Drugs of abuse 3 -Alcohol Flashcards

1
Q

Where was alcohol first believed to be used

A

China – 9000 B.C.

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2
Q

What is the first known distilling technique for alcohol

A

Mongolian Still’ – 700 A.D

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3
Q

Summarise the epidemiology of alcohol consumption

A

 Epidemiology – high alcohol consumption especially in Europe, Greenland and Russia.

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4
Q

How can we calculate the absolute amount of alcohol

A

% ABV x 0.78 = g alcohol/100ml (ABV = alcohol by volume)

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5
Q

How can we calculate the number of units in a given volume of alcohol

A

ABV% x volume (ml)/1000

1 unit = 10ml or 8g of absolute alcohol

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6
Q

What is the recommended weekly allowance of alcohol for men and women

A

Men & Women;  14 units/week LOW RISK

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7
Q

Define binge drinking

A

Binge drinking i.e. > 8 units in one sitting; 18% (> 30%) ↓
(16-24 yrs)

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8
Q

What is 0.01% of alcohol in the blood equal to

A

BLOOD LEVELS – 0.01% = 10mg/100ml blood

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9
Q

Describe the link between alcohol consumption and drink driving

A

Levels of alcohol in blood (for the same number of drinks) depends on your gender and body weight.
Legal driving limit is below 80 mg/100 ml- i.e 0.08% alcohol.
Subtract 0.01% for wach 40 minutes of drinking.
1 drink = 1.50z 80 proof spirit
12Oz 5% beer
5Oz 12% wine

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10
Q

Where is alcohol absorbed

A

20% - stomach

80% - small intestine

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11
Q

What is the speed of alcohol intoxication proportional to and why

A

 Speed of onset of intoxication >proportional> to gastric emptying.
o Post-prandial, the stomach does not empty often as it needs to break down food thus alcohol is not absorbed very well – i.e. eating a meal decreases speed of onset.

On an empty stomach- fluid will just hit stomach lining and will leave the stomach stragiht away.

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12
Q

What percentage of the alcohol absorbed is metabolised

A

Metabolism – only 90% is metabolised, 10% breathed off

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13
Q

Where is alcohol metabolised

A

 85% of metabolism occurs in the liver, 15% occurs in the GIT.

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14
Q

Describe the metabolism of alcohol in the liver

A

o Alcohol  acetaldehyde (toxic) via:
 75% - Alcohol dehydrogenase.
 25% - Mixed function oxidase.
• MFO is most significantly upregulated in chronic alcoholics (only 25% in naïve drinkers).- this is the reason for alcohol tolerance.

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15
Q

Describe the metabolism of alcohol in the gut

A

The stomach contains alcohol dehydrogenase, which is responsible for 15% of alcohol metabolism
Women have 50% less alcohol dehydrogenase in their stomachs than men

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16
Q

Why would one large dose of alcohol give a larger plasma concentration than several smaller doses

A

The liver enzymes that are responsible for metabolising alcohol are saturable
o One high-dose alcohol bolus will saturate the enzymatic system and lead to a higher intoxication as opposed to the same absolute amount of alcohol over say 4 separate doses.

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17
Q

Describe the typical composition of a female

A
Body water: 50%
e.g. 60kg woman
65% ICF; ~ 20L 
35% ECF; ~ 10L
	(incl 2L plasma)
18
Q

Describe the typical composition of a male

A
Body water: 59%
e.g. 75kg man
65% ICF; ~ 30L 
35% ECF; ~ 15L
	(incl 3L plasma)
19
Q

A man and a woman of similar height and weight share a bottle of wine. Explain why the blood alcohol levels in the woman are likely to be higher.

A

 Men have a greater volume of body water (and women have more adipose tissue) which allows alcohol to be more widely distributed in men so at a lower concentration. Alcohol is water soluble adn so will distribute more in the blood.
 Men have more ADH as well so more ability to metabolise.

