.
• He quit because his “body forgot the urge
to smoke”
Naqvi et al. (2007). Science, 315, 531-534.
42. versus
Pfizer
GSK
• Smokers were assigned to
either nicotine replacement
(N=376) for 10 weeks (21,14,
7 mg) or Chantix (N=370) for
11 weeks.
• Most participants in both
groups (60%+) in both groups
complete the 1 year study
• Dependent measures = self-
reported abstinence
(confirmed by CO), weight
gain, adverse effects
OR = 56.9 / 43.2 = 1.70!
Aubin, Bobak, Britton, et al. (in press 2008). Thorax.
43. 4.4
But there’s more …
>
>
Rates of Not quitting:
Varenicline = 73.9%
NRT = 79.7%
Dysgeusia: an impairment in the sense of taste
Aubin, Bobak, Britton, et al. (in press 2008). Thorax.