(9) alcohol Flashcards
What are alcohol’s costs to society and to the individual? Is alcohol use safe? (M2E Eeiim)
- most commonly used depressant
- 2nd most used drug
- ethanol use: widespread
- ethanol vs. isopropanol & methanol:
- ethanol: low doses, relatively safe
- isopropanol & methanol: unsafe at any dose
- isopropanol: v. potent
- methanol: toxic
How does it fare compared to other drugs? What does this mean for alcohol regulation? What does this mean for regulation of other drugs? (Smml L)
- socially accepted, but
- most harm caused to user & others
- most dangerous drug
- largest societal cumulative toll
- law: most illicit drug, most harmful but not true
How is alcohol measured in a drink?
- percentage alcohol: alcohol by volume (ABV)
- # of grams of alcohol per 100ml of solution
- proof of alcohol:
- 100 proof = double of ABV
What is the difference between fermentation and distillation?
- fermentation: yeast eats sugar in solution, alcohol as byproduct
- beers & nonfortified wines
- max 15% ABV
- distillation: cook alcohol out of fermented solution & leave stronger alcohol beverage
- liquors & fortified wines
- at least 20% ABV
What is the pharmacokinetics of alcohol? What implications arise from these pharmacokinetics (e.g. eating on an empty stomach)? (EOA Ha I BP)
- ethanol both water & lipid-soluble: many tissues absorb alcohol
- oral administration
- absorbed by gastrointestinal tract
- high ABV irritates, slows absorption:
- absorption better w/ mix, esp. carbonated: reduce irritation
- interferes w/ thiamine (vita. B1) transporter
- blood-alcohol concentration (BAC)
- peak absorption: ~45mins after
What is blood-alcohol concentration (BAC)?
grams of alcohol per 100ml blood
What is the biotransformation of alcohol (identify one notable metabolite)?
- metabolism occurs in stomach & liver: more alcohol metabolised in stomach, less drunk
- acetaldehyde: stuff of hangovers
- biotransformation process:
- alcohol uses alcohol dehydrogenase to turn into acetaldehyde
- acetaldehyde broken down into acetic acid & acetate by alcohol dehydrogenase
- acetate broken down into water & CO2
What is alcohol dehydrogenase polymorphism?
- make enzyme more efficient: make acetaldehyde from alcohol more quickly
- v. unpleasant effects: nauseated, v. sick, headache
- drink less, less risk of addiction
What are zero-order kinetics?
- elimination follows zero-order kinetics:
- removal of alcohol follows slow & steady pace independent of concentration in body (10-14mL/hour)
What are first-order kinetics?
- drank a lot, elimination rate switches to first-order kinetics:
- higher the concentration of alcohol in system, faster it will be eliminated
What are the pharmacodynamic actions of alcohol on GABAa receptors?
- positive allosteric modulator:
- binds to GABA receptor & enhances effects of GABA on receptor
- GABAa: chloride channels
- chronic administration: # of GABAa receptors decreases
- location of receptors dictate effects
What are alcohol’s effects on the cerebral cortex, hippocampus and thalamus? (Dais)
depressant effects on cognition:
- binds to GABA receptor on GABA neurons - indirectly activates beta-endorphins - silences thing that inhibits DA neurons, cause more DA release
What are alcohol’s effects on the NAcc and VTA?
changes motivation, effects related to addiction & greater DA release:
- binds to cells w/ GABA receptors, increase inhibition of cells, driving addiction process
What are the pharmacodynamic actions of alcohol on glutamate receptors?
- inhibits NMDA glutamate receptors:
- likely an antagonist
- blocks long-term memory processes
- NMDARs are special:
- long-term potentiation
- i.e. memory
- chronic administration: upregulate NMDARs
- effect of downregulated GABAa & upregulated NMDARs
What is long-term potentiation?
when there’s strong connection b/w pre & post-synaptic sides, NMDARs activated & calcium signals many changes
What are the pharmacodynamic actions of alcohol on L-type calcium channels?
- inhibits L-type calcium channels:
- results in widespread effects
- linked to decreased vasopressin, aka antidiuretic hormone (ADH): effects via hypothalamus
What does the vasopression/antidiuretic hormone (ADH) do?
released in relation to amount of water in body:
- more released: hold onto water
- block release: urinate more & become more dehydrated
What are alcohol’s effects via the hypothalamus?
- impaired cognition
- circadian disruption
- lowered blood pressure
- enhanced aggression:
- modest
- expectations of drinking or not more influential
What are the putative functions of alcohol with other receptors?
