L10 - Alcohol Flashcards
What is cross tolerance?
Response to a novel drug is reduced because of tolerance developed in response to a related drug
Suggests that the two drugs affect a common nervous system target
Example: Barbiturates and benzodiazepines affect the inhibitory neurotransmitter GABA
3 types of tolerance?
Metabolic Tolerance
Number of enzymes needed to break down alcohol may
increase
Cellular Tolerance
Activities of brain cells may adjust to minimize the effect of alcohol
Learned Tolerance
People can learn to cope with effects of alcohol and therefore may not appear to be drunk
when do alcohol withdrawal symptoms usually start?
several hours after last dose, and intensify over several days before subsiding.
These are just symptoms that are a swingback furtherthan that normal… overcorrection
What is addiction caused by
Largely caused by the pleasurable effects of the drug
The ability of a drug to act as a positive reinforcer in animals sustains those behaviours and are also highly correlated with the abuse potential of the drug in humans
Short-acting substances have much greater potential for development of abuse or dependence (e.g. amphetamine, cocaine, some anxiolytics)
What kind of drugs have the most potential for abuse/dependence?
short-acting drugs
DSM-5 Alcohol use disorder
impairment or distress, as manifested by at least two of the following, occurring within a 12 month period:
1. Alcohol is often taken in larger amounts or over a longer period than was intended.
2. There is persistent desire or unsuccessful efforts to cut down or control, alcohol use
3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.
4. Craving, or a strong desire or urged to use alcohol.
5. Recurrent alcohol use, resulting in a failure to fulfil major role obligations
at work, school or home
6. Continued alcohol use despite persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol
7. Important social, occupational, or recreational activities are given up or reduced because of alcohol use.
8.Recurrent alcohol use in situations in which it is physically hazardous
9. Alcohol use is continued despite knowledge of having persistent or recurrent physical or psychological problems that is likely to have been caused or exacerbated by alcohol.
10.Tolerance, as defined by either of the following:
a) A need for markedly increased amounts of alcohol to achieve intoxication or desired effect.
b) A markedly diminished effect with continued use of the same amount of alcohol
11.Withdrawal, as manifested by either of the following:
a) Characteristic withdrawal syndrome for alcohol.
b) Alcohol (or a closely rented substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms
DSM-5 Smptoms of alcohol intoxication
One (or more) of the following signs or symptoms developing during, or shortly after, alcohol use:
Slurred speech
Incoordination
Unsteady gait
Nystagmus.
Impairment in attentional memory Stupor or coma
Mechanism of action for alcohol?
Stimulate GABA receptors (reduces tension)
Increases dopamine/serotonin levels (pleasurable
aspects of intoxication)
Inhibits glutamate receptors (cognitive actions)
is absorbed from stomach into the blood
What does peak BAC depend on
Peak blood alcohol concentration (BAC) depends on:
Amount and alcohol concentration of beverage
Rate of drinking
Food consumption and composition
Gastric emptying and gastric metabolism Hepatic first pass
What are the CNS effects of alcohol
Alcohol is a CNS depressant
But a transient stimulant at the lowest
doses
(1-2 drinks - stimulant, 6-7 drinks - depressant)
Apparent stimulatory effects result from depression of inhibitory control mechanisms in the brain
Characteristic response: euphoria, impaired thought processes, decreased mechanical efficiency
Which area of the brain does alcohol effect?
CEREBELLUM!!
anterior superior vermis.
anterior and superior cerebellum is affective, gives characteristic cerebellar signs of alcoholism, wide based high stepping gait.
What are some physical signs of alcohol abuse?
- facial puffiness
- dilated capillaries
- facial flush
- nail infection
- easy brusing
- sweating
- tremors
- rhinophyma (big nose?)
Some signs of alcohol withdrawal?
3-12 hours - tremors, shaking of body
3-12 hours - hallucinosis
12-48 hours - seizures
3-4 days - delirium tremens (confusion, agitation, sleep disorder).
what BAC is intoxication
0.08g/l
Concentration effect relo?
see slide
what is delirium tremens?
withdrawal delirium
generally between 48-72 hours
altered mental status, hallucinations, marked autonomic
instability
life-threatening
What are the earliest signs of ETOH withdrawal
anxiety, irritability, tremor, headache, insomnia, nausea,
tachycardia, hyperthermia, hyperactive reflexes
What is cross tolerant with alcohol
BENZOS - gaba agonist
What drugs are used to help with alcohol withdrawal?
Benzos - to reduce risk of seizures, and provide sedation and comfort.
Anticonvulsant - to reduce risk of seizures and kindling. helpful for protracted, longer, withdrawal
Thiamine supplementation - risk thiamine deficiency - wernicke/korsakoff.
What is wernicke’s encephalopathy
Severe deficiency of thiamine vitamin (B1)
Characterised by the classic triad of symptoms:
nystagmus, gaze palsies (96%) ataxia of gait (87%)
global confusional state (82%) but also
peripheral neuropathy (82%)
malnutrition (84%)
Neuropathology of WKS?
