Week 8: Psychopharmacology & addiction Flashcards
What is psychopharmacology?
The study of drug induced changes in mood, thinking and behaviour
In this case, study of the effects of drugs on the nervous system and therefore behaviour
What is a drug?
A drug is an EXOGENOUS CHEMICAL that is NOT necessary for NORMAL CELLULAR FUNCTIONING which alters the activity of certain cells in the body
What are psychoactive drugs used for?
- Altering mood
2. Treat psychopathology
What classifications of psychoactive drugs are used to alter mood?
Stimulants
Depressants
Hallucinogens
What are the drugs used to treat psychopharmacology and what are they specifically used for?
Anxiolytics: reduce anxious feelings
Antidepressant drugs: alleviate negative feeling that are associated with depression
Antipsychotic drugs: treat severe forms of psychotic behaviours (hallucinations and delusions)
What does pharmacokinetics mean?
The process by which drugs are absorbed, distributed within the body, metabolised and excreted
Drug effectiveness?
The ability of a drug to readily produce certain physiological and behavioural effects
Pharmacokinetics: What factors vary the effects of a drug?
- How/how often it is administered
- How rapidly it can enter the brain
- The context in which it is administered
- Our expectations of its effects
Drug absorption?
Refers to the mechanisms in which the drug gets into the bloodstream and is distributed throughout the body
What do drugs need to reach in order to be effective? and what do they need to do to get there?
Their site of action
- Need to access the blood system and cross the blood brain barrier
What has an influential effect on the rate at which this drug reaches its site of action
The route of administration
What have studies on differing routes of administration and cocaine shown?
Through intravenous routes of administration, blood plasma concentrations increase rapidly - within minutes we see maximal concentrations. HOWEVER, there rapidly decline and return to normal within 2 hours
For smoked, oral and intranasal administrations, we see a lower peak concentration of cocaine but the time taken to be eliminated from the blood is increased (trade off)
Explain ORAL administration?
- This is the preferred route of administration for many drugs
- Once swallowed, drugs dissolve in stomach fluids and are carried to the intestine where they are absorbed into the blood stream
- Some drugs pass through the stomach wall (alcohol) which means they take affect sooner
What are the advantages to ORAL administration of drugs?
Ease and relative safety
What are the disadvantages to ORAL administration?
There is a sense of unpredictability as it can be hard to gauge factors such as the amount and type of food in the stomach
Explain INJECTION administration
This is a common medical practice - injected drugs are strong, fast and predictable
Subcutaneously: into fatty tissue beneath skin
Intramuscularly: into large muscles
Intravenously: directly into veins
What route do those that are addicted to drugs prefer and why? Why is this a bad idea?
It is quick - straight into the bloodstream, straight to the brain.
The speed however, gives little opportunity to counteract the effects of an overdose, an impurity or allergic reactions
Explain the INHALATION route of administration
Some drugs can be absorbed into the bloodstream through the rich network of capillaries in the lungs (tobacco, marijuana)
What are some disadvantages to the INHALATION route of administration?
It is difficult to precisely regulate the dose of inhaled drugs
Substances can damage the lungs if they are inhaled chronically
What is the blood-brain barrier?
The brain has developed this barrier in order to protect itself against dangerous molecules that may damage the brain tissue
How do molecules enter pass through the BBB
Often active transport is used
Only a barrier for water molecules- those that are soluble in lipids pass through the cells that line the capillaries of the CNS
How do endothelial cells facilitate or hinder the movement of molecules across the BBB
Passive movement of water-soluble agents across the BBB is negligible because of the tight junctions between endothelial cells.
Small, lipid-soluble agents, such as antidepressants, cross the BBB via diffusion through endothelial cell
What is the best way to measure the effectiveness of a drug?
To plot a dose-response (effect) curve.
Explain dose-response curves?
You can see the effects on behaviour as the concentration of the drug is increased - reaches a point where increased concentrations no longer produce a stronger response (adverse side effect risk increases)
What is the margin of safety on dose-response curves?
A margin of safety is the difference between the dose-response curve for a drugs therapeutic effects and that for the adverse side effects
Contingent drug tolerance?
Tolerance developing to drug effects actually experienced
E.g. alcohols anti-convulsant effects- only become tolerant if given before seizures so can actually experience these effects and build up a tolerance
What is conditioned drug tolerance?
Refers to situations where tolerance effects are maximally expressed only when a drug is administered in the same situation/context in which it has previously been experienced
Drug sensitisation?
