6/19- Alcohol/Substance Abuse 4: Flashcards Preview

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

Flashcards in 6/19- Alcohol/Substance Abuse 4: Deck (30):
1

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

Opioid antagonists

2

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

- Varenicline

- Selegiline

- Nicotine vaccine

3

What is the priming effect?

Think: Lay's potato chips

- Once you start, it's hard to stop; start craving more rather than satisfying the craving

4

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

- Craving reduction

- Modifying experience of intoxication

- Inhibition of the priming effect of the initial drink

5

What is the process in which alcohol stimulates ___ receptors?

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...

6

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

- Naltrexone raises beta endorphin

- Alcohol can not raise BE

- Relapse prevented

7

Which patients are more responsive to Naltrexone?

- 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

8

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

- 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

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

Get a significant raise for relatively small amount of alcohol 

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10

Comparison between family history positive and negative people on Naltrexone?

- 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

What are pharmacogenetics?

Effects of genetic polymorphisms on pharmacological effects of drugs or medications

- Matching patients to treatments based on genetics

- Personalized medicine

12

Mice without u opiate receptors will not do what?

Self-administer alcohol

13

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

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

What gene was found to predict Naltrexone response in alcoholics?

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

What is an endophenotype?

Endorphin dependent alcoholism

- Alcohol -> increase in endogenous opioids

- Euphoria/stimulation

- Sensitive mu receptors

- Family history

- Alcohol craving

16

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

- Nicotine replacement therapies

- Buproprion

17

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

- Both Buproprion and Nicotine patch seem to help the most

- However, at a year, they're all about the same (20%) 

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18

Approved medications for treating nicotine addiction?

- Nicotine patch, gum, lozenge, inhaler, spray

- Buproprion (anti-depressant)

- Varenicline (Chantix): partial nicotinic receptor agonist (a4B2 receptor)

(Nicotine vaccine promising; on the way)

19

Most new drugs are what class? Mechanism?

Partial agonists

- Agonists at low doses

- Antagonists at high doses

20

Nicotine stimulates what pathway?

Varenicline stimulates what?

- 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

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

True

22

What is the mechanism of Bruproprion?

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

What is the mechanism of Varenicline use for nicotine addiction?

- Mu-opiate receptor and DRD2 (dopamine D2 R)

- Varenicline is like nicotine replacement therapy (NRT), but PARTIAL rather than full agonist

24

What genetic variations may affect response to Nicotine addiction treatments?

- 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

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

- 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 

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26

Rationale/mechanism for anti-nicotine vaccine?

- 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

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

True

- There are binding receptors in the brain

- Suck out of bloodstream and drive equilibrium

28

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

True

29

What are the different human nicotine vaccines?

- Xenova product: TA-Nic

- NABI nicotine vaccine

- Cytos product

30

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

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