Lecture 34 Flashcards

1
Q

What are psychoactive drugs?

A

Drugs which affect the way people think, feel and behave

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2
Q

What is abuse liability?

A

A measure of the likelihood that use of a drug will result in drug addiction

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3
Q

What are the criteria used to assess a drug as having abuse potential?

A

Having pharmacological equivalence to other known drugs of abuse
Demonstrate a reinforcing effect
Tolerance and dependence

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4
Q

What is the most key factor in the abuse potential of a drug?

A

If it is intrinsically rewarding

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5
Q

What is the dopamine pathway?

A

Ventral Tegmental area is a part of the midbrain which consists of dopamine, GABA and glutamate neurons
This signals the Nucleus Accumbens which is found in the striatum (basal ganglia) receives input from neurons of VTA, hippopcampus, amygdala and prefrontal cortex Release of dopamine here drives the mesolimbic system
The amygdala which is located in the temporal lobe and associated with the assignment of emotions particularly fear and anxiety
Hippocampus and this is also in the temporal lobe and responsible for memory

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6
Q

What are the functions of the dopamine pathway?

A

Reward, pleasure, euphoria, motor function, compulsion, preservation

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7
Q

What are the functions of the serotonin pathways?

A

Mood, Memory processing, sleep, cognition

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8
Q

What is the evidence for dopaminergic involvement in brain reward?

A

Released in Nucleus Accumbens following natural rewards or electrical stimulation
Antagonists of dopamine block self-stimulation
Dopamine agonists will be injected into the nucleus accumbens through self administration

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9
Q

What demonstrates the reinforcing effects of abuse liability?

A

Self administration is considered the primary criterion by which a drug can have significant abuse potential as administration of the drug can occur to the point where it is obsessive and detrimental to health
It can be shown by using animals trained in drug discrimination, able to recognize a drug that is reinforcing from a pacebo can also distinguish between that drug and other non-reinforcing drugs

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10
Q

What are the consequences of repeated administration of drugs of abuse?

A

If the drug has the ability to induce neuroadaptive changes then following chronic administration tolerance and physical dependence may follow

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11
Q

What is dependence with regards to drugs of abuse?

A

With prolonged exposure to a drug the neurones adapt to the presence of the drug
Removal of the drug or reduction in use will result in withdrawal syndrome reflecting the CNS hyper-arousal
These symptoms are commonly the opposite to the acute effects of the drug
This is a key factor in motivating individuals to continue using

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12
Q

What are the central nervous system depressents?

A

Opiods such as morephine, heroin, codeine and methadone
Sedative-hypnotics such as alcohol, benzodiazepines (diazepam, temazepam), barbiturates (phentobarbitone, pentobarbitone), Gamma Hydroxybutyrate

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13
Q

What are the psychomotor stimulants?

A

Nicotene
Amphetamines ( Methanphetamine, methylphenidate, Ritalin, MDMA)
Cocaine
Methylxanthines (caffeine)

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14
Q

What are the psychomimetics/hallucinogens?

A

LSD group (LSD, mescaline,, psilocybin)
Dissociative anaesthetics (PCP, angel dust)
Cannabis
Solvents and aerosols such as toluene, nitrous oxide, amyl nitrate, butyl nitrate

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15
Q

What are the pharmacodynamics of alcohol?

A

Alcohol has low potency and a large dose is required to gain the desired effect resultin in toxic side effects being more common

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16
Q

What are the biphasic effects of alcohol?

A

In low doses there is mild euphoria and a stimulation of behaviour
In higher doses there is impairment which is noticeable with greater blood alcohol concentrations

17
Q

What are the acute toxic effects of alcohol?

A
Respiratory depression
Hypothermia
Impairment of memory and learning
Psychomotor impairment/relaxation
Nausea and vomiting
18
Q

What can occur in an overdose of alcohol?

A

Potentially fatal due to respiratory depression and choking

19
Q

What are the long term effects of toxic alcohol exposure?

A

Dependence, Liver disease, gastrointestinal disease, anaemia, CNS disturbance, depression

20
Q

What is the mechanism of action of alcohol?

A

Binds to a subunit of the GABAa receptor and enhances release of the inhibitory transmitter GABA to cause general CNS depression effects
Decreases activity at glutamate receptors preventing calcium ions from entering cell which normally activates the cell

21
Q

What are the pharmacokinetics of alcohol absorption?

A

It is water soluble and is absorbed through passive diffusion in the GI tract via hepatic circulation (80%) and the stomach (20%)
Reaches the brain within 5 minutes of indigestion
Peak blood concentration within 30-90 minutes
Absorption rate typically varies with beverage type and presence of food

22
Q

What are the pharmacokinetics of alcohol distribution?

A

Rapidly distributed throughout body water accumulating in tissues with high water content
Readily crosses both blood brain and placental barriers
In general females have smaller proportions of body water than males and body water declines with age As a result females and elderly will have higher blood alcohol concentrations than younger people

23
Q

What are the pharmacokinetics of alcohol metabolism?

A

90% of alcohol is metabolised
At the first metabolic step it is metabolized into acetaldehyde via alcohol dehydrogenase (rate limiting step with the enzymes quickly becoming saturated at low levels of alcohol)
The second metabolic step is acetaldehyde being rapidly metabolized by the enzyme aldehyde dehydrogenase in to acetate (this is usually a rapid reaction as acetaldehyde is toxic)

24
Q

What are the effects of variants of alcohol dehydrogenase enzyme?

A

Some variants cause a slower build up of acetaldehyde causing reduced flushing

25
Q

What are the effects of aldehyde dehydrogenase enzyme variants?

A

More acetaldehyde accumulates
Nasty side effects as toxic
Aversive behaviour allowing it to be protective
Found in some Asian populations

26
Q

What is Disulfiram (anatbuse)?

A

An aversive agent in people with alcohol dependence

It inhibits acetaldehyde dehydrogenase so even a small amount of alcohol will cause acetaldehyde syndrome

27
Q

What is acetaldehyde syndrome?

A

Throbbing headache, nausea, vomiting, chest pain

28
Q

What is alcohol withdrawal?

A

Dependence of alcohol can occur following repeated administration
This manifests as increasing tolerance requiring more drug to get to the same effect
If alcohol is dramatically reduced then withdrawal of CNS hypersensitivity may occur