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88 Cards in this Set

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Alcohol abuse increases the risks of ?
Cancer
Domestic Violence
Injury
Sexual assualt
MVA's
Relative cost of alcohol abuse to all other drugs?
1.5x higher than all "other" drugs.
Characteristic responses to alcohol in order
Euphoria/anxiolysis
Impaired thought processes
Impaired coordination
Sedation
0.02-0.03 g/dL blood alcohol has the effects of.....
Mood elevation
Slight muscle relaxation
0.05-0.06 mg/dL
Relaxation and Warmth, Increased reaction time, Decreased fine muscle coordination
0.08-0.09
Euphoria
Impaired balance
speech
vision
hearing
muscle coordination
0.14-0.15
Gross impairment of physical and mental control
0.20-0.30 g/dL blood alcohol level results in...
Severe intoxication
Very little control of mind or body
0.40-0.50 g/dL blood alcohol levels have the effect of
Unconscious
Deep coma
Death from respiratory depression
Genetics contribute to about what percentage of alcoholism risk?
60%
The receptors responsible for euphoria/pleasure from alcohol consumption are
Dopamine receptors
Opioid receptors
Anxiolysis/ataxia alcohol receptors?
GABA
Sedation/amnesia alcohol receptors?
GABA
NMDA
The alcohol receptors responsible for nausea are....
5HT3
Stress alcohol receptors?
CRF
5HT
NE
Receptors causing alcohol neuroadadaptation?
GABA
Glu
5HT
Dopamine
Etc.
Receptors causing alcohol withdrawal?
GABA
Glu
Dopamine
NE
How does alcohol affect neurotransmitter processes?
Direct interactions with receptors or channels.
-allosteric activation
-allosteric inhibition

Indirect interactions with processes that modify receptor activity
-neurotransmitter release
-receptor function
Effects of long term alcohol use?
Cognitive and motor dysfunction.

Problem solving deficit
Short term memory loss
Wernicke-Korsakoff’s syndrome
Visuospatial ability impairment
Balance and postural stability loss
Upregulation of which receptors occurs in long term alcohol abuse?
Glutamate
Ach
Downregulation of which receptors occurs in long term alcohol abuse?
Serotonin
GABA
Alcohol use limits for men ?
<15 standard drinks per week
<5 standard drinks per occasion
Alcohol use limits for women and elderly?
<8 standard drinks per week
<4 standard drinks per occasion
Amount of alcohol in 1 standard U.S drink?
14g
What is the mechanism of action of Disulfiram (antabuse)?
Blocks acetaldehyde metabolism
What does Acamprosate (Campral) do....
Reduces craving in abstinent alcoholics by unknown mechanism.
Naltrexone
Opiod antagonist that reduces rewarding effect in abstinent alcoholics
Topirimate (topamax)
Anticonvulsant which is the only drud that reduces cravings in ACTIVE alcoholics.
Odansetron (Zofran)
5HT3 antagonist
anti-emetic which reduces cravings in EARLY ONSET alcoholics.
Women are more sensitive to the subjective effects of ethanol because of....
Lower body-water content

Reduced first-pass metabolism
Substance dependance is 3 or more of what criteria?
Tolerance
Withdrawal
Substance use more or longer than intended
Persistent desire or unsuccesful efforts to cut down.
Much time spent in activities related to use.
Give up other activities to use substance
Use continues despite physical or psychological problems due to use.
CAGE questionaire?
Cut down
Annoyed
Guilt
Eye-opener
Comorbidities of substance abuse?
Schizophrenia
Major anxiety disorder
Major depressive disorder
Estimated cost of drug abuse compared to other brain diseases?
2x
Highest substance comorbidity with major depression?
Opiates
Highest substance comorbidity with antisocial personality?
Alcoholism
3 reasons for the high comorbidity between psychiatric disorders and substance abuse?
Disorder Fostering Disorder (self-medication model).

Overlapping Neurobiological Pathways (kindling model).

Underlying Genetic Factors.
Signs of drug abuse include?
Failure to fulfill responsibilities (school,work, family);

Recurrent use in hazardous situations (driving, using machinery);

Recurrent legal problems related to substance use;

Continued use despite social and interpersonal problems.
Host factors related to beginning or continuing a pattern of substance abuse?
Heredity
Drug Metabolism
Psychiatric symptoms
Prior experience
Risk-taking behaviors
Risk of addiction in descending order as a percentage?
Nicotine
Heroin
Cocaine
Alcohol
Stimulants
Cannabis
Analgesics
Three or more of the following constitute substance abuse as per the DSM IV?
More than intended

Failed efforts to stop

Time spent acquiring or using

Frequent intoxication or withdrawal

Abandonment of activities because of use

Continued use despite effects on life

Tolerance

Frequent use to relieve withdrawal.
Right shift of the effect vs. dose curve is called?
Tolerance
Left shift of the effect vs. dose curve is called?
Sensitization
Barbiturates have fallen out of favor because tolerance leads to?
A decreased (narrow) therapeutic index and increased risk of toxicity.
Innate tolerance in the context of substance abuse refers to?
Genetically acquired tolerance
What are the three types of acquired tolerance?
Metabolic (pharmacokinetic)

Functional (pharmacodynamic)

