W 8 - Alcohol Flashcards
What are the three forms of alcohol?
- Isopropyl
- Methanol
- Ethanol (drinking alcohol)
What is the fermentation process?
- Sugar dissolved in water
- Yeasts multiply and convert sugar into ethanol and CO2
- Alcohol content about 10 - 15 %
- Fermented wines = extra alcohol
What is the distillation process?
- Fermentation –> Heated –> alcohol given off in vapor –> vapor cooled
- Alcohol content - 40 - 50%
Brandy = distilled wine
What is the main mode of administration?
- Oral
What is the absorption of alcohol like?
- Molecules cannot be ionized - pH levels have no effects upon absorption
- Readily dissolved in water & passes into blood from stomach lining, intenstines & colon
- 1st pass metabolism - alcohol dehydrogenase in stomach
What is the absorption rate and BAL affected by?
- Stomach contents
- Body fat (higher body fat means less water to dilute alcohol so greater concentrations)
- Medication
- Female sex (decrease in alcohol dehydrogenase, more body fat)
- alcohol concentration
- age
- usage (abstainers vs regular)
When the the BAL generally at a plateau
approx 1 hr after consumption
When is peak BAL?
approx 15 min after consumption (but depends when readings are take - after a few drinks levels reached sooner)
What drink types effect absorption
o Beer stays in stomach longer
o Absorption sparkling wines facilitated by carbination
o Higher concentration absorbed more quickly, up to a point ([~ 40 % alc.])
What is the expectance effect
Those who expect alcohol may have greater concentrations
What is the theoretical time course for BAL after single drink?
- A = Absorption Phase
- B & C = Plateau Phase
- D = Excretion Phase
What is the distribution of alcohol in body?
- Alcohol dissolves in water – distributed entirely in body water
- Crosses blood-brain barrier and placental barrier
- Circulates through lungs and vaporises in air (Breathalizer)
Where is alcohol excreted?
Some alcohol is excreted through breath,
sweat & urine
Most alcohol is metabolized in the liver (~90-98%)
– at rate ~ 1 SD/hr
How is alcohol metabolised by the liver?
- Alcohol is converted to acetaldehyde by alcohol dehydrogenase
- Acetaldehyde is converted into acetyl-coenzyme A
Acetyl-coenzyme A is then converted to water & CO2, via the Krebs cycle (or “citric acid cycle”)
What does having a genetic polymorphism in the kreb’s cycle mean?
Genetic polymorphism means they can’t break down acetaldehyde – can’t break down so often a protective factor
How does excretion vary between individuals?
- Excretion varies greatly between individuals
o Typical range ~ 10-20 mg/100ml/hr
What may affect the metabolism of alcohol?
- Rate of metabolism may depend on drinking experience
o Non-drinkers metabolize alcohol slightly slower - Eating speeds metabolism of alcohol – increases blood supply to the liver to speed up
What is the excretion of methanol and what are the effects of ingesting it?
- Excretion of methanol:
o Formaldehyde and formic acid
o Blindness and death if ingest methanol because of metabolites that lead to effects
o Ethanol treats methanol poisoning
What is the Microsomal ethanol-oxidizing system (MEOS)?
- Also responsible for metabolism of alcohol
- Increased activity with continuous drinking – thus heavy drinkers metabolize alcohol more quickly → metabolic tolerance
o Up regulation of MEOS system causes tolerance - Also responsible for metabolizing barbiturates → cross tolerance
o Used to be used similar the benzodiazepam
What are the interesting neuropharmacological traits of alcohol and what does this mean about alcohols site of action?
- Alcohol affects a variety of tissues
- Need a large dose to have an effect
- No drugs act as complete antagonists to all of the effects of alcohol
Therefore – conclude that alcohol does not work directly on specific receptor sites, but affects many sites of action
What is GABAA?
Inhibitory NT - GABBA-receptor-ionophor complex
Where are the sites of action of GABBA-receptor-ionophor complex?
Orthosteric & allosteric sites *– alcohol ¬ GABA effects (¯ neural activity) \ alcohol acts as a positive allosteric modulator
e.g. effects on cerebellum → inhibits pikinge neurons – causes stumbling and coordination
Where are the GABAB (metabotropic) receptors and what do they do?
May induce release of DA
- e.g., in VTA → less inhibition of DA release into NAcc
Inhibition of inhibition
How does alcohol affect 5-HT?
Alcohol stimulates 5-HT3 receptor (also important in releasing DA)
Where does ethanol bind and what does this mean?
- Ethanol binds to allosteric binding site – affects the ability to open ion channel
- Positive allosteric moderator because helps GABA ion channel to open – chloride flows in which hyperpolarizing it and inhibiting action potential
What is glutamate
an excitatory NT
How does alcohol effect Glutamate?
- Alcohol decreases functioning at NMDA receptor (blocks ion channel)
What does chronic exposure to acholol cause in terms of ion channels
Up-regulation of NMDA and glutamate
o Contributes to withdrawal effects of alcohol
- Hippocampus (NDMA receptors) and
o Memory consolidation – accounts for alcohols effect on memory
- PFC (glutamate and GABA neurons) – inhibits the brain and especially prefrontal cortex which leads to disinhibition – may say or do things wouldn’t otherwise do
What other things does alcohol effect?
