Week 3 Flashcards
What are the most important determinants of population alcohol consumption?
cost and availability
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
What are the psychological problems associated with acute intoxication with alcohol?
insomnia depression anxiety amnesia attempted suicide suicide
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
What is associated with alcohol dependence?
compulsion control tolerance withdrawal persistance neglect repertoire narrows reinstatement
What is the general rule of thumb for withdrawal effects?
opposite of intoxication symptoms and signs
What are typical withdrawal symptoms from alcohol?
excitable anxious hypervigilant high BP high pulse
What are thought to be the causes of alcohol problems?
price and availability
biological factors
behavioural models
socio-economic differences
What are psychiatric associations with cannabis?
dependence
psychosis
amotivational syndrome
cognitive impairment?
What are psychiatric associations with opiate dependence?
depression attempted suicide / suicide personality disorder PTSD no evidence for psychosis polydrug dependence likely
what are the psychiatric problems associated with stimulant drugs?
anxiety
depression
antisocial behaviours
paranoid psychosis
What transmitters / receptors does alcohol act on?
dopamine, opioids
increased GABA
How do stimulants work?
enhance transmission at the catecholaminergic / dopaminergic. serotonergic synapses
What are the effects of stimulants?
increased behavioural and motor activity increase alertness / sleep disruption euphoria confidence anxiety, insomnia and irritability
What is the stimulant toxidrome?
tachycardia hypertension risk of arrythmia sweaty hallucination agitation dilated pupils elevated temperature
What is the serotonin syndrome triad?
altered mental status
autonomic changes
neuromuscular effects
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
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
What are the acute neurological problems with stimulants?
tremor, myoclonus, rhabdomyolysis, movement disorders
seizures
neuropsychiatric - restlessness, irritability, violence, psychosis
autonomic - hyperpyrexia
What are the chronic neurological problems with stimulants?
anxiety sleep deprivation paranoia aggression paranoid psychosis cognitive dysfunction
How can stimulants cause vasospasm / sticky blood?
alpha adrenergic stimulation
platelet aggregation increased
accelerated atherosclerosis
Describe the opiate toxidrome?
pinpoint pupils respiratory depression bradycardia hypotension hypothermia pulmonary oedema seizures
What is the sedative toxidrome?
ataxia blurred vision coma confusion delirium sedation pupils likely to be normal
What are the acute neurological problems with sedatives?
coma
compressive nerve palsies
anoxic brain injury
What is the cholinergic toxidrome?
defecation urination miosis bronchoconstriction emesis lacrimation salivation
WHat effects does MDMA have?
stimulant toxidrome perceptual effects thermoregulatory problems hallucinations CV complications
What are the neurologic effects of hallucinogens?
rare reports of stroke
toxic psychosis
dangerous behaviour
Wernicke’s type syndrome - angel dust
What are the acute effects of organic solvents?
lightheadedness
hallucinations
What are the consequences of prolonged use of organic solvents?
cognitive impairment
diplopia / ataxia. nystagmus
coma
Describe the effects of cannabis
agonist at cannabanoid receptors - g protein linked receptors
alters mood
increases dopamine release
modulates opioid receptors
What are NPS?
new psychoactive substances
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
What is the main risk factor for alcoholic liver disease?
the amount type and frequency of alcohol consumption
What is the main pathway for alcohol metabolism for healthy people with safe alcohol consumption?
alchohol dehydrogenase enzyme which takes place in the cytosol
What are the overflow pathways for alcohol metabolism ?
MEOS - microsomal ethanol oxidising system (CYP2E1)
and catalase in the peroxisomes
What is one of the theories as to why some people are more susceptible to ALD than others?
genetic differences in ADH
What are the consequences of alcohol metabolism?
acetaldehyde production
acetate production
Increased NADH/NAD ratio
non-oxidative metabolism
What are the consequences of acetaldehyde production?
binds to proteins and DNA - immunogenic
Stimulates collagen production by stellate cells
What are the consequences of acetate production?
increased acetyl CoA promotes inflammation by histone acetylation
What is the consequence of an increased NADH/NAD ratio?
increased fatty acid synthesis, reduced fatty acid oxidation, promotes steatosis
What is the consequence of non-oxidative metabolism?
fatty acid ether ester production which promotes steatosis
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
Describe TNF alpha action in regards to ALD
promotes apoptosis and necrosis, and activates stellate cells to produce collagen leading to fibrosis
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
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
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
Describe apoptosis
natural cell death
stimulated by cell signals
beneficial
produces cell fragments that are able to send signals that facilitate phagocytosis
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
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)
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)
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
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
WHat is the main zones of the liver effected by fatty liver disease?
2 and 3
How is a fibrotic liver assessed?
a fibroscan
replacing biopsies
What are the signs of chronic liver disease?
stigmata - spiders foetor encephalopathy prolonged PT hypoalbuminaemia
What are the signs of portal hypertension?
caput medusa
hypersplenism
thrombocytopenia
WHat are the results of raised portal pressure?
hypersplenism oesophageal varices encephalopathy hyperdynamic circulation ascites hepato-renal syndrome
What is the other name for Korsakoff syndrome?
amnestic syndrome
What do 50% of alcoholic adults show problems in?
spatial skills
planning
learning and memory
What are the different types of alcohol related brain damage?
neuropathies
cerebellar degeneration
dementia
wernicke-korsakoff syndrome
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
What are the predisposing factors for nutritional or thiamine deficiency ?
weight loss in past year
reduced BMI
high carb intake
recurrent episodes of vomiting
What are the symptoms of wernicke-korsakoff syndrome?
confusion eye symptoms gaze paralyis nystagmus gait ataxia
What areas are affected in korsakoffs disease?
maxillary bodies and mediodorsal thalamic nucleus
Describe korsakoffs disease
an amnesic syndrome with impaired recent memory and relatively intact intellectual function
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
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
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
