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Exam 2 APP > APP Module (GTown) - Addiction, Alcoholism, and Drugs of Abuse (Hrs 1 and 2) > Flashcards

APP Module (GTown) - Addiction, Alcoholism, and Drugs of Abuse (Hrs 1 and 2) Flashcards

1
Q

All drugs of abuse interfere in some way with what?

A

ventral striatum

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2
Q

What is tolerance?

A

Decreased response to a repeated dose of substance over time; or the need to increase a dose to obtain a similar effect

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3
Q

What are some withdrawal symptoms of alcohol?

A
  • tremor
  • seizure
  • DTs
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4
Q

What are the three factors which influence addiction?

A
  • drug
  • user (genetics)
  • environment
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5
Q

Per statistics, which substance seems to be the “most” addictive?

A

nicotine

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6
Q

What is the typical human use pattern?

A

1) initial experimentation or use
2) repeated use
3) compulsive drug-seeking
4) abstinence

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7
Q

What properties does alcohol have?

A

anxiolytic, hypnotic, and anesthetic properties

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8
Q

How do you make beer?

A

1) Harvest some hops and barley.
2) Get some brewer’s yeast.
3) Get a container with some water and add the yeast with the barley and hops and then wait.

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9
Q

What is the affinity of ethanol for interactions?

A

millimolar range

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10
Q

What is the affinity of dopamine for its receptor?

A

nanomolar range

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11
Q

What do the differing affinities of dopamine and ethanol mean?

A

Lower affinities mean you mean much less of the substance to produce a response

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12
Q

What might be considered an intoxicating dose of ethanol?

A

Those above ~15mM (A moderately intoxicating blood alcohol level of 0.08% (80 mg/dl) is equivalent to an ethanol concentration of 17 mM.)

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13
Q

What are some molecular characteristics of ethanol?

A

amphipathicity and ability to readily cross lipid membranes

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14
Q

What are the main CNS effects of alcohol?

A
  • inhibition of excitatory neurotransmission and enhancement of inhibitory neurotransmission
  • DA release modulation
  • disinhibition, ataxia, and sedation
  • chronic use leads to tolerance, dependence, etc.
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15
Q

How does alcohol mediate its effect on plasma membranes?

A

Alcohol intercalates itself between lipid molecules in the plasma bilayer and affects both the membrane fluidity as well as protein function

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16
Q

What are the main brain regions affected by alcohol?

A
  • mesolimbic DA system
  • amygdala
  • striatum
  • hippocampus
  • cortex/cerebellum
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17
Q

What changes do you see in the brain of a chronic alcohol user?

A

↓ brain mass
↑ ventricle size
larger gaps between gyri and sulci

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18
Q

What effect does alcohol have on the firing at a NMDA synapse?

A

Markedly attenuates the inward current usually seen with glutamate dosing

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19
Q

What are the main channels which alcohol affects?

A

1) NMDA and kainate
2) GABA-A
3) nACh
4) 5-HT3

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20
Q

What are the features of an NMDA receptor?

A

1) tetramer
2) binds glutamater and glycine as a co-agonist
3) voltage-dependent Mg2+ block
4) NR1 and NR2 subunits

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21
Q

What type of receptors does alcohol seem to affect?

A

“cys-loop” family which includes nAChRs, 5-HT3, GABA-A

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22
Q

How does alcohol affect GABA-A receptors?

A

potentiates flux of potassium ions

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23
Q

Where are 5-HT3 receptors primarily expressed?

A

emetic centers of the brain

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24
Q

What is Zofran?

A

Ondansetron is an anti-emetic which antagonizes 5-HT3 receptors

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25
Q

Why is Zofran being used for alcohol abuse?

A

Seems to reduce cravings in early-onset alcoholics

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26
Q

What are the six major receptor effects that alcohol has?

A

1) decrease in NMDAR activity
2) decrease in kainate receptor activity
3) decrease in voltage-sensitive calcium channels
4) increase in GABA-A activity
5) increase in 5-HT3 activity
6) increase in nAChR activity

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27
Q

What do you see in fMRI images of intoxicated patients while performing a task?

A

Global depression of brain activity

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28
Q

What are the four current pharmacological treatments for alcohol dependence?

A

1) disulfiram
2) naltrexone
3) acamprosate
4) long-acting naltrexone

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29
Q

What is disulfiram and how does it work?

A

Disulfiram blocks the action of acetaldehyde dehydrogenase leading to an accumulation of acetaldehyde in the body which has a lot of unpleasant effects

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30
Q

What is the treatment for acute methanol poisoning and how does it work?

A

Ethanol. Using ethanol actively competes for the alcohol dehydrogenase enzyme which in turn produces acetaldehyde instead of the far more toxic formaldehyde from methanol

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31
Q

What is naltrexone and how does it work to treat alcohol abuse?

A

Naltrexone is an opioid receptor antagonist which decreases DA release associated with alcohol expectancy and consumption

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32
Q

What is acamprosate and how does it work to treat alcohol abuse?

A

Acamprosate has complex effects on the glutamate-NMDA system and is also a GABA agonist. It seems to increase abstinence rates by working in opposition to the effects of alcohol

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33
Q

What are some examples of Schedule I drugs?

A
  • heroin
  • LSD
  • marijuana
  • MDMA
  • THG (an anabolic steroid)
34
Q

What are three requirements for a schedule I drug?

A

1) high potential for abuse
2) no currently accepted medical use
3) a lack of accepted safety for its use under medical supervision

35
Q

Can you prescribe Schedule I drugs as a physician?

