Midterm 2 Flashcards
Summarize the absorption process for alcohol
What factors affect absorption?
Slow in stomach, fast in intestine
Molecules are unionized, pass membrane easily
Speed of absorption depends on gastric emptying
Concentration dependent diffusion
Affected by: having food in stomach, sex, ethnicity, age, drinking history, medications
Summarize the distribution process for alcohol
What factors affect distribution?
More body water = lower BAC
Females have less body water
Sex, age
Summarize the Metabolism/Elimination process for alcohol
What factors affect Metabolism/Elimination?
First pass in liver
Zero-order elimination (steady rate)
Breakdown by MEOS - enzyme, 5-10%
Affected by: age, ethnicity, drinking history, eating
What neurotransmitters does alcohol affect?
Dopamine, GABA, Glutamate, Opioids
What GABA receptor does alcohol bind to? What effect does it have?
GABAa
Positive allosteric modulation: enhancing inhibitory effects of GABA
By increasing the frequency + duration of the Cl- channel opening and decreasing channel closing
What are the effects of alcohol on GABA pathways?
Positive reinforcement of DA reward pathway
Inhibits regions of PFC: deficits in decision making (hypofunction)
Inhibits cerebellum: loss of balance, coordination, motor control
Inhibits subcortical regions: changes in cognitive arousal, attention, memory, mood
What glutamate receptor does alcohol bind to? What effect does it have?
NMDA
Antagonist effect, decreases excitation
Alcohol binds within the ion channel, blocking the central pore
What effect does alcohol have on Glutamate receptors?
Inhibits PFC: Impulsivity, impaired control (hypofunction)
Inhibits cerebellum: Interferes with memory formation and neurogenesis
Inhibits subcortical regions
What effect does alcohol have on Opioid receptors?
Indirect effect
Peptide precursor: causes B endorphin release from the pituitary and hypothalamus
What effect does alcohol have on Opioid receptors?
Enhanced drug liking and pleasure
Increased B endorphin release + binding in NAcc
Met-enkephalin + dynorphin increase in NAcc
How does alcohol affect the DA pathway?
Increased GABA activity or decreased GLu activity increases the amount of DA in reinforcement pathway
Decreased GLu increases DA in mesocortical pathway
What is RO 15-4513? Describe its properties and effects
Synthesized drug by Hoffman-Laroche
Competitive antagonist to alcohol on GABAaR
Would RO 15-4513 be suitable to treat alcohol abuse disorder? Why/Why not?
Does not block lethal effects of alcohol
Can cause convulsions
Are there any benefits to alcohol consumption (behavioural or otherwise)?
LOW consumptions in older people: reduce relative risk of coronary heart disease, heart attack, diabetes, stroke, reduced blood clotting
What is a gamma alcoholic?
An alcoholic that cannot control their drinking and is physically dependent
Indicated by high levels of tolerance and withdrawal
What is a problem drinker according to Jellinek?
A person who drinks increasingly heavily and experiences frequent blackouts
How do non-alcoholics progress to gamma alcoholics?
Moderate-social drinking increases consistently, increasing until tolerance and withdrawal make them dependent
How might expectation impact the effects of alcohol?
The perceived effect of alcohol consumption may lead to increased drinking
_____ brought wine to the UK
_______ brought by irish settlers
Romans
Distillation
What is the temperance movement?
Did it work? (USA/CAN)
The push against drinking and alcohol consumption
USA: yes due to religious ties
CAN: yes, not as successful
At what levels does alcohol act as a stimulant?
Low to mid consumption - 50-150mg/100ml
At what levels does alcohol act as a depressant?
Mid to high consumption - >150-290mg/100mL
What is the lethal dose of alcohol?
Depends the person
For alcoholics it could be as high as 360mg/100mL
Generic name
Amytal, Nembutal, Luminal, Librium, Xanax, Ativan, Valium, Rohypnol, Rivotril/Klonopin, Lunesta, Ambien, Buspar
Amobarbital, Pentobarbital, Phenobarbital, Chlordiazepoxide, Alprazolam, Lorazepam, Diazepam, Flunitrazepam, Clonazepam, Eszopiclone, Zolpidem, Buspirone
Drug class
Amytal, Nembutal, Luminal, Librium, Xanax, Ativan, Valium, Rohypnol, Rivotril, Lunesta, Ambien, Buspar
Barbiturates: Amytal, Nembutal,Luminal
Benzodiazepines: Librium, Xanx, Ativan, Valium, Rohypnol, Rivotril
Z drugs: Lunesta, Ambien,
Other: Buspar
Main effects of Barbiturates?
