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Neuropharmacology > Lecture 14 > Flashcards

Lecture 14 Flashcards

1
Q

Definition of substance abuse

A

Harmful/hazardous use of psychoactive substances e.g. alcohol and illicit drugs

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2
Q

Definition of drug dependence

A

Body’s physical need/addiction to a specific agent

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3
Q

Why are certain drugs addictive?

A
  • act in reward pathways to produce euphoria - adaptation of CNS circuits and withdrawal symptoms occur when activation stops - tolerance occurs so increased doses are required
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4
Q

What are the brain areas associated with the reward pathway?

A
  • frontal cortex - nucleus accumbens - VTA - striatum - substantia nigra - hippocampus - raphe nucleus
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5
Q

What are the neurotransmitters associated with the reward pathways?

A
  • dopamine - serotonin
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6
Q

Why are there reward pathways?

A

To reward us for signals that promote survival e.g. food consumption, drinking water, procreation child nutrition

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7
Q

What is the common pathway of addiction?

A
  • dopamine released into nucleus accumbens - control of dopamine release by GABA neurones= inhibited by opiates - VTA and nucleus accumbens mostly targeted
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8
Q

How do drugs over-ride in-built controls?

A
  • drugs over-ride top-down control (control and self-regulation) - salience= motivational component to a rewarding stimulus (a drug)
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9
Q

What areas do drugs over-ride?

A
  • amygdala and hippocampus (memories of pleasurable events) - orbitofrontal cortex (fuels drive) - prefrontal cortex and cingulate gyrus (weakened control)
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10
Q

What is the physical dependence of addiction?

A
  • resetting homeostatic mechanisms in response to repeated drug use - withdrawal syndrome (sign of physical dependence) - withdrawal arises due to abrupt termination of drug use
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11
Q

What is the psychological dependence of addiction?

A
  • motivational component, craving for the drug - not always associated with physical dependence - persists longer than physical dependence
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12
Q

What is innate tolerance?

A

Genetically determined sensitivity i.e. occurs after first dose

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13
Q

What is acquired tolerance?

A
  • pharmacokinetic= changes in metabolism and absorption reduce systemic blood concentration - pharmacodynamic= adaptive changes within the system resulting in altered response to the drug i.e. receptor desensitisation
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14
Q

What is cross tolerance?

A

Resistance to the effects of a substance because of exposure to a pharmacologically similar substance e.g. cocaine and amphetamines

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15
Q

Describe pharmacodynamic tolerance

A
  • GPCR activation occurs - phosphorylation of receptors occurs - arrestin binding= prevent receptor signalling - endocytosis of receptors
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16
Q

Would you expect a larger or smaller number of GPCRs in long-term addicts?

A

Smaller number of GPCRs because of endocytosis

17
Q

How does tolerance occur in cocaine addicts?

A
  • prevents dopamine and 5-HT uptake - cycle between euphoria and dysphoria (can lead to paranoia and psychosis) - chronic use= speed to dysphoria increases - memory increases drive to increase euphoric state
18
Q

How does cocaine modulate reward pathways?

A

Blocks uptake transporters for dopamine and 5-HT= increases levels of extracellular dopamine and 5-HT

19
Q

How does cocaine modulate synaptic properties?

A
  • changes in AMPA receptor levels= related to glutamatergic transmission - impaired cytosine-glutamate exchange - changes in intrinsic membrane excitability of medium-spiny neurones
20
Q

How does cocaine affect the morphology of medium-spiny neurones?

A
  • increases spine numbers - increases synapse synapse numbers within nucleus accumbens
21
Q

How do we measure study brain circuit changes using animal models?

A
  • choice as a method of measuring drug addiction - sweet vs drug solution - food, ethanol and intracranial self-administration - forced swim test
22
Q

What are the principles for the effective treatment of drug dependence?

A
  • quick and easy access to treatment - addresses all of the patients’ needs, not just drug use - patient must stay long enough in treatment - requirement for counselling and other behavioural therapies - medication in combination with behavioural therapies - drug use during treatment must be monitored - test for HIV/AIDS
23
Q

What are the pharmacological approaches to treating drug dependence?

A
  • alleviate with withdrawal symptoms e.g. methadone, nicotine patches - long term drug substitution - block drug response e.g. naltrexone - aversive therapies e.g. disulfiram - treat underlying mental health problems e.g. antidepressants
24
Q

Disulfiram (antabuse) as an aversive therapy

A
  • small amounts of alcohol can precipitate a reaction - nausea, vomiting, sweating - confusion - hypotension - blurred vision
25
Q

What are the stages of cocaine withdrawal?

A
  • crash= hunger, anxiety, fatigue, extreme depression - withdrawal= dysphoria, anxiety, depression, paranoia - extinction= low mood, episodic cravings
26
Q

What are the methods of treating cocaine addiction?

A
  • no specific pharmacological interventions - contingency management= reward-based system on the basis of free urine tests - CBT= recognise situations in which they are likely to relapse
27
Q

What are the stages of opioid intoxication?

A
  • rush= pleasure, facial flushing, resistance to tolerance - nod= sleepiness, virtual unconsciousness, detached - high= feeling of well-being (shows tolerance) - being straight= no high but no withdrawal
28
Q

What are the mechanisms of opioid action?

A
  • activate opioid receptors on GABA neurons in VTA - increased dopamine release into nucleus accumbens - reduced cAMP= when opioid are stopped cAMP rebounds leading to hyperactivity
29
Q

What are the treatments of opioid addiction and how do they work?

A
  • methadone, buprenorphine or legal heroin - alleviate withdrawal symptoms - long-term susbtution
30
Q

Why are addicts at risk of overdose if they miss their methadone prescription?

A

Loss of tolerance

31
Q

Why is buprenorphine used?

A
  • precipitates opiate withdrawal - aimed to deter misuse - ineffective if taken orally but if crushed, dissolved or injected= naloxone blocks buprenorphine
32
Q

Why would you use naltrexone?

A
  • opioid receptor antagonist - in case of accidental overdose - BUT poor adherence limits effectiveness
33
Q

Where does nicotine act in the brain?

A
  • hippocampus - VTA - amygdala - nucleus accumbens - prefrontal cortex
34
Q

What are the symptoms of nicotine withdrawal?

A
  • headache - nausea - constipation or diarrhoea - anxiety - depression - insomnia
35
Q

What are the methods to treat nicotine addiction?

A
  • nicotine replacement e.g. gum - transdermal patches - e-cigarettes - varenicline= partial nicotine agonist - bupropion= nicotine antagonist
36
Q

What are the pharmacological treatments for alcohol addiction?

A
  • acamprosate calcium SR tablets - disulfiram - alleviate withdrawal symptoms= benzodiazepines, clonidine - opioid receptor antagonists= reduces endorphin effects in reward properties
37
Q

How are acomprosate calcium SR tablets used to treat alcohol addiction?

A
  • weak NMDAR antagonist reduces craving - used with counselling after abstinence

Neuropharmacology (15 decks)

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