Nicotine

Question 1

history and botany of tobacco

Answer 1

a member of solanaceae family, originating from central and south america.

evidence of use from 12300 year ago through indigenous peoples.

australia also has indigenous tobacco

was brought to iberia (spain) in the 1520s and samples sent to paris and england in 1559 and 1570.

from the late 1600s, extracts were used as insecticides.

nicotine was isolated in 1828 in germany

Question 2

Cycle of consumption

Answer 2

the first use is marked by aversion and reinforcement.

subsequent uses see a reduction in aversion through use-induced plasticity.

reinforcement conditions continued use and abstinence prompts withdrawals - promotes relapse. this cycle is smaller the more addicted an individual is

Question 3

Molecular and cellular effects

Answer 3

direct activation of nAChRs, except a9-a10 subunits where it is an antagonist - potentially explains mild analgesic effects

increases VTA and NAc dopamine release (through a4B2 subunits), reinforcing and rewarding the behaviour. Also increases monoamine (particularly DA) release in medial habenula/interpeduncular nucleus pathway

repeated use sees a4B2 upregulation in cerebral cortex and B3 and B4 upregulation in medial habenula/interpeduncular nucleus.

stimulation of nAChR in sympathetic ganglia increases NA and adrenaline release leading to vasoconstriction. higher doses can cause hypotension and circulatory collapse through ganglionic blockade

Question 4

PK of nicotine

Answer 4

higher absorption in the lungs than in the mouth. depth of inhalation also affects amount absorbed. can cross the skin (transdermal patches)

has very rapid BBB penetration 10-20 seconds.

can alter CYP450 metabolism through induction following long term use

Question 5

Changes in the attitudes to smoking

Answer 5

tobacco flooded europe in the mid 1600s. was promoted to protect against the black plague.

prussia banned smoking in public in 1840

smoking was banned in 15 US states in 1890. ban later removed.

WW1 saw a massive increase in smoking - idea of “soldier’s smokes”.

Hitler banned public tobacco consumption in germany in 1941 following an anti-smoking campaign since coming to power.

WW2 saw the peak of smoking rates, and then in 1952 the carcinogenicity of smoking was first identified.

Question 6

Statistics of smoking

Answer 6

1.14b smoked in 2019.

1 smoking related death per 0.8-1.1m cigarettes

asia and eastern europe see the highest rates of smoking related mortality. Greenland sees the highest of any country. significant proportion of these countries see disability-adjusted life year - the equivalent of a loss of one year of life

chewing tobacco sees reduced toxicity to smoking

there is a trend of decreasing numbers of smokers and increasing number of people who have never smoked

Vaping has seen a massive resurgence in young users of nicotine - people who would not necessarily smoke tobacco