Week 6 - Nicotine Flashcards
What is nicotine?
comes from the plant form nicotiana tabacum
- smoking tobacco
- smokeless tobacco
Inhalation of nicotine
smoking
- nicotine in smoke and ash
- 90% absorbed through the mucous membrane in the lungs
- directly to the heart and reaches the brain in ~ 7 seconds
- amount absorbed is determined by how a cigarette is smoked and volume of smoke
- some nicotine is absorbed through the mouth
Inhalation of nicotine
snuff
most nicotine absorbed through nasal cavity membrane
Inhalation of nicotine
nasal spray
most similar to smoking route of administration and absorption
Inhalation of nicotine
electronic nicotine delivery system (ENDS)
similar to smoking (vapours absorbed in lungs), but variable (many factors)
Oral administration
chewing
tobacco absorbed through mouth membranes
Oral administration
ingestion
- tobacco rarely swallowed
- poorly absorbed
- most metabolised via liver
- usually induces vomiting
Oral administration
nicotine gum
- nicotine levels rise and fall with chewing
- peak approx 1/3 that of smoking
transdermal administration
patches
- slow build up of nicotine
- constant level of nicotine mainted for hours
distribution
- depends on route of administration and time of administration
- nicotine leaves the brain ~30 min and concentrates in the liver kidneys, salivary glands and stomach
- nicotine crosses most barriers and is found in sweat, saliva, breast milk and placenta
Excretion
Kidneys:
- depends on pH i.e. 30-40% excreted if pH<7
Liver:
- Metabolised to cotinine (~80%), nicotine-1-N-oxide
- half-life ~90-150 mins in adults
- minimal day-to-day accumulation
- metabolism depends on gender, smoker vs non-smoker, genetics (CYP2A6 gene)
physiological effects of nicotine
- increased heart rate
- increased blood pressure
- vasoconstriction in skin (skin temperature, cold touch, aging/wrinkles, blushing)
- inhibits stomach secretion
- stimutes bowel activity - laxative effect
2 types of cholinergic receptor sites
Mucarinic: stimulated by muscarine; blocked by atropine
Nicotinic (NacHr): mainly ionotropic, stimulated by nicotine and blocked by curate (neuromuscular), mecamylamine (neuronal)
3 main configurations of nicotonic
- Basal state: closed ion channel at rest; high affinity for antagonists
- Active state: open channel; low affinity for agonist & antagonists
- Desensitised state: closed channel; insenesitive to agonists/antagonists
dosage effect on receptors
low doses: nicotine stimulates nicotinic cholinergic receptors
high doses: blocks nicotinic cholinergic receptors
nicotonic receptors in synapses of the brain
use dopamine and noradrenalin and release when stimulated
- nicotine also releases serotonin, beta-endorphine and hormones
Nicotine and the PNS
- nicotonic receptor sites located at neuromuscular junctions of striated muscles
- nicotine stimulation = muscles tremors
- nicotine causes release many neurotransmitters that affect the PNS e.g. adrenaline/epinephrine
Nicotine and the CNS
- direct effect on synapses
- release of adrenalin from various sites (synapses and adrenal glands)
- stimulation of reticular activating system
- all result in increased arousal
neurophysiological effects of nicotine
- stimulation of medulla - increased respiration
- inhibition of reflexes due to stimulation of inhibitory cells in spinal cord
- vomiting centre also stimulated
- release of norepinephrine and dopamine & stimulation of systems that use these neurotransmitters
- serotonin systems also affected - antidepressant action
effects on mood
subjective effects
- acute effects - pleasurable (by smokers)
- chronic effects - stress, well being ratings
effects on sleep
- I.V. nicotine - REM sleep in cats but not humans
- withdrawal may affect sleep (increased REM)
effects on performance
depends on:
- smokers vs non-smokers
- withdrawal
General effects:
- increased speed and accuracy of vigilance, attention & information processing (only on ST)
- faster motor reaction time e.g. finger tapping speed
effects on cognitive functioning
- effects of smoking similar to arousal - thus has effect on learning
- immediate recall impaired, but later recall improved
- alzheimer’s disease
- contentious area of research: many other studies show null or negative effects of nicotine on cog function
animal studies
spontaneous motor activity in rats usually depressed intially but increases after 7 days
- initial SMA due to increase ACh - then tolerance
- increased adrenalin produces SMA similar to amphetamines
conditioned responses
nicotine & amphetamine effects on conditioned behaviour are similar
- slows high rates of behaviour and increases low rates of behaviour
- does not increase punished responses
- withdrawl can disrupt shock-avoidance behaviour
may be due to catecholamine release associated with nicotine
self-administration
animals
- most animals do not self-administer
- reinforcement depends on forced consumption, paired stimuli, reinforcement schedules which impose abstinence between administration
- nicotine can also serve as a punisher
self-administration
humans
- reinforcing in humans
- self-administration is less frequent with higher doses & more frequent with lower doses
theories for higher self-administration with lower doses
- maintain constant nicotine level
- trying to achieve high doses
- situation & expectations
- dual reinforcement model
discriminative properties
- 0.2mg/kg can be successfully discriminated - does not generalise to adrenalin, pentobarbital , caffeine
- may partially generalise to amphetamines and cocaine
- low doses of ethanol blocks nicotine discrimination in rats but not humans
- humans can discriminate different doses
tolerance
develops to nausea produced by stimulating the vomit centre of the brain
withdrawal symptoms
- decreased heart rate
- excessive eating
- lower levels of concentration
- distrubed sleep
- cravings
- anxiety
- depression
- agression
- headaches
- nausea
withdrawal
- develops over 1st 3 days of abstinence, peak at ~1wk then decreases
- most symptoms disappear >1 month; cravings may persist and triggered by cue exposure
- severity not related to dose, length of smoking, previous attempts to quit, age, gender, alcohol or caffeine
- fast metabolisers: more severe withdrawal
treatment
- 2/3 adult smokers want to quit; only 1/10 attempters succeed
- nicotine replacement therapy includes patches gum and nasal spray
- pharmacotherapies include buproprion (Zyban) and varenicline (champix)
- future is looking at nicotine vax
