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1

What are the most important determinants of population alcohol consumption?

cost and availability

2

How is the relationship between alcohol and mental health problems complex?

the symptoms may be a direct consequence of substance misuse
the mental disorder may predate the substance abuse
the 2 disorders may exist coincidentally in the same individual

3

What are the psychological problems associated with acute intoxication with alcohol?

insomnia
depression
anxiety
amnesia
attempted suicide
suicide

4

What are the psychological problems associated with regular heavy drinking?

insomnia
depression
anxiety
attempted suicide / suicide
changes in personality
amnesia
delirium tremens
alchohol hallucinosis
dementia
association with other addictions

5

What is associated with alcohol dependence?

compulsion
control
tolerance
withdrawal
persistance
neglect
repertoire narrows
reinstatement

6

What is the general rule of thumb for withdrawal effects?

opposite of intoxication symptoms and signs

7

What are typical withdrawal symptoms from alcohol?

excitable
anxious
hypervigilant
high BP
high pulse

8

What are thought to be the causes of alcohol problems?

price and availability
biological factors
behavioural models
socio-economic differences

9

What are psychiatric associations with cannabis?

dependence
psychosis
amotivational syndrome
cognitive impairment?

10

What are psychiatric associations with opiate dependence?

depression
attempted suicide / suicide
personality disorder
PTSD
no evidence for psychosis
polydrug dependence likely

11

what are the psychiatric problems associated with stimulant drugs?

anxiety
depression
antisocial behaviours
paranoid psychosis

12

What transmitters / receptors does alcohol act on?

dopamine, opioids
increased GABA

13

How do stimulants work?

enhance transmission at the catecholaminergic / dopaminergic. serotonergic synapses

14

What are the effects of stimulants?

increased behavioural and motor activity
increase alertness / sleep disruption
euphoria
confidence
anxiety, insomnia and irritability

15

What is the stimulant toxidrome?

tachycardia
hypertension
risk of arrythmia
sweaty
hallucination
agitation
dilated pupils
elevated temperature

16

What is the serotonin syndrome triad?

altered mental status
autonomic changes
neuromuscular effects

17

How does cocaine act?

quick onset
peak levels in 30 minutes
rapid BBB penetration
short half life
Blocks Da, NE and 5HT reup-take
pleasure effect and readiness

18

How do amphetamines work?

quick onset
peak levels in 30 minutes
BBB penetration
long half life
enhance release of DA and NE from pre-synaptic terminals

19

What are the acute neurological problems with stimulants?

tremor, myoclonus, rhabdomyolysis, movement disorders
seizures
neuropsychiatric - restlessness, irritability, violence, psychosis
autonomic - hyperpyrexia

20

What are the chronic neurological problems with stimulants?

anxiety
sleep deprivation
paranoia
aggression
paranoid psychosis
cognitive dysfunction

21

How can stimulants cause vasospasm / sticky blood?

alpha adrenergic stimulation
platelet aggregation increased
accelerated atherosclerosis

22

Describe the opiate toxidrome?

pinpoint pupils
respiratory depression
bradycardia
hypotension
hypothermia
pulmonary oedema
seizures

23

What is the sedative toxidrome?

ataxia
blurred vision
coma
confusion
delirium
sedation
pupils likely to be normal

24

What are the acute neurological problems with sedatives?

coma
compressive nerve palsies
anoxic brain injury

25

What is the cholinergic toxidrome?

defecation
urination
miosis
bronchoconstriction
emesis
lacrimation
salivation

26

WHat effects does MDMA have?

stimulant toxidrome
perceptual effects
thermoregulatory problems
hallucinations
CV complications

27

What are the neurologic effects of hallucinogens?

rare reports of stroke
toxic psychosis
dangerous behaviour
Wernicke's type syndrome - angel dust

28

What are the acute effects of organic solvents?

lightheadedness
hallucinations

29

What are the consequences of prolonged use of organic solvents?

cognitive impairment
diplopia / ataxia. nystagmus
coma

30

Describe the effects of cannabis

agonist at cannabanoid receptors - g protein linked receptors
alters mood
increases dopamine release
modulates opioid receptors

31

What are NPS?

new psychoactive substances

32

Describe legal highs

contain substances which produce similar psychoactive effects to traditional illegal drugs. There is no officially agreed list of substances that are categorised as legal highs

33

What is the main risk factor for alcoholic liver disease?

the amount type and frequency of alcohol consumption

34

What is the main pathway for alcohol metabolism for healthy people with safe alcohol consumption?

alchohol dehydrogenase enzyme which takes place in the cytosol

35

What are the overflow pathways for alcohol metabolism ?

