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PHAR0002 > Nicotine & Alcohol > Flashcards

Nicotine & Alcohol Flashcards

1
Q

How many chemicals is contained in tobacco smoke?

A

~ 4000

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2
Q

How many people smoke tobacco worldwide?

A

~ 1 billion

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3
Q

What were the conclusions of a 50-year epidemiological study on cigarette smoking & mortality ?

A

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

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4
Q

Describe the graph of plasma nicotine concentration (with inhalation)

A

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)

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5
Q

Where are Nicotinic ACh receptors (nAChRs) found at?

A
  1. The neuromuscular junction (NMJ)
  2. Autonomic ganglia - in the sympathetic & parasympathetic NS
  3. CNS
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6
Q

Nicotinic ACh receptors are…

A

Pentameric ligand-gated cation channels

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7
Q

It is estimated that …. Deaths per year in the UK are due to tobacco smoking

A

~ 100,000

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8
Q

Are the nicotinic ACh receptors at the skeletal neuromuscular junction (“muscle nAChRs”) pre- or post-synaptic ?

A

Postsynaptic

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9
Q

Are the nicotinic ACh receptors in the CNS & PNS (“neuronal nAChRs”) pre- or post-synaptic?

A

Presynaptic AND postsynaptic

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10
Q

Nicotine acting on nAChRs stimulates the release of several NTs including:

A

Dopamine
Noradrenaline
GABA (y-aminobutyric acid)
Endorphins

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11
Q

What does increased dopamine release cause ?

A

Psychoactive effects

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12
Q

What does increased noradrenaline release cause?

A

Increased attentiveness

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13
Q

What does increased GABA & endorphins cause?

A

Anxiolytic effects

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14
Q

What are the psychoactive effects of nicotine due to?

A

Nicotine activates nAChRs in the brain, causing the release of dopamine in the Mesolimbic dopamine pathway (or ‘reward centre’)

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15
Q

What is the mesolimbic dopamine pathway (mesolimbic reward pathway)?

A

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

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16
Q

What are the physiological effects of nicotine on the autonomic NS?

A

Mixture of sympathetic & parasympathetic effects:
Increased HR
Increased BP
Increased sweating
Decreased gastrointestinal motility

Release of adrenaline & noradrenaline from adrenal medulla

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17
Q

What are the physiological effects of nicotine on the CNS?

A

Stimulatory & inhibitory effects:

Symptoms of stimulation & arousal
Can alleviate stress & anxiety
May enhance learning & sensory performance

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18
Q

What is the physiological effect of nicotine on skeletal muscle?

A

Causes relaxation of skeletal muscle
- due to activation of nAChRs in the spinal cord, rather than direct effect at NMJ

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19
Q

What is the meaning of tolerance ?

A

Higher doses required to produce the same effect

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20
Q

What are the physical withdrawal symptoms (days-weeks) of smoking cessation?

A

Irritability
Restlessness
Attentional deficits
Sleep disturbances
Hunger

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21
Q

How do E-cigarettes work?

A

Contain an atomiser that is used to heat a solution of nicotine to create an aerosol or vapour that is inhaled

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22
Q

What are the advantages of nicotine replacement therapy for smoking cessation?

(Patches, gums, inhalers etc.)
E.g. Nicolette, Nicotinell & NiQuitin

A

Relieves withdrawal symptoms
Lower levels of nicotine than obtained from tobacco smoking
Avoids carcinogens present in tobacco smoke

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23
Q

How does Bupropion (smoking cessation therapy) work?

A

Has been used as an antidepressant, but its mode of action in smoking cessation is unclear

It may involve effects on dopamine & noradrenaline transmission

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24
Q

NICE concluded in 2002 that :

A

Nicotine replacement therapy & bupropion are amongst the most cost-effective health care treatments

25
Q

How does Varenicline (smoking cessation therapy) work?

A

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

26
Q

Describe the efforts to develop a nicotine vaccine as a potential therapy to aid smoking cessation

A

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

27
Q

What is the chemical formula for alcohol (ethanol) ?

A

CH3CH2OH

28
Q

1 UK unit of alcohol =

A

10ml of pure ethanol

29
Q

What is the equation to calculate units of alcohol?

