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Term 5: Behavioral Science > 6/19- Alcohol/Substance Abuse 4: > Flashcards

6/19- Alcohol/Substance Abuse 4: Flashcards

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1
Q

What kind of drugs are used to treat alcoholism relapse prevention?

A

Opioid antagonists

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2
Q

What treatments (3) are used to treat nicotine dependence?

A
  • Varenicline
  • Selegiline
  • Nicotine vaccine
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3
Q

What is the priming effect?

A

Think: Lay’s potato chips

  • Once you start, it’s hard to stop; start craving more rather than satisfying the craving
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4
Q

What are the mechanisms for Naltrexone’s efficacy in the treatment of alcohol dependence?

A
  • Craving reduction
  • Modifying experience of intoxication
  • Inhibition of the priming effect of the initial drink
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5
Q

What is the process in which alcohol stimulates ___ receptors?

A

Opiate receptors

  • Alcohol raises beta endorphin, stimulating mu opiate receptors
  • Stop alcohol, beta endorphin drops and craving starts
  • Continued alcohol use or withdrawal starts
  • Alcohol raises…
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6
Q

How does Naltrexone alter the process in which alcohol stimulates opiate receptors?

A
  • Naltrexone raises beta endorphin
  • Alcohol can not raise BE
  • Relapse prevented
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7
Q

Which patients are more responsive to Naltrexone?

A
  • More complex and severely dependent patients may be better for naltrexone Genetics may play a role
  • Strong family history of alcoholism
  • Get biggest response in group that have > 50% of relatives with alcoholism
  • Genetic responsivity: mu opiate receptor polymorphism
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8
Q

What was found in the relative BE levels in sons of people with alcoholic fathers?

A
  • Much much lower levels than control
  • Lower even than the BE levels of someone who was abstinent after being alcohol dependent
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9
Q

How does B-endorphin level change after alcohol consumption in sons of alcoholics?

A

Get a significant raise for relatively small amount of alcohol

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10
Q

Comparison between family history positive and negative people on Naltrexone?

A
  • Left: half a glass of beer on placebo
  • Placebo did not have much effect on FH+
  • Right: 2 glasses of beer on Naltrexone
  • Response of FH+ group was normalized!
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11
Q

What are pharmacogenetics?

A

Effects of genetic polymorphisms on pharmacological effects of drugs or medications

  • Matching patients to treatments based on genetics
  • Personalized medicine
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12
Q

Mice without u opiate receptors will not do what?

A

Self-administer alcohol

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13
Q

What gene was found to be relevant for alcoholism and beta endorphin?

A

Human Mu opioid receptor gene

  • Can make normal levels of beta endorphin, but receptor is 3-4x more sensitive than normal
  • OPRMI1 gene sequence: 118 A -> G exon 1 SNP increases OPRMI affinity for BE
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14
Q

What gene was found to predict Naltrexone response in alcoholics?

A

Again, mu-opiate receptor involved

  • Asn40Asp variant
  • 24-36% of Europeans; associated with alcoholism in Swedes (accounting for 11% of inheritence)
  • Functional polymorphism -> 3x increase in beta endorphin binding to mu receptor
  • Best response (non-relapse) with polymorphism (95%)
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15
Q

What is an endophenotype?

A

Endorphin dependent alcoholism

  • Alcohol -> increase in endogenous opioids
  • Euphoria/stimulation
  • Sensitive mu receptors
  • Family history
  • Alcohol craving
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16
Q

What are some strategies that have had limited efficacy for nicotine dependence?

A
  • Nicotine replacement therapies
  • Buproprion
17
Q

Best quit rates come with what treatment (early on)?

A
  • Both Buproprion and Nicotine patch seem to help the most
  • However, at a year, they’re all about the same (20%)
18
Q

Approved medications for treating nicotine addiction?

A
  • Nicotine patch, gum, lozenge, inhaler, spray
  • Buproprion (anti-depressant)
  • Varenicline (Chantix): partial nicotinic receptor agonist (a4B2 receptor)

(Nicotine vaccine promising; on the way)

19
Q

Most new drugs are what class? Mechanism?

A

Partial agonists

  • Agonists at low doses
  • Antagonists at high doses
20
Q

Nicotine stimulates what pathway?

Varenicline stimulates what?

A
  • Mesolimbic path (from VTA -> nucleus accumbens)
  • Same is stimulated by Varinicline; main action is at VTA (results in lesser amount of DA release from VTA at nAcc as well as prevention of nicotine binding at the a4B2 receptors)
21
Q

T/F: Varinicline continues to have a significant effect/benefit after a year?

A

True

22
Q

What is the mechanism of Bruproprion?

A

Its a reuptake inhibitor at the DA receptor; perhaps reducing some of the DA deficit occurring with addictions (but not entirely sure why it works)

  • Primarily an anti-depressant
23
Q

What is the mechanism of Varenicline use for nicotine addiction?

A
  • Mu-opiate receptor and DRD2 (dopamine D2 R)
  • Varenicline is like nicotine replacement therapy (NRT), but PARTIAL rather than full agonist
24
Q

What genetic variations may affect response to Nicotine addiction treatments?

A
  • Mu-opioid receptor OPRM1: Asn40Asp variant predicts response to NRT; having it means you’re more likely to respond to NRT and Varenicline
  • DRD2 141 ins/del: del C allele predicts better response to NRT (nicotine replacement therapy) than buproprion
25
Q

What is Selegeline? How is it used in the treatment of nicotine dependency?

A
  • Monoamine oxidase inhibitor
  • One of the initial anti-depressants
  • One of the components in tobacco smoke is a MAOI (A and B types); MAO-B decreases DA (need to increase it to treat nicotine dependence and to give up smoking)
  • Selegeline is used to replace this
  • Now used to treat Parkinson’s disease
26
Q

Rationale/mechanism for anti-nicotine vaccine?

A
  • Nicotine is not immunogenic; in this case bound to cholera toxin
  • Vaccine generates Abs against nicotine
  • Abs mop-up nicotine in the blood
  • Nicotine is unable to reach the brain
  • Applicable to therapy and prevention

So, Abs can reduce drug’s brain concentrations (retained in blood)

  • Animals will stop self-administrating
27
Q

T/F: Drugs of abuse easily enter the brain?

A

True

  • There are binding receptors in the brain
  • Suck out of bloodstream and drive equilibrium
28
Q

T/F: Taking drug slowly prevents abuse-enforcing behavior

A

True

29
Q

What are the different human nicotine vaccines?

A
  • Xenova product: TA-Nic
  • NABI nicotine vaccine
  • Cytos product
30
Q

Conclusions:

  • Nicotine replacement and bupropion have limited utility for sustained abstinence,
  • But pharmacogenetic matching is promising for varenicline –nicotine partial agonist
  • Selegiline may improve abstinence
  • Nicotine vaccine entering phase 3 testing with good efficacy at sufficient antibody response
  • Alcohol relapse prevention is effective using naltrexone – opiate antagonist
  • Pharmacogenetic matching based on opiate pathophysiology of disease defining an endophenotype is critical for efficacy
  • Nicotine replacement + varenicline developing pharmacogenetic matching
  • Nicotine vaccine and selegiline promising
A

(:

Term 5: Behavioral Science (24 decks)

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