Drugs of abuse: Nicotine and Alcohol (Prof. Millar) Flashcards
How many chamicals make up tobacco smoke ?
Which one is responsible for its addictive and important pharmacological effects ?
About 4000.
Nicotine.
How long does it take for inhaled nicotine to reach the brain ?
How long does it take for the effects of nicotine to dissipate ?
Inhaled nicotine is absorbed into the bloodstream via the lungs and rapidly distributed throughout the body, reaching the brain within approx 10 seconds.
The effects of nicotine dissipate w/in a few minutes:
- an initial rapid fall due to redistribution between blood and other tissues (20mins)
- a slower decline due to oxidative metabolism in the liver (to cotinine) (30-100min)
Where are ionotropic nAChRs found ?
- NMJ
- Autonomic ganglia (in the sympathetic & parasympathetic NS)
- CNS
How many subunits make up the nAChR ?
5 (pentameric) –> α, β, γ, δ, ε
Which nAChR subunits have been implicated in mediating the addictive effects of nicotine ?
Why ?
The α4 and β2 subunits.
Self-administration of nicotine is attenuated in mice containing a deletion of the gene encoding the nAChR β2 subunit. [Picciotto et al. (1998) Nature 391, 173-177]
Where are nAChRs located at the NMJ ?
In the CNS and PNS ?
NMJ = post-synaptic CNS/PNS = pre- and post-synaptic
What effect does nicotine on other NTs ?
Nicotine stimulates the release of several NTs including: DA, NA, GABA, endorphins DA ⇒ psychoactive effects NA ⇒ increased attentiveness GABA and endorphins ⇒ anxiolytic effects
In which regions of the brain does nicotine stimulate DA release ?
Nicotine activates nAChRs in the brain causing
the release of DA in the mesolimbic DA pathway (or “reward centre”).
What are the three main areas of the mesolimbic pathway ?
VTA –> nucleus accumbens –> cerebral cortex
VTA (just above brainstem) = DA releasing neurons
Nucleus accumbens = relay messages about pleasure coming from the VTA and going to cerebral cortex
Cerebral cortex = where the message arrives
There are also reciprocal connections between the VTA and the tegmental pedunclopontine nucleus (TPP).
What are the effects of nicotine of the ANS ?
Mixture of sympathetic and parasympathetic effects:
- Increased heart rate
- Increased blood pressure
- Increased sweating
- Decreased gastrointestinal motility
- Release of AD and NA from adrenal medulla
What are the effects of nicotine on the CNS ?
Stimulatory and inhibitory effects:
- symptoms of stimulation and arousal
- can also alleviate stress and anxiety
- may enhance learning and sensory performance
What are the effects of nicotine on sk muscle ?
Relaxation (due to activation of nAChRs in spinal cord, rather than direct effect at NMJ)
What other negative effects can nicotine have ?
- Tolerance (higher doses required to produce the same effect)
- Physical withdrawal symptoms (days-weeks): irritability, restlessness, attentional deficits, sleep disturbances, hunger
- Craving (can persist for much longer)
How much does 1 unit of alcohol raise blood alcohol ?
15mg/100ml.
How fast do we metabolise alcohol ?
~15mg/100ml per hour (~1 unit/hour)