Lecture 34 Flashcards
What are psychoactive drugs?
Drugs which affect the way people think, feel and behave
What is abuse liability?
A measure of the likelihood that use of a drug will result in drug addiction
What are the criteria used to assess a drug as having abuse potential?
Having pharmacological equivalence to other known drugs of abuse
Demonstrate a reinforcing effect
Tolerance and dependence
What is the most key factor in the abuse potential of a drug?
If it is intrinsically rewarding
What is the dopamine pathway?
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
What are the functions of the dopamine pathway?
Reward, pleasure, euphoria, motor function, compulsion, preservation
What are the functions of the serotonin pathways?
Mood, Memory processing, sleep, cognition
What is the evidence for dopaminergic involvement in brain reward?
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
What demonstrates the reinforcing effects of abuse liability?
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
What are the consequences of repeated administration of drugs of abuse?
If the drug has the ability to induce neuroadaptive changes then following chronic administration tolerance and physical dependence may follow
What is dependence with regards to drugs of abuse?
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
What are the central nervous system depressents?
Opiods such as morephine, heroin, codeine and methadone
Sedative-hypnotics such as alcohol, benzodiazepines (diazepam, temazepam), barbiturates (phentobarbitone, pentobarbitone), Gamma Hydroxybutyrate
What are the psychomotor stimulants?
Nicotene
Amphetamines ( Methanphetamine, methylphenidate, Ritalin, MDMA)
Cocaine
Methylxanthines (caffeine)
What are the psychomimetics/hallucinogens?
LSD group (LSD, mescaline,, psilocybin)
Dissociative anaesthetics (PCP, angel dust)
Cannabis
Solvents and aerosols such as toluene, nitrous oxide, amyl nitrate, butyl nitrate
What are the pharmacodynamics of alcohol?
Alcohol has low potency and a large dose is required to gain the desired effect resultin in toxic side effects being more common
What are the biphasic effects of alcohol?
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
What are the acute toxic effects of alcohol?
Respiratory depression Hypothermia Impairment of memory and learning Psychomotor impairment/relaxation Nausea and vomiting
What can occur in an overdose of alcohol?
Potentially fatal due to respiratory depression and choking
What are the long term effects of toxic alcohol exposure?
Dependence, Liver disease, gastrointestinal disease, anaemia, CNS disturbance, depression
What is the mechanism of action of alcohol?
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
What are the pharmacokinetics of alcohol absorption?
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
What are the pharmacokinetics of alcohol distribution?
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
What are the pharmacokinetics of alcohol metabolism?
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)
What are the effects of variants of alcohol dehydrogenase enzyme?
Some variants cause a slower build up of acetaldehyde causing reduced flushing
What are the effects of aldehyde dehydrogenase enzyme variants?
More acetaldehyde accumulates
Nasty side effects as toxic
Aversive behaviour allowing it to be protective
Found in some Asian populations
What is Disulfiram (anatbuse)?
An aversive agent in people with alcohol dependence
It inhibits acetaldehyde dehydrogenase so even a small amount of alcohol will cause acetaldehyde syndrome
What is acetaldehyde syndrome?
Throbbing headache, nausea, vomiting, chest pain
What is alcohol withdrawal?
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