Licit use?
Muscle relaxation, lowered respiration/BP/heart rate, decreased time in REM and deep sleep
Short term insomnia, anxiety, seizures
Main effects of Benzodiazepines?
Licit use?
Muscle relaxation, anticonvulsant properties, increased appetite/weight gain, reduced sleep latency/night time awakening/time in REM/deep sleep, increased total sleep time
Insomnia, anxiety, epilepsy, panic disorder
Main effects of Z-drugs?
Licit use?
Psychomotor impairment, reduced sleep latency/night time awakening, increased total sleep time
Insomnia
What is the main licit use of Buspirone?
Treatment of GAD
Summarize the neuropharmacology (binding and effect) of barbiturates
Barbiturates bind to GABAa receptor as positive allosteric modulators
They increase the inhibitory effects of GABA by opening the Cl- channel into cell + hyperpolarizing cell
Which drugs (barb/benzo,z drug) have the highest abuse potential?
How do we know?
Short acting barb.
Anxiolytics that target a1
From self-administration tests and behavioural conditioning
What effects are common between barb., benzos, z drugs?
Psychomotor impairment
What are 2 specific memory effects of benzos?
- Anterograde amnesia (new info aquisition)
- Impaired implicit memory (task performance)
Amytal - generic, street, class, speed, illicit use
Amobarbital
Blues/Blue heaven/Blue devils
Barbiturate
45min-1hr
Truth serum
Nembutal - generic, street, class, speed, illicit use
Pentobarbital
Yellow jackets/mexican yellow
Barbiturate
20-60 mins
Suicide/Euth
Luminal - generic, street, class, speed
Phenobarbital
Purple hearts/goof balls
Barbiturate
5-30 mins
Valium - generic, street, class, speed, illicit use
Diazepam
Eggs/Chill pills/Vallies
Benzodiazepine
15-60 mins
Euphoric effects
Rohypnol - generic, street, class, speed, illicit use
Flunitrazepam
Date rape/roofies
Benzodiazepine
15-20 mins
Date rape use
Klonopin/Rivotril - generic, street, class, speed
Clonazepam
K/K-pin/super valium
Benzodiazepine
30-60 mins
Librium -generic, street, class, speed, illicit use
Chlordiazepoxide
Candy/Downers/Tranks
Benzodiazepine
15-30 mins
Self medication
Xanax - generic, street, class, speed, illicit use
Alprazolam
Xan/Xannies/Footballs
Benzodiazepine
10mins - 1hr
Euphoric effects
Ativan - generic, street, class, speed, illicit use
Lorazepam
Candy/Downer/Tranks
Benzodiazepine
20-30min
Date rape/self medication
Lunesta - generic, street, class, speed, illicit use
Eszopiclone
Sleepers/Zombies/sleep-easies
Z-drug
< 1hr
Sedative effects
Ambien - generic, street, class, speed, illicit use
Zolpidem
R2/Roche/Roofies
Z-drug
30mins - 1hr
Euphoria, reward path
BuSpar - generic, class, licit use
Buspirone
OTHER drug
Treatment for GAD
How does alcohol affect self administration in animals and humans?
Reinforcing effect, lowered threshold for ICSS paradigm
What are the acute effects of alcohol?
Hangovers
Withdrawal effects: sensitivity, rebound excitation
Reproductive effects: increased erection time, reduced genital arousal in female bodies
What are the chronic effects of alcohol?
Brain damage
Liver damage
B1 deficiency
Heart disease
Fetal alcohol syndrome
Alcohol use disorder
What are the NPI treatments for alcohol addiction?
Abstinence
Harm reduction
Contingency management (positive reinforcement)
The popularity of chewing tobacco in the USA can be contributed to what?
The rejection of European ideals and the independence from the crown
What are the different routes of administration for nicotine?
List them by peak time
Inhalation: 7-15min
Intranasal: 10min
Buccal/Sublingual: 20-35min
Transdermal: 4hr
Where does the most nicotine breakdown occur? What happens to it?
In the liver
Breakdown by CYP2A6 enzyme to produce inactive metabolite
How do history, sex, pregnancy, age, food, menthol, genetics, and ions make nicotine elimination variable?
