Nicotine & Alcohol Flashcards
How many people smoke tobacco?
How many deaths does it cause?
How does nicotine enter the lungs by smoking?
What is significant about its absorbance?
How long is nicotine’s half life?
How is it metabolised?
1 billion
5 million a year / 13,500 a day
On tar particles - mixture of hydrocarbons (carcinogenic)
Readily passes through absorbant surface lungs - absorbed less readily when chewed or snorted
2 hours
By CYP2A6 in the liver into cotinine metabolites - which are then excreted via urine
What were the conclusions of Doll et al (2004)’s 50-year epidemiological study? 3
How quickly does nicotine reach the brain?
How quickly do the effects of nicotine dissipate and why?
To what receptors does nicotine bind & where are they found?
- Individuals who smoke continuously die 10 years younger
- Cessation at age 50 halves risk of premature death
- Cessation at age 30 ALMOST removes increased risk
7-10 seconds
Few minutes - initial rapid increase due to rapid redistribution between blood & tissues & then decline due to CYP2A6 metabolism
nAChRs - neuromuscular junctions, autonomic ganglia (sympathetic & parasympathetic nervous system) & CNS
What is the sympathetic nervous system & where does it originate?
What is the parasympathetic nervous system?
How is nicotine delivered to the brain?
What effect does nicotine have on nAChRs?
What is their structure?
Fight-or-flight response - starts in spinal cord to activate sympathetic ganglia (relay between neurones) which send signals to heart, lungs, liver, digestive system, glands etc
Rest & digest to conserve energy (decreased heart rate, vasodilation)
Pulsatile method - initial burst/increase & then periods of small increases for accumulation in the brain
Selective agonist - activates them for increased conduction of Na+ into cell & excitation
Pentameric (subunits) - varying in subunit type for diversity & sensitivity to different agonists/antagonists
What nAChR composition has a higher affinity for nicotine?
Where are high affinity nAChRs found in the CNS?
Where are they found peripherally?
What is the structure of the nAChRs found on pre-synaptic terminals & what do they release?
What nAChR subunits mediate addictive effects?
What are the 2 types of nAChRs and where are they found?
2 x a4 or a3 subunits and 3 x ß subunits
cerebral cortex, hippocampus, VTA, substantia nigra
Ganglia - of parasympathetic nervous system
a7 subunits to enhance neurotransmitter release - dopamine
a4 & ß2
Muscle - skeletal neuromuscular junctions (postsynaptic)
Neuronal - CNS & PNS (pre & post synaptic)
What are the 4 neurotransmitters that can be released from nAChRs & what effects do they produce?
How is the mesolimbic dopamine/reward pathway activated?
dopamine - psychoactive effects (induces pleasure, increased stimulation/arousal & mood modulation/stress relief)
noradrenaline - increased attentiveness/alertness
GABA & endorphins (mu opioid receptors) - both inhibitory receptors - anxiolytic effects
- Nicotine binds to nAChR in the brain stimulating neurones in the VTA to release dopamine
- Relays signal of pleasure to neurones in nucleus accumbens
- Nerve cells
What are the 4 neurotransmitters that can be released from nAChRs & what effects do they produce?
How is the mesolimbic dopamine/reward pathway activated? 3 steps
Where are there reciprocal connections?
dopamine - psychoactive effects (induces pleasure, increased stimulation/arousal & mood modulation/stress relief)
noradrenaline - increased attentiveness/alertness
GABA & endorphins (mu opioid receptors) - both inhibitory receptors - anxiolytic effects
- Nicotine binds to nAChR in the brain stimulating neurones in the VTA to release dopamine
- Relays signal of pleasure to neurones in nucleus accumbens
- Neurones signal to the prefrontal cortex
(dopamine projections)
Between VTA & tegmental pedunclopontine nucleus TPP
What are the physiological effects caused by nicotine in the autonomic/PNS? 6
What are the physiological effects caused by nicotine in the CNS? 3
What are the physiological effects caused by nicotine in skeletal muscle? 3
Increased heart rate, blood pressure, sweating, decreased gastrointestinal motility (mixture of para & sympathetic effects) release of adrenaline/noradrenaline from adrenal medulla
Stimulation & arousal, alleviate stress & anxiety, enhance learning/sensory performance
Relaxation of skeletal muscle caused by activation of nAChRs in spinal cord - nAChRs are NMJs not very sensitive to agonists
How does nicotine enhance cognitive function?
How can this be affected though?
What did Poltavski and Petros (2006) test & conclude?
What are the withdrawal symptoms of nicotine? 5
How long is the duration of withdrawal & craving?
What types of therapies are in use?
What is bupropin?
What is varenicline?