- Second messengers
- Monoamine oxidase
- Glycine
- Acetylcholine
- Endogenous Opiod Systems
What are alcohol’s effects on the body?
Dilation of blood vessels - flushing (but decreased body temp)
- Increased urination
What are alcohol’s effects on sleep?
- Induces sleep, but does not increase total sleep time
- Decreased REM (1st part of sleep at low doses, whole night at higher doses, tolerance ~ 3 days)
o Important for memory consolidation - REM rebound effects upon cessation
- Body develops tolerance to alcohols effects on REM quickly because body needs it
What is alcohol’s effect on perception?
- At high doses, decreased absolute and difference thresholds for vision
- Decreased visual acuity (~0.7 BAC)
- Lowered peripheral vision
- Decreased sensitivity to smell, taste and pain (~0.07 – 0.08 BAC)
What are the subjective effects of alcohol?
- Biphasic effect re time and dose – but not for everyone
- Stimulant-like effects may ~ greater risk of abuse
What are alcohol’s effects on performance?
- Increased (slowed) reaction time
- Decreased hand-eye coordination (cerebellum)
- Decreased speed and accuracy
- Decreased vigilance
- Decreased memory (storage and retrieval)
o En bloc blackout
o Grayout - Decreased sensitivity of organs in the inner ear responsible for balance (Romberg sway test for drink driving)
What are alcohol’s effects on behaviour?
- Disinhibition
- Talkative, excitable, cheerful
- Sleepy, unconscious
- Nausea, vomiting
What are alcohol’s effects on driving?
- Impairs driving performance ~ 0.05 – 0.08 (lower for many)
- Reflected in crash statistics – young people overrepresented in drink driving fatalities
What are the conditioned responses to alcohol?
- Reinforcing properties of alcohol are dose dependent
- Decreased shock avoidance
- Increased response rates that have been paired with shock
- Similar effects in humans – alcohol decreases effect of aversive stimuli
What are the discriminative properties of alcohol?
- Easy discrimination from saline
- Generalized to barbiturates
- Can be blocked by 5-HT3 receptor blockers and opioid receptor blocker (nalterexone) but not a dopamine D2 blocker
What is the self-administration tendency in animals?
- Rats will drink in small doses, unless forced consumption
- Deprived of food and water/or paired associations
- Generally, rats will self administer sporadically, with periods of abstinence
What is the self-administration in humans?
- Usually high consumption followed by abstinence
- Depends on:
o Culture
o Gender
o Age
o Availability
What is the acute and selective tolerance of alcohol?
- Occur while still drinking – esp. to the subjective feeling of intoxication
What is the chronic tolerance to alcohol?
- Develops very quickly, within weeks for humans
- Does not develop equally for all effects
What is the metabolic tolerance of alcohol?
- Stimulation of alcohol dehydrogenase and MEOS
What is the conditioned tolerance for alcohol?
- Hypothermic Effects
- Environmental Tolerance
What is Early Minor Syndrome?
- Can occur whilst still drinking but usually within 8-12 hours
- Agitation, tremors, muscle cramps, vomiting, nausea, sweating, dreams etc
- Usually over < 48 hours
What is Later Major Syndrole
Delirium tremors (DTs)
- 2 days of minor symptoms followed by disorientation, confusion, hallucinations & seizures
- Lasts 7-10 days
- Can cause death if not managed (usually with anxiolytics &/or antipsychotics)
What is the therapeutic index of alcohol?
Low - 3.3
What is alcohol poisoning?
.3 - .4 = unconsciousness
.5 = death from respiratory failure <1-2 hours
What are the dangers to do with hangovers?
Dangerous with epilepsy, heart disease or diabetes
What are the socio-cultural harmful effects of alcohol?
- Accidents
- Relationships
- Finances
- Criminal Behaviour
What are the acute harmful effects on reproduction?
Small doses - inhibition
Large doses - sexual arousal
What is the chronic harmful effects on reproduction?
Loss of interest in sex
Impotence; shrinking testes
Menstrual dysfunction
Spontaneous abortion
What is foetal alcohol syndrome?
Cognitive impairments, poor coordination, ¯ birth weight, facial characteristics, malformed organs
What are the harmful effects on the liver?
- Hepatitis
- Cirrohosis
- Immune functioning
What are the harmful effects on the nervous system?
Korsakoff’s syndrome – thyamine definiency – treatable through B1 injections
Epilepsy
Dementia
Peripheral neuropathy
What is the effect on cancer and what makes this worse?
- Mouth, throat and liver cancer
- -> Even greater increased risk with smoking
What are the effects on heart disease?
- Alcoholic cardiomyopathy
What are the pharmacotherapies for alcohol dependence?
Disulfiram (Antabuse) blocks aldehyde dehydrogenase Acamprosate (Campral) ¯ glutamate activity Naltrexone Opioid receptor antagonist