- increased beta-endorphin in VTA
- increased serotonin function in NAcc:
- via 5-HT3 & 5-HT2a receptors
- interaction w/ endocannabinoid system:
- relationship w/ memory & addiction (via DA system)
What are the pharmalogical effects of alcohol?
- low concentrations: stimulant-like effects
- higher concentrations: depressant effects
What are the neural mechanisms that explain the following effects of using alcohol? (disequilibrium, disinhibition, impulsivity)
- balance & equilibrium: alcohol affects cerebellum early on in drinking
- disinhibition: remove social inhibitions by drinking
- alcohol inhibits PFC
- related to poor judgement
- impulsivity
- alcohol priming: tendency for indiv. to have urge to drink more after 1 drink
- serious impediment to those benefits mentioned
What are the neural mechanisms that explain the following effects of using alcohol? (memory deficits, blackouts, aggression, dehydration)
- reaction time
- divided attention tasks
- memory deficits (episodic, semantic, but not working):
- blocking NMDAR & effects on hippocampus
- aggression: driven by L-type calcium channels & expectations
- mood, relaxation, stress: tension reduction hypothesis
- habitual users of alcohol using alcohol to relieve stress (instrumental use)
What is hormesis and its relation to alcohol?
toxic substance can be beneficial at low doses
- light chronic consumption (1-2 per day): decreased risk of ischemia, heart disorders, heart attack, stroke
- heavy chronic consumption (several per day): increased risk of ischemia, heart disorders, heart attack, stroke
What are the associated effects of BACs?
- stupor
- brownouts (fragmentary blackouts)
- blackouts (en bloc blackouts)
- “reversible drug-induced dementia”
- unconsciousness
- alcohol poisoning
What are the neural mechanisms that explain the following long-term risks of alcohol use? (Wernicke-Korsakoff’s syndrome, cancer, seizures, delerium tremen)
- cardiomyopathy: heart insufficiently working, not enough blood supply to body
- holiday heart syndrome: ppl drink more during holidays
- liver cirrhosis: accumulate damage in liver, no longer function properly
- fetal alcohol syndrome: pregnant woman pass alcohol to fetus
- cancer: first metabolite of alcohol - acetaldehyde
- Wernicke–Korsakoff’s syndrome: thiamine deficiency
- dementia, anterograde amnesis
What are the four types of tolerance?
- acute tolerance: during single drug-taking session, tolerance develops
- metabolic tolerance: adaption occurring at level of enzymes
- pharmacodynamic tolerance:
- over time, brain reduces # of GABA receptors & increases # of NMDARs on membrane
- leading to change in how alcohol affects cognition, synapses, NT systems
- behavioral tolerance: behavioural effects not as severe in long-term drinkers
- sensitisation: occurs for motivational effects of alcohol
What are the effects of withdrawal from alcohol?
- effects opposite to those in alcohol use
- risk of seizure: kindling
- alcohol withdrawal syndrome:
- Delirium tremens (DTs)
- tremors, shaking
What is kindling?
- each time withdraw from alcohol, make brain more spontaneously active
- more times do this, more likely to induce seizures when go cold turkey from alcohol
What is delirium tremens (DTs)?
- nightmares
- agitation
- confusion
- paranoia
- hallucinations
- hypertension
- sweating
- disoriented
What are the two profiles of potential alcohol addiction?
- alcohol addiction more common in men
- thought to be mediated by NAcc
- Type I
- older person (25+): at high risk b/c of psychosocial conditions
- Type 2
- before 25: family history of abusing alcohol, high genetic risk
What causes hangovers?
- common experience following alcohol consumption
- may be due to:
- acute withdrawal
- dehydration
- accumulations of acetaldehyde
- accumulations of acetate
- direct effects of alcohol
- other chemicals in alcoholic beverages: e.g. congeners
What are congeners?
substances that cause hangover type effects
How can one avoid a hangover?
- mostly, avoid getting drunk
- otherwise:
- drink water (before, during & after)
- fill stomach
- drink lighter-coloured alcoholic drinks: i.e. reduce congeners
- pain killers before bed:
- not tylenol (acetaminophen)
- not worth risks
What are treatments for alcohol addiction and why are they largely unsuccessful?
- Alcoholics Anonymous:
- 12-step program
- many members report social benefits
- CBT
- Pharmacotherapy:
- Disulfiram (Antabuse)
- Naltrexone
- Acamprosate
- most often unsuccessful