ACh role in cognitive function, memory & attention - such that their activation has positive influence on cognitive & motor performance
Enhancement also due to alleviated mood
Non-smoking students pre-screened for baseline levels of attention - subjected to Conners’ Continuous Performance Test CPT & a nicotine patch - showing that nicotine treatment increased the score as increases cognitive function in low-attention people (not high-attention group)
Irritability, restlessness, attentional deficits, sleep disturbance & hunger
Withdrawal days-weeks, craving weeks-months
Nicotine replacement therapy with patches, gums, inhalers - with lower levels of nicotine & avoiding carcinogens (better than smoking), relieves withdrawal symptoms
Smoking cessation therapy - antidepressant that involves effects on noradrenaline/dopamine transmission
Partial agonist of a4ß2 (addictive) nAChRs causing moderate/sustained increase in mesolimbic dopamine levels without nicotine & may reduce rewarding properties of nicotine in relapse
How much is 1 UK unit?
How much does 1 UK unit increase blood alcohol concentration by?
At what rate is alcohol metabolised?
What are the effects for the following alcohol blood concentrations:
- <30-50
- 50
- 80
- 60-200
- 200-300
- 300-400
- > 400
How many road accidents have alcohol as a factor?
What are the UK government’s advice for consumption of alcohol per week?
10ml pure ethanol
15mg/100ml
15mg/100ml an hour irrespective of amount consumed
- Disinhibition
- Loss motor coordination/impaired judgement
- Legal driving limit
- Increased loss coordination
- Amnesia
- Coma
- Death (vodka = 40 units)
50%
14 units for both men & women
What kind of effect does alcohol cause? 4
What are the physiological effects of alcohol? 5
What does alcohol stimulate?
What is the positive & negative reinforcement?
What are its dangers? 3
CNS depression, euphoria & enhanced self confidence due to depression of inhibitory control mechanisms in brain, impairment of intellect & sensory discrimination
Vasodilation, gastric secretion, urine production, liver damage & male impotence (erectile dysfunction)
Mesolimbic reward pathway - release of dopamine from neurones in VTA
Positive = pleasurable & euphoric effects
Negative = relief of stress
Dementia evidence with chronic abuse, foetal alcohol syndrome in pregnancy & potentiates effects of other drugs like BDZs (depressants x2)
How does alcohol induce liver damage? 3 steps
What are some of the receptors involved with ethanol? 7
Why is alcohol metabolism different to other drug metabolism?
Why does alcohol have fast on-set effects?
What is the 2 step metabolism of ethanol?
What is the linear rate of ethanol metabolism due to?
What is disulfiram/antabuse?
Main site of alcohol metabolism - fatty liver due to accumulation of fatty acids -> death of liver cells & formation fibrous scar tissue (fibrosis) -> cirrhosis (permanent damage)
- nAChRs
- ATP receptors (P2X)
- 5-HT3
- GABA-A
- NMDA
- glycine receptors
- voltage gated calcium channels
Rate of drug metabolism does not increase with blood concentration - zero order kinetics (linear & almost independent of concentration)
Very lipid soluble - readily absorbed by stomach & small intestine & crosses BBB quickly 5-10 mins & last hours
- Ethanol -> acetaldehyde by alcohol dehydrogenase & NAD+
- Acetaldehyde -> acetic acid by aldehyde dehydrogenase & NAD+
Limiting supply of NAD+ / nicotinamide adenine dinucleotide
Inhibitor of aldehyde dehydrogenase - makes people feel sick so effective at stopping people drinking alcohol
What is methanol metabolism?
How does it cause blindness?
What are the symptoms of hangover?
What is the economic cost of it?
What are the physical withdrawal symptoms?
What persists for longer?
Methanol -> Formaldehyde -> Formic acid by same enzymes
Formaldehyde acts on dehydrogenase enzymes in retina inducing retinal damage
Headache, diarrhoea, nausea, fatigue, sensitivity to light/sound, tremor, sweat, increased pulse
work absences & reduced performance
Tremor, sweating, nausea, confusion, hallucinations/delirium tremens
Cravings
How are Chlordiazepoxide and clomethiazole used to treat alcohol dependence/withdrawal?
Acamprosate?
Naltrexone?
Disulfiram?
Enhance GABA-A inhibitory receptors - but there is a risk of dependence
Modulates/normalises alcohol-disrupted brain activity in withdrawal
Opiate (inhibitory) receptor antagonist - reduces euphoria felt on inhibition by alcohol use reducing the positive reinforcing, rewarding effect
Used in aversion therapy (conditioning person to associate behaviour with undesirable stimulus) by inhibiting aldehyde dehydrogenase