MEOS - microsomal ethanol oxidising system (CYP2E1)
and catalase in the peroxisomes

36

What is one of the theories as to why some people are more susceptible to ALD than others?

genetic differences in ADH

37

What are the consequences of alcohol metabolism?

acetaldehyde production
acetate production
Increased NADH/NAD ratio
non-oxidative metabolism

38

What are the consequences of acetaldehyde production?

binds to proteins and DNA - immunogenic
Stimulates collagen production by stellate cells

39

What are the consequences of acetate production?

increased acetyl CoA promotes inflammation by histone acetylation

40

What is the consequence of an increased NADH/NAD ratio?

increased fatty acid synthesis, reduced fatty acid oxidation, promotes steatosis

41

What is the consequence of non-oxidative metabolism?

fatty acid ether ester production which promotes steatosis

42

Describe ROS production

largely through MEOS but catalase may also contribute
production of hydrogen peroxide and superoxide ions
activates redox sensitive transcription factors such as NF-KB which leads to increased TNF alpha production
Promotes lipid per oxidation which promotes inflammation and damages mitochondrial membranes leading to apoptosis

43

Describe TNF alpha action in regards to ALD

promotes apoptosis and necrosis, and activates stellate cells to produce collagen leading to fibrosis

44

What effect does alcohol have on intestinal permeability?

increases it
leads to portal circulation endotoxaemia
this promotes activation of Kupffer cells which in turn promote liver injury and TNF alpha release

45

Describe the intrinsic apoptosis pathway

initiated by oxidative stress
leads to leakage of pro-apoptotic factors from the mitochondria (cytochrome C) regulated by Bcl2 proteins
Pro-apoptotic factors from mitochondria activate cascades leading to cell degredation

46

Describe the extrinsic apoptotic pathway

initiated by TNF - alpha
binding to TNF receptors leads to Caspase activation via FADD (Fas-associated death domain) and TRADD (TNF receptor associated death domain) proteins

47

Describe apoptosis

natural cell death
stimulated by cell signals
beneficial
produces cell fragments that are able to send signals that facilitate phagocytosis

48

Describe necrosis

traumatic cell death
stimulated by factors external to the cells
fatal
cannot send signals, leads to build up of dead tissue and cell debris

49

Describe mitochondrial susceptibility in ALD

mitochondria in patients with chronic alcohol excess are more susceptible to ROS
normally protected by mitochondrial survival factors (MnSOD, Blf1 BclXL) and anti-oxidants (glutathione)

50

How can malnutrition make ALD more likely?

depletion of trace elements (zinc) may exacerbate ROS production and promote apoptosis
vitamine deficiency may lead to impaired metabolism of methionine and reduction into glutathione (normally protective against oxidative stress)

51

Describe how obesity increases the risk of ALD

alcohol induces a lipodystrophy - reduction in peripheral fat and increase in visceral fat
induction of CTP2E1 by increased free FA, insulin resistance and alcohol
increased ROS and further insulin resistance
Metabolism of FFas to w hydroxylated farry acids
obesity induced pro-inflammatory state

52

WHat is the main test that determines whether NAFLD orALD is more likely?

AST:ALT ratio is usually very elevated in ALD due to mitochondrial damage which raises ALT

53

WHat is the main zones of the liver effected by fatty liver disease?

2 and 3

54

How is a fibrotic liver assessed?

a fibroscan
replacing biopsies

55

What are the signs of chronic liver disease?

stigmata - spiders
foetor
encephalopathy
prolonged PT
hypoalbuminaemia

56

What are the signs of portal hypertension?

caput medusa
hypersplenism
thrombocytopenia

57

WHat are the results of raised portal pressure?

hypersplenism
oesophageal varices
encephalopathy
hyperdynamic circulation
ascites
hepato-renal syndrome

58

What is the other name for Korsakoff syndrome?

amnestic syndrome

59

What do 50% of alcoholic adults show problems in?

spatial skills
planning
learning and memory

60

What are the different types of alcohol related brain damage?

neuropathies
cerebellar degeneration
dementia
wernicke-korsakoff syndrome

61

What are the predisposing factors for neurotoxicity?

genetic
quantity / frequency of alcohol use
severity of dependence
frequent episodes of acute intoxication
withdrawal syndromes
other drugs use
concurrent liver damage

62

What are the predisposing factors for nutritional or thiamine deficiency ?

weight loss in past year
reduced BMI
high carb intake
recurrent episodes of vomiting

63

What are the symptoms of wernicke-korsakoff syndrome?

confusion
eye symptoms
gaze paralyis
nystagmus
gait ataxia

64

What areas are affected in korsakoffs disease?

maxillary bodies and mediodorsal thalamic nucleus

65

Describe korsakoffs disease

an amnesic syndrome with impaired recent memory and relatively intact intellectual function

66

Describe the complexity of cognitive impairment with alcohol misuse which includes other factors

intoxication
seizures
alcohol neurotoxicity
vitamin deficiecny
hypoglycaemia
head injury
cerebellar accidents
withdrawal deltrium
hepatic encephalopathy
hypoxia
non-alcholic related cerebral pathology in older people

67

Describe alcohol and the physiology of aging

decreased lean body mass and total body water = increased blood alcohol conc
Age-related disease in gastric alcohol dehydrogenase increases BAC
liver oxidation decreases with age, increases BAC
sensitivity of brain to alcohol increases with age

68

Describe foetal alcohol syndrome

a serious developmental disorder caused by prenatal alcohol exposure of the foetus and is characterised by =
prenatal/post natal growth retardation
central NS dysfunction
characteristic craniofacial abnormalities