20
Q

Describe the metabolism of acetaldehyde in the gut and liver

A

 Liver and GIT metabolism:
o Acetaldehyde  Acetic acid via:
 Aldehyde dehydrogenase.
• Polymorphisms can be found in this enzyme leading to Asian flush.

21
Q

What drug can be used as an alcohol aversion therapy

A

Disulfiram – it is an aldehyde dehydrogenase inhibitor so it promotes the build up of acetaldehyde, which is responsible for most of the negative feelings associated with drinking

22
Q

Why do asians tend to tolerate alcohol poorly

A

There is a common genetic polymorphism in the aldehyde dehydrogenase gene meaning that some people (particularly Asians) can’t convert acetaldehyde to acetic acid as efficiently so acetaldehyde builds up and makes them feel bad

23
Q

Why does alcohol have a low pharmacological potency

A

 Alcohol has a LOW potency (it is a very general molecule).
o Influences a lot of receptors due to its uncomplicated shape however doesn’t fit a lot of the receptors very well so not a lot of efficacy.

24
Q

Compare the potency of alcohol to nicotine and cocaine

A

Amounts to produce an effect:
Nicotine 20ng/ml

Cocaine 200ng/ml

Alcohol 200g/ml

25
Q

What is the primary effect of alcohol

A

Depressant

26
Q

Describe how low dose alcohol may cause CNS agitation

A

Depends on degree of CNS excitability:
This in turn depends on your personality and environment (i.e whether you are in a social or un-social setting)
Low dose alcohol is morel likely to cause CNS agitation in low dose settings, and thus give feelings of increased confidence etd
However, the depressant effects will soon kick in as the dose is increased.

Initial stimulatory effects result from depression of inhibitory control pathways

27
Q

Describe the 3 major CNS targets of alcohol

A

NMDA – alcohol decreases NMDA receptor function (allosteric modulation) - NMDA is excitatory for the brain

Ca2+ channels – alcohol reduces Ca2+ channel function meaning that there is less calcium influx, which negatively affects neurotransmitter exocytosis

GABA:
Post-synpatically- alcohol can bind to GABA receptor- leading to chloride ion influx and thus hyperpolarisation
Pre-synpatically- increase release of allopregenolone- which is a neural steroid and has efficacy for the GABA receptor.

28
Q

What may be the consequences of the action of alcohol on each of the CNS targets

A

Enhancement of GABA-mediated inhibition (?? Sedative/anxiolytic effects)
Inhibition of calcium entry through voltage gated calcium channels
Inhibition of NMDA receptor function (?? Loss of memory)

29
Q

What is important to remember about the acute CNS effects of alcohol

A

Important – CNS is functionally more complex than any other system in the body relationship between behaviour of individual cells and that of the organ as a whole is often unclear
This is worsened by alcohol’s low potency and selectivity.

30
Q

Describe how alcohol may cause euphoria

A

§ Alcohol binds to the m-receptor to inhibit GABA release.
§ Less inhibitory GABA means less inhibition on DA release by the VTA DA neurones into the NAcc.

Opiates may also bind to this receptor

31
Q

Describe how alcohol can impair both sensory and motor function

A

Sensory function i.e. Mood Changes e.g. self confidence, euphoria (highly labile at higher concentrations) Memory Loss Powers of discrimination and concentration
Motor function i.e. Slurred speech Prolonged reaction time Loss of coordination

32
Q

Describe the effects of alcohol on the different parts of the CNS

A

Depresses all of these functions:
Corpus Collosum - Passes info from the left brain (rules, logic)
to the right brain (impulse, feelings) and vice versa.

Hypothalamus - Controls appetite, emotions, temperature,
and pain sensation.