A

Nope

36
Q

Who determines whether drugs are controlled and in which schedule they are put?

A

DEA, FDA, and congress

37
Q

What is the difference between desensitization and tolerance?

A

Sensitization is the increase in response to a repeated administration of drug. Tolerance is the decrease in a response to a repeated administration of a drug.

38
Q

What are some pharmacological effects of nicotine?

A
  • facilitates memory
  • anxiolytic
  • anti-nociceptive properties
  • improves attention
  • both stimulant and relaxant
39
Q

What is the affinity of nicotine for the nicotinic receptor?

A

nanomolar range

40
Q

What are the two main subtypes of nicotinic receptor in the brain?

A

α7 homomeric receptor

α4β2 homomeric receptor

41
Q

What type of receptor is a nAChR?

A

pentameric ionotropic receptor

42
Q

What is the ion channel that the α4β2 receptor is associated with?

A

non-selective cation channel permeable to sodium and calcium

43
Q

Where are the nAChRs found in the brain?

A

dopaminergic neurons which reinforces the rewarding effect of nicotine

44
Q

What is activation of the nicotinic receptor characterized by in the presence of nicotine

A

rapid desensitization

45
Q

Why is cytisine not addictive like nicotine?

A
  • no effect on increased receptor expression

- no desensitization at the receptor

46
Q

What is found regarding nicotinic receptors in post-mortem brain tissue

A

In chronic smokers, the nicotinic receptor has been upregulated

47
Q

What is special about the upregulation of receptors which nicotine causes?

A

It is not dependent on mRNA transcription which means nicotine is actively stabilizing and facilitating receptor expression directly

48
Q

What factors decrease nicotinic receptor expression in the brain?

A
  • aging

- dementia and Alzheimer’s

49
Q

How does varenicline work?

A

full agonist at the α7 receptor. partial agonist at the α4β2 receptor

50
Q

What are examples of some other pharmacological therapies for nicotine addiction?

A
  • bupropion

- rimonabant (CB1R antagonist)

51
Q

How does the CB1R antagonist rimonabant exert its effect?

A

It’s thought that chronic nicotine use leads to increased expression of CB1Rs in the mesolimbic system and antagonizing this lessens nicotine’s rewarding effects

52
Q

What does alcohol do in conjunction with nicotine?

A

Alcohol potentiates the DA release of nicotine when used together

53
Q

How does cocaine work?

A

Inhibits DAT leading to increased concentrations of dopamine in the synapse for longer times

54
Q

What is a pharmacological effect seen with cocaine administration?

A

Sensitization. Increased response to repeated doses of cocaine and even generalization to associated and similar stimuli

55
Q

What effect does cocaine have on the neurons in the NAc?

A

Increased AMPA receptor expression. Change in shape and size of dendritic spines

56
Q

Who self-administers more cocaine on a daily basis if given the chance? Adolescents or adults

A

Adolescents!

57
Q

How does cocaine exert its local anesthetic effect?

A

inhibition of sodium channels

58
Q

What are the four receptor subtypes of opioid receptor?

A

mu, delta, kappa, and nociceptin

59
Q

What is the delta receptor in the brain involved with?

A
  • pain relief
  • antidepressant effects
  • physical dependence
60
Q

What is the kappa receptor in the brain and spinal cord associated with?

A
  • sedation
  • spinal analgesia
  • pupil constriction
61
Q

What is the mu receptor in the brain and spinal cord associated with?

A
  • physical dependence
  • respiratory depression
  • euphoria
  • pupil constriction
  • supraspinal analgesia
62
Q

What is the nociceptin receptor in the brain and spinal cord associated with?

A
  • appetite
  • depression and anxiety
  • development of tolerance to mu agonists
63
Q

What are some effects of the opiate system?

A

pain relief
euphoria
strong tolerance and withdrawal effects

64
Q

What is a mu agonist?

A

morphine

65
Q

What separates heroin from methadone?

A

Heroin has larger peaks and valleys during administration while methadone is longer-lasting leading to a more level concentration in the body

66
Q

What are some endogenous opiates?

A
  • endorphins
  • dynorphin
  • enkephalins
67
Q

What types of molecules are the endogenous opiates?

A

neuropeptides

68
Q

How do the opioid receptors signal?

A

As GPCRs through the Gi signaling pathway

69
Q

What are the CNS endorphin pathways like?

A

similar to brain reward pathways

70
Q

What are some maintenance medications for opiate abuse?

A
  • naltrexone

- methadone

71
Q

What is the active component of cannabis?

A

THC

72
Q

How many cannabinoid receptor types are there?

A

Two: CB1 and CB2

73
Q

What are some endogenous cannabinoids?

A

2-AG and anandamide

74
Q

Where is the CB1 receptor located?

A

Pretty much through the body and CNS/PNS

75
Q

Where is the CB2 receptor located?

A

immune system

76
Q

What type of receptors are the CB1 receptors?

A

GPCRs which signal through Gi and inactivate pre-synaptic calcium release

77
Q

What is the effect of CB1 receptor agonists?

A

Inhibition of motor performance

78
Q

Why do CB1R agonists affect motor movement?

A

Because they are highly expressed in the GP and striatum

79
Q

What is unique about the CB1 receptor?

A

It engages in retrograde signaling

80
Q

What is the effect of CB1 receptors in the hypothalamus linked to?

A

appetite regulation

Exam 2 APP (5 decks)

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