A

Units of alcohol = ([volume, ml, consumed] x [% abv]) / 1000

% abv = percentage alcohol by volume

30
Q

The % of alcohol by volume (abv) =

A

% abv = The number of units of alcohol in one litre of that drink

31
Q

Advice for alcohol consumption was modified in January 2016 to:

A

14 units / week for men & women
Spread over 3 days or more

32
Q

1 unit of alcohol raises blood alcohol levels by …

A

15mg / 100ml

33
Q

Alcohol is metabolised at a rate of…

A

~15mg / 100ml per hour (~ 1 unit/hour)

(Rate of metabolism is irrespective of the amount consumed)

34
Q

What is the effect of a blood alcohol concentration of < 30-50 (mg / 100ml)?

A

Disinhibition

35
Q

What is the effect of a blood alcohol concentration of 50 (mg / 100ml) ?

A

Loss of motor coordination, judgement impaired

36
Q

What is the effect of a blood alcohol concentration of 60 - 200 (mg / 100ml) ?

A

Increased loss of coordination

37
Q

What is the effect of a blood alcohol concentration of 200 - 300 (mg / 100ml) ?

A

Amnesia

38
Q

What is the effect of a blood alcohol concentration of 300 - 400 (mg / 100ml)?

A

Coma

39
Q

What is the effect of a blood alcohol concentration of > 400 (mg / 100ml) ?

A

Death

40
Q

What legal driving limit (UK) of blood alcohol concentration?

A

80 (mg / 100ml)

41
Q

What are 5 physiological effects of alcohol?

A

Alcohol promotes:

Vasodilation
Gastric secretion
Urine production
Liver damage
Male impotence

42
Q

What is the primary effect of alcohol consumption?

A

CNS depression

43
Q

Alcohol use in pregnancy is associated with…

A

Foetal alcohol syndrome

44
Q

Alcohol can potentiate the effects of other drugs - e.g….

A

Benzodiazepines

45
Q

What causes positive and negative reinforcement of the mesolimbic dopamine pathway?

A

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

46
Q

There is evidence for what neurodegenerative disease with chronic alcohol abuse ?

A

Dementia

47
Q

Alcohol consumption impaires…

A

Intellectual performance & sensory discrimination

48
Q

What are the 3 key stages of damage of the liver due to chronic alcohol use?

A

‘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

49
Q

Why can alcohol cause severe long-term effects on the liver?

A

The liver is the main site of alcohol consumption

50
Q

What is unique about the rate of alcohol metabolism?

A

(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

51
Q

What are the 2 stages of ethanol oxidation in the liver ?

A
  1. Ethanol — alcohol dehydrogenase —> acetaldehyde
  2. Acetaldehyde — aldehyde dehydrogenase —> acetic acid
52
Q

Ethanol is oxidised in the liver to acetic acid by which 2 enzymes?

A

Alcohol dehydrogenase
Aldehyde dehydrogenase

53
Q

What cofactor do alcohol & aldehyde dehydrogenase require?

A

Nicotinamide adenine dinucleotide (NAD)

(NAD+ —> NADH)

54
Q

What is the linear rate of ethanol metabolism due to ?

A

The limiting supply of NAD (nicotinic adenine dinucleotide)

  • cofactor for the 2 enzymes: alcohol & aldehyde dehydrogenase which oxidise ethanol in the liver
55
Q

Why is ethanol readily absorbed by the stomach & small intestine?

A

It’s highly lipid soluble

56
Q

How is methanol metabolised ?

A

Methanol — alcohol dehydrogenase —> formaldehyde

Formaldehyde — aldehyde dehydrogenase —> Formic acid

57
Q

What is Disulfiram and how does it work?

A

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

58
Q

What are the symptoms of an alcohol-induced hangover? (6)

A

Headache
Diarrhoea
Nausea
Fatigue
Sensitivity to light & sound
Tremor, sweating & increased pulse

59
Q

What are the physical withdrawal symptoms of alcohol consumption (within hours, last few days)

A

Tremor
Sweating
Nausea
Confusion
Hallucination (delirium tremens)

PHAR0002 (20 decks)

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