Term
| What is the major way EtOH is different than most other meds? |
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Definition
| One of which is the social acceptance of low or moderate levels of consumption. Perhaps even having benefits while taken in moderation. However, there are still up to 30% of adults who do not drink. Conversely about 4 % of adults have defined alcohol dependence with another 4-5% having alcohol abuse which may not be biologically driven. |
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Term
| Do most people who abuse EtOH seek treatment? |
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Definition
|
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Term
| how do you define EtOH dependence? |
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Definition
a person's maladaptive pattern of alcohol use leads to clinically important distress or impairment;
3 of the following in a 12-month period:
Tolerance;
Withdrawal;
More time or larger amounts than desired;
Desire or effort to cut down;
Time spent obtaining or recovering;
Social, occupational or recreational effects;
Drinking despite consequences |
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Term
| In what ways can EtOH be considered a chronic disease? |
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Definition
Alcoholism is often compared to traditional illnesses:
Asthma, diabetes, heart disease and arthritis:
Progressive, relapsing disease;
Genetic factors are important;
Symptoms show with advanced disease;
Treatment requires lifestyle changes |
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Term
| What are the clinical components of EtOH? |
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Definition
Withdrawal (acute and subacute);
Tolerance;
Social devastation;
Medical consequences;
CNS – depression, cognition;
Non-CNS – liver, heart, renal, PNS, pancreas, etc |
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Term
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Definition
Brief therapies ;
Self-help groups (AA, ACOA, etc.);
Individual therapy;
Family therapy;
Psychoeducational activities;
Hypnosis;
Activities therapy;
Group therapy (elder specific);
Psychopharmacology |
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Term
| how does EtOH work in the brain? |
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Definition
| Alcohol acutely stimulates and chronically disrupts brain reward pathway |
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Term
| what is different about alcoholic brains? |
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Definition
| Alcoholics get much more stimulated and get much more rewarded when drinking. Normal people will feel euphoric after 1 drink and tired after 5 drinks. Alcoholics will feel ephoric after 5 drinks |
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Term
| What type of celular components seems to be targets for EtOH? |
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Definition
| Certain kinds of ligand-gated ion channels (i.e., postsynaptic receptors) appear to be an important target for ethanol action |
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Term
| How does the brian region model differ for addicted vs. nonaddicted brains? |
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Definition
| in addicted brain, there is a suppression of negative events. memory is over represented. Salience is much higher. When presented with a cue which can include the actual item (food, alcohol, sex, etc) or an associated memory (person, place or thing); the cue creates a salience factor. This is clearly influenced by memory and can drive behavior. That drive though also has certain controls that may override the drive. Memory in this instance is hippocampal in nature, salience and drive are likely derived in the ventral tegmental and accumbens, and control in medial dorso-lateral prefrontal cortex. |
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Term
| What makes a relapse inevitable? |
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Definition
| repeated rewards lead to increased salience as stored in the memory. Cues again provide stimulus for craving or reward. The frontal lobe is responsible for registering the conflict between the cue and the possible consequences of use. Without the conflict registration (stop signal) relapse is inevitable |
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Term
| What is an example of an antagonist? |
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Definition
| naltrexone for opiod dependence |
|
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Term
| what is an example of an anti-craving drug? |
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Definition
| acamprosate for alcohol dependence |
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Term
| what is an example of a cognitive enhance? |
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Definition
| modafinil for cocaine dependence |
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Term
| what is an example of an agonist? |
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Definition
| methadone, for opiod dependence |
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Term
| What can you treat for EtOH dependence? |
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Definition
Alcohol dependence:
Naltrexone;
Acamprosate;
Antabuse; |
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Term
| What can you treat for Opioid dependence? |
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Definition
Opioids
Buprenorphine
Methadone |
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Term
| What can you treat for cocain dependence? |
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Definition
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Term
| What can you use for nicotine abuse? |
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Definition
Nicotine:
Nicotine replacement;
Bupropion;
Verenicline |
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Term
| How does naltrexone work? |
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Definition
| it is a mu receptor blockade. Animal studies show that mu opioid receptor antagonists such as naloxone and naltrexone attenuate ethanol consumption c.f. . Further, ethanol’s pharmacological effects interact with mechanistic processes associated with opioid production, secretion, and binding . Naltrexone’s ability to reduce ethanol intake is negatively correlated with baseline -endorphin levels . |
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Term
| How does naltrexone fuction |
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Definition
| Functions as an opioid receptor antagonist (mu >> delta or kappa) |
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Term
| WHO DOES naltrexone work well for/ |
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Definition
| Family history is usually a very strong negative predictor of treatment response as demonstrated on the far right. However, naltrexone seems to substantially improve response in these patients to the point of response rates typically seen in low risk patients. |
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Term
| What is the human mu opiod receptor gene made of? |
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Definition
| OPRM1 gene is estimated to span at least 90 kb in the chromosome 6q24-25 region. Four coding exons are separated by 3 introns. |
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Term
| Who does Nalozone work best for? |
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Definition
Asp40 allele frequency of 13-20% (24.3 – 36% of European Americans have at least one copy).
Functional Significance:
Asp40 variant binds beta-endorphin and activates G- protein coupled protein potassium ion channels with 3 times greater potency ;
Naloxone challenge alters CRF secretion in those with the Asp40 variant;
Asp40 variant appears to be transcribed less efficiently than Asn40;
Asp40 increases pain sensitivity |
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Term
| What does having the G allele give you? |
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Definition
| less transcription of mRNA, less translation to protein (so less binding), less response to agoinst therapy in vitro, less pupulary dilatation related to agonist exposure |
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Term
| What does the increased use of antagonist do for cortisol levels? |
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Definition
| it decreases them in G and A allele subjects. |
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Term
| Is there a genetic influence? |
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Definition
4-fold increased risk in close relatives (e.g. children, siblings);
Identical vs fraternal twins;
Adopted away children still have a 4-fold increase in risk |
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Term
| what is the relationship between genetic polymorphisms and EtOH Tx? |
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Definition
| almost all tx variability can be explained by genetic variation |
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Term
| Who should be given Naltrexone? |
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Definition
Prior treatment failure;
High level of interest in biomedical therapies;
Low level of interest in traditional psychosocial therapies;
Cognitive impairment;
In most alcohol-dependent patients;
Consider depot formulation for added adherence |
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Term
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Definition
| a glutamate antagonist, an excitatory neurotransmitter, a NMDA antagonist, which reduces the intesity of post-cessation EtOH craving on exposure to high-risk drinking situation. For instance, acamprosate: a) suppresses conditioned cue responses to alcohol , which can occur even after prolonged periods of abstinence ; b) reduces the aversive effects of alcohol withdrawal related to increased glutamate and decreased central dopamine (DA) levels, particularly in the nucleus accumbens , and c) inhibits neuronal hyperexcitability and the expression of brain c-fos, an immediate early gene associated with alcohol withdrawal . |
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