Week 7.4 Flashcards
Why is tolerance clinically important?
- acute tolerance predicts development of alcoholism
- chronic tolerance maintains abuse
- increases risk of complications
- increases cross-tolerance of depressant drugs
The most abused drug in America is ___.
marijuana
How did the 2010-2012 crackdown on painkillers affect opioid-related deaths?
it increased them as more people turned to heroin instad
Earlier in life, one’s risk of addiction is more dependent on ___ than in adults.
familial environment
Later in life, one’s risk of addiction becomes more reliant on what factor?
genetics
What three classes of genes correlate with addiction?
- tolerance
- self-recognition of alcohol-related problem
- withdrawal and continued use despite problems
What personality trait correlates with addiction?
externalizing/impulsive phenotypes
What three social factors greatly influence or trigger a person’s genetic liability for addiction?
- peer interactions
- permissive parenting
- availability of substances
What kind of parenting style leaves genetically predisposed adolescents at greater risk for addiction?
a permissive parenting style
What is the relationship between addiction and impulsivity?
- early drug use affects development, causing more impulsivity
- impulsivity increases risk of continued use and addiction
Which DA receptors increase AC activity?
D1 and D5
What is the difference between drugs with a direct and indirect effect?
those with a direct effect act at synapses in the nucleus accumbens while indirect ones act outside the nucleus accumbens to influence activity within it
How does cocaine increase DA in the NA?
binding and blocking DAT
How do amphetamines increase DA in the NA?
competes with DA to be taken up by DAT, leaving more DA in the cleft
Why does amphetamine withdrawal cause a mood disorder?
because it replaces DA in synaptic vesicles, limiting future supply
What makes certain drugs a greater risk for abuse?
rapid onset/increase in DA (free base or IV)
Effects of acute stimulant use.
- behavioral activation
- cue conditioning and cue-induced craving
- psychosis
Effects of chronic stimulant use.
- aggression
- paranoia
- hallucinations
- delusions
- cognitive dysfunction
Complications of stimulant use.
- seizures
- vasoconstriction (ischemia and hypertension)
- pulmonary toxicity
- hepatotoxicity
- HIV
- sudden cardiac death
Withdrawal symptoms of stimulants.
- lethargy
- exhaustion
- irritability
- hunger
- poor concentration
- dysphoria and suicidal ideation
How is stimulant withdrawal treated?
tricyclics
How do opioids increase DA in the NA?
bind mu-receptors are presynaptic terminals in the VTA, reducing GABA release and disinhibiting the VTA
How does alcohol increase DA in the NA?
the same way as opioid receptors
What are the effects of chronic opioid use?
- analgesia
- euphoria, tranquility, anxiolytic
- respiratory depression
- diminished GI motility
- cough suppression
- nausea, vomiting, pruritis
Physical tolerance to opioids takes how long to develop?
4-6 weeks
Withdrawal from chronic opioid use is likely to last how long?
acute withdrawal for 7-10 weeks followed by subacute symptoms for up to a year
Early symptoms of opioid withdrawal.
- anxiety
- nausea
- pilorection
- yawning
- lacrimation
Late symptoms of opioid withdrawal.
- diarrhea
- abdominal cramps
- myalgia
- insomnia
- dysphoria
How do we manage opioid withdrawal?
- methadone detox
- reduce discomfort
What is buprenorphine?
a partial opioid receptor agonist with high affinity
Endogenous cannabinoids have what role?
- learning
- memory
- motivation
- reward
Where are cannabinoid receptors found?
- CB1 in the CNS
- CB2 in the PNS
Describe cannabinoids.
- lipids
- freely diffusable
- not stored
- retrograde messengers
How do cannabinoids induce reward?
inhibition of GABAergic input to the VTA
Effects of cannabinoid use.
- sensory amplification
- time distortion
- increased appetite
- perceptual distortions
- euphoria/relaxation
Why do cannabinoids have few withdrawal effects?
because they are lipid in nature and thus there is no shape decline in effects
Withdrawal symptoms of cannabinoid use.
- anxiety
- dysphoria
- insomnia
How does MDMA increase DA in the NA?
- inhibits vMAT, leaving NT in the presynaptic cytosol
- taken up by MAT and reverse MAT direction
What is serotonin syndrome?
side effects of MDMA
- confusion
- hyperthermia
- hyperreflexia
- myoclonus
- rhabdomyolysis
How does PCP work?
- NMDA receptor antagonist
- partial D2 receptor agonist
Acute effects of inhalants.
- dizzy
- drowsy
- disinhibited
What are the risk of inhalant use?
- drastically low BP
- sudden cardiac death
- neuronal deterioration
What are the six stages of change?
- precontemplation
- contemplation
- preparation
- action
- maintenance
- relapse
Alcohol is primarily absorbed where in the GI tract?
the duodenum
Peak BAC can be variable based on what factors?
- amount
- rate
- food composition
- gastric emptying
- gastric metabolism
- use of other medications
How does food consumption affect alcohol absorption/
it slows gastric emptying
Why do women achieve higher BACs then men?
- women have less total body water
- women have less gastric ADH activity
- men have a high liver volume and amount of ADH
How is ethanol metabolized?
- ethanol to acetaldehyde by alcohol dehydrogenase
- acetaldehyde to acetate by aldehyde dehydrogenase
Alcohol is primarily metabolized by what organ?
the liver
Alcohol dehydrogenase follows what order kinetics?
zero order, meaning that it is a linear rate
What is disulfiram?
an aldehyde dehydrogenase inhibitor prescribed to alcoholics to make them sick when they drink
What is the primary source of inter-individual variability in alcohol metabolism?
genetic polymorphisms in the alcohol metabolic enzymes
Which alcohol dehydrogenase allele is associated with higher metabolic rate?