WKS produces lesions in:
the walls of the third ventricle and periaqueductal region the floor of the fourth ventricle
certain thalamic nuclei
the mamillary bodies
the terminal portion of the fornices
anterior superior vermis of the cerebellum
Lesions rarely seen in:
the cerebral cortex, corpus striatum, subthalamic and septal regions, cingulate gyri or hippocampi
avitaminosis?
A result of alcoholism - when food is replaced by drink.
decreased absorption of thiamine and decreased storage and use of thiamine by liver.
Different types or ARBI’s?
- wernicke’s encephalopathy (b1 deficiency)
- wernicke-s korsakoff syndrome (aka korsakoff psychosis)
What is wernicke’s encephalopathy?
arbi
b1 deficiency
Characterized by nystagmus, abducens and conjugate gaze palsies, ataxia, and mental disturbance (confusional state)
What is wernicke-korsakoff syndrome
(aka Korsakoff Psychosis or Korsakoff’s amnesia)
Retentive memory impaired out of proportion to other cognitive functions (chronic manifestation of Wernicke disease)
With treatment, recovery occurs in less than 20% of patients
What are thought to be the three predominant consequences of alcoholism on the brain?
- Premature aging/whole brain
- Right brain
- Frontal lobes
Which hemisphere of the brain is more vulnerable to alcoholism?
Right hemisphere is more vulnerable to the effects of alcoholism than the left hemisphere
Impairments in visuospatial functioning and
emotional processing
Emotional processing deficits also may be due to abnormalities in other brain regions (e.g., limbic system, frontal lobes)
What happens to the frontal lobes in alcoholism
Frontal lobes show increased susceptibility to alcoholism-related damage
Evidence from post-mortem neuropathological studies (Harper, 1998) and neuroimaging of living patients (Sullivan, 2000)
Also behavioural and neuropsychological deficits in executive functioning seem to be prominent in both currently-drinking and recently-detoxified alcoholics (e.g., Bechara et al., 2001)
What neurocognitive disorders are associated with ETOH
- alcohol (major nCD) non-amnestic-confabulatory type i.e. well-fed alcohol
- alcohol (major nCD) amnestic-confabulatory type i.e. wernicke-korsakoff
What are neurotoxic changes from ETOH from
cell loss
volume loss
synaptic plastic changes
association between alcohol use and dementia
Alcohol-induced brain injury ?
Localized loss of neurons and their axons, superior frontal cortex (= gray matter, GM)
Widespread shrinkage of neuronal cell bodies, in frontal, cingulate, and motor cortices
Reduced synaptic branching and dendritic pruning
Loss of white matter, demyelination (Harper, Kril et al. 1992-2001)
Enlarged ventricles and sulci
Brain tissue loss, especially frontal
Smaller size and other abnormalities of
subcortical structures, pons, hippocampus, and cerebellum
Dose-response relationship
Unclear if magnitude of injury similar in men
and women
Smaller tissue volumes in older alcoholics
reversibility of neuropsychological and radiological impairments?
- recovery is likely, some repor only partial
- cognition gets better with extended abstinence
this is through glial regeneration, synaptic plasticity.
What does the amnestic syndrome look like
an inability to learn new material
a normal STM
retrograde amnesia with a temporal gradient
improved by direct questioning
worse as move closer to the present in time
no time tags to events
preservation of skills and habits, and procedural memory
confabulation
decreased initiative and spontaneity, together with blunting of affect
areas of cog impairment for alcoholics?
Problem solving
Short term memory
- anterograte worse than retrograde, visual worse than verbal
Visuospatial ability
Balance and postural stability
Similar impairments for alcoholic men and women
medications for alcohol treatment?
disulfiram
naltrexone
acamprosate
disulfiram
a medication for alcohol treatment - aka antabuse
Inhibits aldehyde dehydrogenase and dopamine beta
hydroxylase
Aversive reaction when alcohol ingested- vasodilatation, flushing, N/V, hypotenstion/ hypertension, coma / death
Hepatotoxicity - check LFT’s and hep C
Neurologic with polyneuropathy / paraesthesias that slowly
increase over time and increased risk with higher doses
Psychiatric side effects - psychosis, depression, confusion, anxiety
Dermatologic rashes and itching
Watch out for disguised forms of alcohol - cologne, sauces, mouth wash, OTC cough meds, alcohol based hand sanitizers, etc
Naltrexone?
medication for alcohol treatment
Opioid antagonist thought to block mu receptors reducing
intoxication euphoria and cravings
Hepatotoxicity at high doses so check LFT’s
Acamprosate
aka campral
Unknown MOA but thought to stabilize neuron excitation and inhibition - may interact with GABA and Glutamate receptor - cleared renally (check kidney function)
What are treatment options for alcohol use disorder?
Medications support, education, skills training, psychiatric and psychological treatment, AA CBT - Contingency-Management therapy - relapse prevention - motivational interventions
What is Contingency-Management Therapy?
CBT for alcohol use disorder
Patient and family reinforce behaviours inconsistent with drinking
e.g., avoiding places associated with drinking
Teach problem drinker how to deal with uncomfortable situations
e.g., refusing the offer of a drink