Reticular Activating System –
Consciousness

Hippocampus - Memory

Cerebellum - Movement
and coordination

Basal Ganglia –
Perception of time

33
Q

Describe how alcohol can cause cutaneous vasodilation (flushing)

A

Alcohol causes vasodilation (this is thought to be due to acetaldehyde) - acts on pre-capillary sphincters of cutaneous vessels.
It causes decrease calcium influx and increased prostaglandins à vasodilation

34
Q

Describe how alcohol may cause tachycardia and hypertension

A

Alcohol decreases the sensitivity of baroreceptors
This means decreased baroreceptor firing à decreased parasympathetic firing + decreased inhibition of sympathetic firing à INCREASED HEART RATE

35
Q

Describe normal baroreceptor control of BP

A

Increased firing rate – stimulates PSNS neurone- which projects to the heart to decrease HR. Also stimulates inhibitory interneurone which is linked to the SNS neurone- therefore we have less vasoconstriction and decreased HR.

36
Q

Describe how alcohol may cause diuresis

A

Alcohol inhibits vasopressin release from the neurohypophysis
This means that alcohol is a powerful diuretic

This may be due to acetaldehyde
Remember -vasopressin helps you to retain water.

37
Q

What is the role of thiamine in the body

A

The thiamine requirement for healthy individuals is related to their carbohydrate intake and is between 1–2mg per day: this requirement increases with alcohol misuse. The body can only store between 30–50 mg of thiamine, thus body stores of individuals on a thiamine deficient diet are likely to be depleted in four-to-six weeks. Further thiamine deprivation causes a significant decrease in the activity of many enzymes which play a key role in metabolism. Thiamine acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt.

38
Q

Describe the effects of chronic alcoholism on the CNS

A

Most of calories come from alcohol- can lead to thiamine deficiency
Thiamine is an important cofactor for the enzymes involved in energy metabolism and thus is important for cerebral energy utilisation.

A deficiency in thiamine can therefore lead to:
Brain regions with high metabolic demand – impaired metabolism, NMDA excitotoxicity, ROS.

39
Q

Describe the effects of impaired metabolism, NMDA excitotoxicity and ROS on different regions of the CNS

A

Chronic alcohol caused cortical atrophy and a loss of cerebral white matter à dementia
Confusion (encephalopathy)
oculomotor symptoms
Ataxia – Cerebellar cortex degeneration - gait

40
Q

Summarise Wernicke-Korsakoff syndrome

A

Wernicke’s encephalopathy (WE) is an acute neuropsychiatric condition due to an initially reversible biochemical brain lesion caused by overwhelming metabolic demands on brain cells that have depleted intracellular thiamine (vitamin B1). This imbalance leads to a cellular energy deficit, focal acidosis, regional increase in glutamate, and ultimately cell death. Classically, Wernicke’s encephalopathy is characterised by the triad ophthalmoplegia (paralysis of muscles surrounding the eye), ataxia, and confusion. However, only 10% of patients exhibit all three features, and other symptoms may also be present. The primary neurological-related injury caused by thiamine deficiency in WE is three-fold: oxidative damage, mitochondrial injury leading to apoptosis, and directly stimulating a pro-apoptotic pathway.

41
Q

Describe and explain how chronic alcoholism can cause Wernicke-Korsakoff syndrome

A

Wernicke-Korsakoff syndrome is caused by thiamine (vitamin B1) deficiency
Chronic alcoholics tend to have a bad diet
Thiamine is an important cofactor in the generation of ATP within cells
The lack of thiamine impairs the Krebs’ cycle and leads to the build up of oxidative stress within the cells
The oxidative stress can cause mitochondrial damage and apoptosis
Wenicke’s Encephalopathy – caused by mitochondrial injury (thalamus/hypothalamus)- affects the 3rd ventricle and aqueduct.- reversible
Korsakoff’s Psychosis – cell apoptosis in the brain – this is irreversible and the patient will probably die - deep brain structures hippocampus

42
Q

Describe a typical presentation of Korsakoff’s Psychosis

A

Korsakoffs psychosis is associated with polyneuritis, and is characterized by an impaired ability to acquire new information and by a substantial, but irregular memory loss for which the patient often attempts to compensate through confabulation. Irreversible – neuronal cell death.