Nicotine & Alcohol Flashcards
How many chemicals is contained in tobacco smoke?
~ 4000
How many people smoke tobacco worldwide?
~ 1 billion
What were the conclusions of a 50-year epidemiological study on cigarette smoking & mortality ?
Individuals who continue to smoke cigarettes die on average ~ 10 years younger than lifelong non-smokers
Cessation at age 50 halves risk of premature death
Cessation at age 30 almost removes increased risk
Describe the graph of plasma nicotine concentration (with inhalation)
Plasma nicotine conc rises quickly - inhaled nicotine absorbed into bloodstream via the lungs
Initial rapid fall of plasma nicotine conc - due to redistribution of nicotine between blood and other tissues
Slower decline of plasma nicotine conc - due to oxidative metabolism in the liver (to continine)
Where are Nicotinic ACh receptors (nAChRs) found at?
- The neuromuscular junction (NMJ)
- Autonomic ganglia - in the sympathetic & parasympathetic NS
- CNS
Nicotinic ACh receptors are…
Pentameric ligand-gated cation channels
It is estimated that …. Deaths per year in the UK are due to tobacco smoking
~ 100,000
Are the nicotinic ACh receptors at the skeletal neuromuscular junction (“muscle nAChRs”) pre- or post-synaptic ?
Postsynaptic
Are the nicotinic ACh receptors in the CNS & PNS (“neuronal nAChRs”) pre- or post-synaptic?
Presynaptic AND postsynaptic
Nicotine acting on nAChRs stimulates the release of several NTs including:
Dopamine
Noradrenaline
GABA (y-aminobutyric acid)
Endorphins
What does increased dopamine release cause ?
Psychoactive effects
What does increased noradrenaline release cause?
Increased attentiveness
What does increased GABA & endorphins cause?
Anxiolytic effects
What are the psychoactive effects of nicotine due to?
Nicotine activates nAChRs in the brain, causing the release of dopamine in the Mesolimbic dopamine pathway (or ‘reward centre’)
What is the mesolimbic dopamine pathway (mesolimbic reward pathway)?
Dopamine-releasing nerve cells in the VENTRAL TEGMENTAL AREA (at the top of the brainstem)
Relay messages about pleasure to nerve cells in the NUCLEUS ACCUMBENS
These nerve cells relay messages to the frontal region of the CEREBRAL CORTEX
What are the physiological effects of nicotine on the autonomic NS?
Mixture of sympathetic & parasympathetic effects:
Increased HR
Increased BP
Increased sweating
Decreased gastrointestinal motility
Release of adrenaline & noradrenaline from adrenal medulla
What are the physiological effects of nicotine on the CNS?
Stimulatory & inhibitory effects:
Symptoms of stimulation & arousal
Can alleviate stress & anxiety
May enhance learning & sensory performance
What is the physiological effect of nicotine on skeletal muscle?
Causes relaxation of skeletal muscle
- due to activation of nAChRs in the spinal cord, rather than direct effect at NMJ
What is the meaning of tolerance ?
Higher doses required to produce the same effect
What are the physical withdrawal symptoms (days-weeks) of smoking cessation?
Irritability
Restlessness
Attentional deficits
Sleep disturbances
Hunger
How do E-cigarettes work?
Contain an atomiser that is used to heat a solution of nicotine to create an aerosol or vapour that is inhaled
What are the advantages of nicotine replacement therapy for smoking cessation?
(Patches, gums, inhalers etc.)
E.g. Nicolette, Nicotinell & NiQuitin
Relieves withdrawal symptoms
Lower levels of nicotine than obtained from tobacco smoking
Avoids carcinogens present in tobacco smoke
How does Bupropion (smoking cessation therapy) work?
Has been used as an antidepressant, but its mode of action in smoking cessation is unclear
It may involve effects on dopamine & noradrenaline transmission
NICE concluded in 2002 that :
Nicotine replacement therapy & bupropion are amongst the most cost-effective health care treatments
How does Varenicline (smoking cessation therapy) work?
Partial agonist of alpha-4, beta-2 nAChRs
Causes a moderate & sustained increase in mesolimbic dopamine levels
Also, competitive binding with nicotine may reduce rewarding properties of nicotine during a relapse
Describe the efforts to develop a nicotine vaccine as a potential therapy to aid smoking cessation
Nicotine, conjugated to a carrier protein, acts as an antigen to stimulate antibody production
It is hoped that antibodies against nicotine would prevent it reaching the brain
What is the chemical formula for alcohol (ethanol) ?