ADH2*3
What aldehyde dehydrogenase allele is associated with asian glow?
ALDH2*2
How can alcohol increase a second drug’s effect when the two are taken together?
- synergistic depressive effects
- increase absorption
- comete for metabolic enzymes
Give an example of how alcohol can increase the toxicity of another drug.
induces higher expression and activity of MEOS (microsomal ethanol oxidizing system), which will convert acetaminophen to a toxic metabolite
How does alcohol interact with phenytoin?
- increase the effect by competing for metabolic enzymes
- decrease the effect by up regulating the metabolic pathway
What is tolerance?
decreased physiologic and psychologic effects of a drug with prolonged exposure to that drug
What is acute tolerance?
that which occurs during the time-course of a single exposure to that drug
What is chronic tolerance?
that which occurs with repeated and regular use of that drug
What are four reinforcing effects of alcohol?
- euphoria
- altered consciousness
- relief of anxiety
- relief off withdrawal
Name four effects alcohol has on NT systems.
- facilitates GABA transmission
- blocks NMDA
- activates the opioid system
- indirectly increases DA in the nucleus accumbens
The sedative effects of alcohol are mediated by which NT changes?
increased GABA and diminished NMDA signaling
Craving for alcohol is mediated by what NT change?
the diminishing opioid levels as the effects wear off
The eleven criteria for substance use disorder fall into what four categories?
- impaired control
- social impairment
- risky use
- physical dependence
__ grams of alcohol equal one drink.
14 grams
What qualifies as a “heavy drinker”?
5 drinks in a day at least weekly
When do women experience their peak weekly drinking?
between the ages of 50 and 59
Binge drinking rates are highest for which age group?
18-29
Which race experiences the most heavy drinkers?
northern europeans
What morbidities are highly associated with alcohol?
- industrial accidents
- suicide
- hospitalizations
- marital violence
- violent crime
The life expectancy of an alcoholic is __ years less than a normal individual.
15
__% of alcoholics will experience spontaneous remission
20
Alcohol decreases absorption of what substances?
folate, thiamine, B12
Alcohol increases absorption of what in the small intestine?
iron
What are the major complications of alcoholic cirrhosis?
- esophageal varicies and bleeding
- bleeding hemorrhoids
- encephalopathy
Why do many alcoholics suffer from anemia?
- blood loss (more instances, fewer platelets)
- hypersplenism
- decreased folate absorption
- direct toxic effect on erythropoiesis
What are the criteria for fetal alcohol syndrome?
- growth retardation
- altered mrophogenesis
- CNS involvement
What are the signs of CNS involvement in those with fetal alcohol syndrome?
- microcephaly
- irritability in infancy
- altered muscle tone
- poor coordination
- hyperactivity
- intellectual disability
What are the facial dysmorphologies commonly associated with FAS?
- flat midface
- short nose
- indistinct philtrum
- thin upper lip
How does acute alcohol use cause death?
respiratory depression
Alcoholics have a higher prevalence of which psychiatric illnesses?
- antisocial personality disorder
- depression
Describe alcoholic polyneuropathy.
- lower extremities more than upper
- distal more than proximal
- “burning feet” sensation
Alcoholic polyneuropathy is due to what?
vitamin B complex deficiency
What are the features of Wernicke’s encephalopathy?
triad of CN VI paralysis, truncal ataxia, and confusion
What brain structure is affected in those with Wernicke’s encephalopathy?
the cerebellum
What causes Wernicke’s encephalopathy?
thiamine deficiency (typically secondary to alcoholism)
What is Korsakoff’s syndrome?
the inability to retain new informaiton
How do we prevent the progression from minor alcohol withdrawal to major withdrawal?
with benzodiazepines
What are the symptoms of persistent alcohol withdrawal?
insomnia, anxiety, depression
What is a dry drunk?
someone in remission from alcoholism continuing to experience persistent alcohol withdrawal
What is central pontine myelinosis?
a possible CNS affect of alcoholism that results in quadriplegia due to rapid sodium correction
What is Bignami syndrome?
a syndrome of seizures, coma, and quadriparxsis due to demyelination of the corpus callosum often associated with red wine
How can alcoholic dementia be distinguished from Alzheimer’s?
alcoholic dementia will stop progressing with abstinence
What is considered “at risk drinking”?
level of consumption directly harmful or correlated with greater health problems
- more than 14 in a week or 5 in a day for men
- more than 7 in a week or 4 in a day for women
What are the CAGE questions?
- felt you should cut down?
- felt annoyed by criticism of your drinking?
- felt guilty about your drinking?
- eye opener?
Symptoms of early alcoholism?
- anorexia
- diarrhea
- palpitations
- insomnia
- impotence
- poor memory
What happens to MCV in alcoholics?
it increases due to folate deficiency
What liver enzyme values suggest alcoholic liver disease?
AST/ALT > 1, ALT<300
Who should receive brief alcohol use intervention?
at risk drinkers who don’t qualify for a diagnosis of alcoholism
What is the goal of alcohol use intervention?
moderate drinking
What are the elements of brief alcohol use intervention?
- feedback
- advice
- commitment
- tracking
How do we treat major alcohol withdrawal?
- supportive care
- benzodiazepines
- antipsychotics
What is naltrexone?
an opioid receptor antagonist that helps attenuate alcohol relapse
What is acamprosate?
a GABA agonist and NMDA antagonist that helps maintain abstinence
