Nicotine Flashcards
(28 cards)
How is nicotine cultivated?
dried tobacco leaves contain ~6% nicotine (active alkaloid)
What is in tobacco smoke?
nicotine, carbon monoxide and thousands of particulates (many are carcinogenic)
What are the risks of smoking?
around 1/4 cancer deaths not caused by genetic factors are attributable to smoking tobacco
half of all lifetime smokers die prematurely because of cigarette-induced disease
What factors can influence smoking?
socioeconomic; bachelor degree holders are less likely to smoke age; highest level of smoking 20-34 men smoke more than women price culture
Routes of administration
most routes are effective except for ingestion
smoking, snuff, gum, chewing tobacco
Which is the optimal route of administration for peak subjective high?
inhaling cigarette smoke allows nicotine to reach the brain in ~ 7 seconds
When can nicotine be poisonous?
~60mg is a lethal dose in humans
each cigarette contains ~6-11mg, of which 1-3mg is absorbed
What aversive symptoms can high nicotine doses cause?
nausea, dizziness, sweating, heart racing, stomach ache; potent activator of the sympathetic and parasympathetic nervous system
How can nicotine be lethal?
very high dose can cause a depolarisation block on the muscles involved in respiration
How is nicotine metabolised?
nicotine is metabolised into cotinine by the cytochrome P450 2A6 enzyme and excreted through urine
evidence; methoxsalen inhibits enzyme and creates unpleasant symptoms at lower concs
What are the subjective effects of nicotine?
relaxation
stress alleviation
concentration; sustained attention and memory
How can nicotine self-administration be modelled in rodents?
IV nicotine SA can be difficult to achieve
behaviour is strongly controlled by conditioned cues
- e.g. humans; smoke, rodents; light/sound etc.
conditioned cues are strong at low doses but not at high doses
What metabolic changes are associated with smoking?
reduction in monoamine oxidase B
What is the function of monoamine oxidases?
break down monoamine NT’s (DA and NE) into inactive metabolites
What are the implications of reduced MAO?
psychiatric disorders
lower rates of Parkinsons Disease
What evidence is there for the role of MAO in nicotine SA?
MAO inhibitors greatly facilitate nicotine SA and sensitisation
extended access + MAO inhibition = greatest escalation of nicotine SA
What are the withdrawal symptoms of nicotine addiction?
irritability, anxiety, difficulty concentrating
disappear after 4 weeks
nicotine replacement therapy can help
Where is acetylcholine found?
the neuromuscular junction
How is ACh synthesised?
choline (dietary precursor) + acetyl coenzyme A + choline acetyltransferase = acetylcholine + coenzyme A
How is ACh degraded?
Ahh + acetylcholinesterase = choline + acetic acid
What are the classes of ACh receptor?
metabotropic; muscarinic
ionotropic; nicotinic
What is the structure of nAChR?
pentameric ligand-gated cation channel
alpha and beta subunits (12 types) can combine in various ways
What is the structure of nAChR?
pentameric ligand-gated cation channel
alpha and beta subunits (12 types) can combine in various ways; usually 3a and 2b
What is the structure of mAChR?
g-protein coupled receptor that serves various functions in the CNS