CH3CH2OH
1 UK unit of alcohol =
10ml of pure ethanol
What is the equation to calculate units of alcohol?
Units of alcohol = ([volume, ml, consumed] x [% abv]) / 1000
% abv = percentage alcohol by volume
The % of alcohol by volume (abv) =
% abv = The number of units of alcohol in one litre of that drink
Advice for alcohol consumption was modified in January 2016 to:
14 units / week for men & women
Spread over 3 days or more
1 unit of alcohol raises blood alcohol levels by …
15mg / 100ml
Alcohol is metabolised at a rate of…
~15mg / 100ml per hour (~ 1 unit/hour)
(Rate of metabolism is irrespective of the amount consumed)
What is the effect of a blood alcohol concentration of < 30-50 (mg / 100ml)?
Disinhibition
What is the effect of a blood alcohol concentration of 50 (mg / 100ml) ?
Loss of motor coordination, judgement impaired
What is the effect of a blood alcohol concentration of 60 - 200 (mg / 100ml) ?
Increased loss of coordination
What is the effect of a blood alcohol concentration of 200 - 300 (mg / 100ml) ?
Amnesia
What is the effect of a blood alcohol concentration of 300 - 400 (mg / 100ml)?
Coma
What is the effect of a blood alcohol concentration of > 400 (mg / 100ml) ?
Death
What legal driving limit (UK) of blood alcohol concentration?
80 (mg / 100ml)
What are 5 physiological effects of alcohol?
Alcohol promotes:
Vasodilation
Gastric secretion
Urine production
Liver damage
Male impotence
What is the primary effect of alcohol consumption?
CNS depression
Alcohol use in pregnancy is associated with…
Foetal alcohol syndrome
Alcohol can potentiate the effects of other drugs - e.g….
Benzodiazepines
What causes positive and negative reinforcement of the mesolimbic dopamine pathway?
Alcohol stimulates mesolimbic dopamine pathway in the brain
Reinforcement can be ‘+’ and ‘-‘
+ reinforcement: due to pleasurable and euphoric effects
- reinforcement: e.g. due to the relief of stress
There is evidence for what neurodegenerative disease with chronic alcohol abuse ?
Dementia
Alcohol consumption impaires…
Intellectual performance & sensory discrimination
What are the 3 key stages of damage of the liver due to chronic alcohol use?
‘Fatty liver’ - accumulation of fatty acids
Can lead to death of liver cells and…
Fibrosis - formation of fibrous scar tissue
Can lead to…
Cirrhosis - permanent damage
Why can alcohol cause severe long-term effects on the liver?
The liver is the main site of alcohol consumption
What is unique about the rate of alcohol metabolism?
(In contrast to many drugs where the rate of drug metabolism increases with blood conc)…
The rate of metabolism of alcohol is linear and almost independent of concentration (‘zero-order kinetics’) and therefore blood alcohol conc doesn’t reach a plateau, but continues to accumulate
What are the 2 stages of ethanol oxidation in the liver ?
- Ethanol — alcohol dehydrogenase —> acetaldehyde
- Acetaldehyde — aldehyde dehydrogenase —> acetic acid
Ethanol is oxidised in the liver to acetic acid by which 2 enzymes?
Alcohol dehydrogenase
Aldehyde dehydrogenase
What cofactor do alcohol & aldehyde dehydrogenase require?
Nicotinamide adenine dinucleotide (NAD)
(NAD+ —> NADH)
What is the linear rate of ethanol metabolism due to ?
The limiting supply of NAD (nicotinic adenine dinucleotide)
- cofactor for the 2 enzymes: alcohol & aldehyde dehydrogenase which oxidise ethanol in the liver
Why is ethanol readily absorbed by the stomach & small intestine?
It’s highly lipid soluble
How is methanol metabolised ?
Methanol — alcohol dehydrogenase —> formaldehyde
Formaldehyde — aldehyde dehydrogenase —> Formic acid
What is Disulfiram and how does it work?
A medication used to treat chronic alcoholism by creating an unpleasant reaction when alcohol is consumed.
It inhibits aldehyde dehydrogenase (which breaks down acetaldehyde —> acetic acid) in the liver
This causes a build-up of acetaldehyde, a toxic substance that causes symptoms such as flushing, nausea and vomiting
What are the symptoms of an alcohol-induced hangover? (6)
Headache
Diarrhoea
Nausea
Fatigue
Sensitivity to light & sound
Tremor, sweating & increased pulse
What are the physical withdrawal symptoms of alcohol consumption (within hours, last few days)
Tremor
Sweating
Nausea
Confusion
Hallucination (delirium tremens)