Learned (behavioral tolerance)
Positive reinforcement
Presentation of a desirable stimulus.
Negative reinforcement
Removal of a desirable stimulus
Positive punishment
Presentation of an undesireable stimulus.
Negative Punishment
Removal of an undesirable stimulus.
What are three pharmacological approaches or principles that can be used in drug withdrawal?
Cross dependance
Antagonists
Aversive agents
Schedule 1
No accepted medical use.
High abuse potential.
Eg. heroin, marijuana, LSD, MDMA
Schedule 2
Some therapeutic uses.
High abuse potential
Eg.cocaine, methylphenidate, amphetamine, morphine, codeine, oxycodone, methadone, pentobarbital
Schedule 3
Some therapeutic utility.
Lower abuse potential than Schedule 2
Eg. Nalorphine
Schedule 4
Some therapeutic utility.
Lower abuse potential than Schedule 3
Eg. chlordiazepoxide, diazepam, midazolam, phenobarbital
Schedule 5
Very limited abuse potential
Eg. Buprenorphine
Brain circuits affected or that play a role in drug abuse and addiction.
Prefrontal cortex
Anterior cingulate gyrus
Orbitofrontal cortex
Subcallosal cortex
Nucleus accumbens
Ventral pallidum
Hippocampus
Amygdala
Drugs of abuse usually target which two brain signalling pathways?
Dopaminergic and seratonergic.
Seratonergic pathways in the context of substance abuse have to do with the functions of ?
Mood
Memory processing
Sleep
Cognition
Dopaminergic pathways in the context of substance abuse have to do with the functions of?
Reward (motivation)
Pleasure (euphoria)
Motor function (fine tuning)
Compulsion
Perseveration
How long before a therapeutic dose of Morphine can induce dependance?
About two weeks.
Opiate tolerance mechanism is predominantly?
pharmacodynamic
(NOT pharmacokinetic/Met.)
Symptoms of opioid withdrawal symptoms.
Craving
Restlessness
Irritability
Pupillary dilation
Increased pain sensitivity
Sweating
Nausea
Cramps
Vomiting
Diarrhea
Muscle aches
Piloerection (“gooseflesh”)
Fever
Increased blood pressure, Yawning
Insomnia
Anxiety
Tolerance mechanism for Barbiturates is?
pharmacokinetic and pharmacodynamic
Tolerance mechanism for benzodiazepines is?
primarily pharmacodynamic
Shortest period that can induce withdrawal symptoms from benzodiazepines?
1 week
The #1 class of “abused” prescription drugs ?
Anxiolytics (mostly benzodiazepines)
BZDP withdrawal symptoms
-Moderate dose use-
Anxiety
agitation
Increased sensitivity to light and sound
Paresthesias
Strange sensations
Muscle cramps
Myoclonic jerks
Sleep disturbance
Dizziness

-High dose usage-
Seizures
Delirium
BZDP withdrawal options
Pentobarbital or phenobarbital (t1/2 = 90 hrs) can be given orally.

Substitute long acting for short acting agent.
BZDP antagonist
Flumazenil
Treatment options for alcohol addiction?
AA
Benzodiazepines: oxazepam (short-acting) or chlordiazepoxide and diazepam (longer half lives).
Phenobarbital (half-life ~ 90 hrs)
Naltrexone
Acamprosate - competitive NMDA antagonist
Disulfiram (antabuse)
Mechanism for cocaine and amphetamines?
Dopamine reuptake inhibition
The half life of Cocaine is?
t1/2 = 40-50 min
What is the half life of Amphetamine?
t1/2 = 10 hrs
Side effects of cocaine and amphetamine.
Increased HR and BP
Cardiac irritability
Involuntary motor movements Stereotyped behavior
Paranoia and irritability
Hypertensive crisis Intracerebral hemorrhage Convulsions
Hyperpyrexia
Respiratory depression
The urine metabolite of Cocaine and Amphetamine is...
Benzoylecgonine.
Formed after hydrolysis of the two esters.
Present 2-5 days after a binge.
Which drug exhibits sensitization or a left curve shift ?
Cocaine
What non FDA approved treatments may be useful for treating cocaine addicts?
Antidepressants (desipramine)

Modafinil (PROVIGIL) - adrenergic stimulant approved for treatment of narcolepsy

Disulfiram (ANTABUSE) - mechanism for reducing cocaine use is unknown (may be related to decreasing alcohol use and/or to increasing aversive effects of cocaine)

Propranolol - ß-blocker; reduced relapse in clinical trial

Enhance GABA neurotransmission: Topiramate (TOPAMAX), baclofen (LIORESAL)

Naltrexone - effective in relapse prevention.
Varenicline
Partial agonist at nicotine receptors.
What type of drug is Rimonabant (Acomplia)?
Cannabinoid receptor antagonist (Non-FDA approved)
What is Amantadine?
Endogenous Ligand for cannabinoid receptors.
Predictive animal model
Does not resemble the disease in terms of etiology or symptomatology, but is predictive of clinical outcome
Isomorphic animal model
Resembles the disease in terms of symptoms and predictive outcome, but is artificially produced in the lab
Homologous animal model
Resembles the disease in etiology, symptomatology, and predictive outcome.
Best drug dependance animal models.
Drug self administration models.

Determine whether drug presentation maintains behavior above control levels.
Nicotine creates reward by stimulating...
Direct release of dopamine in the nucleus accumbens.

Also releases glutamate to a greater extent than GABA which causes more dopamine release.
Questions for nicotine addiction.
Do you smoke more than a pack a day?

Do you smoke 30 minutes or less after you get out of bed?

Have you ever had withdrawal symptoms?
Varenicline (chantix)

Buproprion

What are they and how do they work?
Smoking cessation drugs.

Chantex is Ach agonist/antagonist

Wellbutrin (Zyban) works on dopamine in nucleus accumbens