History: non smokers produce fewer enzymes
Sex: female bodies clear nic faster
Preg: faster elimination
Age: slowed in older people
Food: full stomach speeds elimination
Menthol: Inhibits enzyme
Genes: fast vs slow metabolizers
Ions: >7 increases nic reabsorption
Is nicotine reinforcing? Why/Why not?
Yes
Direct stimulation of DA reward path in NAcc
Indirect stimulation (excitement) of GLu release onto DA neurons in VTA and NAcc
What are the risks of nicotine consumption/use?
Cancer
Cardiovascular disease
COPD - lungs
Reproductive issues
Nic poisoning
What are the pharmacotherapy treatments for nicotine addiction?
Replacement therapy: use different source of nic, gradual weaning
Bupropion: reduce reward effect
Varenicline: partial agonist on DA pathway, more likability
What is mecamylamine? How does it act? How/Why would you use this in discrimination?
A drug with an antagonist effect on the neuronal nAChRs
If a stimulating property of nic can be blocked using it, it indicates the effect was a result of action on nAChRs
What risks does smoking / nicotine have for children?
Miscarried, premature, ill babies
Nicotine poisoning from ingested products
Leukemia, Lymphoma, brain cancer
SIDS
Secondhand and thirdhand smoke
What are mainstream, sidestream, thirdhand smoke?
Mainstream: the smoke exhaled by the smoker
Sidestream: released from the cig between puffs
Thirdhand: the tobacco’s toxic particles that land and stay on surfaces
How do addiction models explain the need to smoke?
Constant level: attempt to avoid withdrawal and maintain constant level of nic in system
Increased reinforce: attempt to reach highs of nic in brain
Dual-reinforce: Sensory experiences / cues acquire reinforcing properties for smoking
What is the constant level theory? What study supports this?
The theory that people smoke to maintain a constant level of nicotine in their system to avoid withdrawal symptoms
Study: 50% of smokers light up within 30mins of waking
What is the Bolus + Increased Reinforcement theory? What study can support this?
The theory that people smoke because of the pleasurable and reinforcing effects of a fast-high dose of nicotine
Study: disproved - no spike in brain nicotine, but an increase in the concentration that never falls before next puff
What is the Dual-Reinforcement theory? What study can support this?
The theory that people continue smoking because the cues associated with it become secondary reinforcers
Study: nicotine enhances the effect of weak reinforcers
Summarize the limitations the have impacted nicotine research
Design flaws/ shortcomings that make interpreting results difficult
Lack placebo/control
Lack double blind
Expectancy and bias cannot be ruled out
What are the acute effects of nicotine? How does blood plasma relate to this?
Pleasure
Rush/Buzz/High
A study showed that maximal ratings of “high” occur as levels of nic in blood plasma increase
Summarize the effects of nicotine on B2 receptor subunit
Increased DA activity in NAcc when VTA is stimulated + self-admin nic normal dose. Improved cognitive function & exploratory behavior
Summarize the effects of nicotine on the a5 receptor subunit
Mediation of aversive effects of high nic levels
Reduces self-administration in response to negative effects
How was drug discrimination used to determine the NT involved in the effects of alcohol?
Using:
Serotonin receptor blockers
Opioid receptor blockers
Positive GABA modulators
GLu receptor blockers
How does alcohol affect perception?
How do can test this?
Lowered: visual accuracy, peripheral vision, sensitivity to taste/smell, pain sensitivity
Critical flicker fusion test
How does alcohol affect sleep? In non-alcoholics and in chronic users
Non-alc: sleep aid, improved quantity and quality, REM rebound brings wakefulness
Chronic: difficulty falling asleep, severe insomnia, altered sleep patterns
How does alcohol affect memory? In low and high quantities
How can we test this?
Low-Mid: affect attention, encoding, retrieval of info, storage of info
High: additional impaired accuracy of verbal memory, blackouts
Memory scanning tests
How does alcohol affect motor performance?
Slows reaction time
Decreased response speed and accuracy
Poor hand-eye coordination
Poor balance
How does alcohol affect driving ability?
Poor reaction time
Poor error monitoring
Poor orientation
How does alcohol affect disinhibition/behaviour control?
Increased impulsivity
Improved performance in mild-anxiety-inducing tasks
What effects does alcohol have on the body in low and high quantities?
LOW: Flushed skin (dilated capillaries), Temporary warmth
HIGH: Rapid heat loss
BOTH: inhibits antidiuretic hormone - increased urine + water loss