The more the animal is exposed to a drug, there is increased locomotor activity seen however this is behaviourally specific
Withdrawal effects? what about in relation to tolerance?
They are typically the opposite to the initial effects of the drug suggesting that withdrawal effects may be connected at a biological level with the changes that produced drug tolerance
Exposure to the drug produces compensatory changes in NS that offsets drugs effects and produces tolerance. When the drug is eliminated, these neural changes manifest themselves without the drug to offset them as withdrawal symptoms
What are some cocaine withdrawal symptoms?
Cravings to use, irritability, anger, lethargy, depression, insomnia
What is a palcebo?
An innocuous substance that has no specific physiological effect in its own right
Often used in experiments as ‘control’
Deals with (human) expectations of a drugs effects
What are the two classifications of drugs that affect synaptic transmission?
- Antagonist
2. Agonist
What is an antagonist?
A drug that inhibits the effects of a particular neurotransmitter
What is an agonist?
A drug that facilitates the effects of a particular neurotransmitter
What are the criteria for a substance to be considered a neurotransmitter?
Be synthesised and stored in the presynaptic neuron
Be released into the synapse when the neuron fires
Cause a post-synaptic effect after it interacts with a receptor
There must be some mechanism for degradation or reuptake
What are substances called that do not meet the requirements for being classed as a neurotransmitter?
Neuromodulators
Acetylcholine (ACh)?
Controls heart rate
Plays important role in motor movement - it is the neurotransmitter released from the motor neurons on to the muscle fibres to make them contract
Toxins (eg. black widow spider venom) can interfere with transmission and produce paralysis
What are the 5 established biogenic amine neurotransmitters?
Norepinephrine (noraderenaline) Epinephrine (adrenaline) Dopamine Histamine Serotonin
Norepinephrine?
Noradrenergic neurons (also important for regulating organs sucha s the heart) originate in the pons of the brainstem - forming an excitatory pathway known as the RAS that is primarily responsible for maintaining cortical arousal
What are deficiencies in norepinephrine linked to?
Depression and attention deficit disorders
How many pathways (originating from the brain stem) is dopamine involved in? and what are they?
2!
- Nigrostriatal pathway: begins in the substantia nigra - pathway for voluntary movement (deficiencies = parkinsons)
- mesocortical system or reward system
What else is serotonin known as?
5-hydroxytryptamine (5-HT)
What is serotonin involved in?
The sleep/wake cycle, mood, impulsive behaviour, and appetite
What behavioural disorders is serotonin implicated in?
Sleep disorders, aggression, obesity, anorexia and depression
However treatment is never as simple as just increasing the levels of these neurotransmitters
What are the brand names of SSRI’s?
Zoloft
Prozac
Luvox
Paxil
Explain what ionotropic means?
Direct activation brings about immediate response
Neurotransmitter binds to the receptor and the channel opens neurotransmitter is released into the synaptic cleft
Explain what metabotropic means?
Indirect activation involves a prolonged response amplified over time
Neurotransmitter binds to receptor
G protein activated and binds to ATP
Second messenger molecules produced activating enzymes that open the channel
Second messenger are signalling molecules that are released by the cell in response to exposure to extra cellular signalling molecules which are the first messengers
Natural rewards and dopamine?
Natural rewards such as food and sex increase dopamine in the brain
What are the reinforcing effects of cocaine and amphetamine mediated by?
Largely mediated by the dopamine system
Disruption, destruction and lesions block reinforcing effects of related locomotor activity
THC and dopamine?
The acute reinforcing effects of THC also involve activation of the dopamine system mediated by cannabinoid and opioid receptors
What is cross tolerance?
One drug can produce tolerance to another drug that act by the same mechanism
What is metabolic tolerance?
It results from changes that reduce the amount of the drug getting to its sites of action
What is functional tolerance?
Results from changes that reduce the reactivity of the sites of action to the drug
Psychedelic-assisted psychotherapy?
Therapeutic practices that involve the ingestion of psychedelic drugs
When ingested in a controlled and setting can induce an experience that is safe and provides benefits
What external factors can ‘make the brain go wrong’?
Malnutrition Parental abuse Toxins (alcohol) Infections (meningitis) Trauma (head injury)
What internal factors can ‘make the brain go wrong’?
Developmental problems (autism) Acquired abnormalities (epilepsy) Age-related damage (dementia)
What do psychedelics do?
Take away limitations and increases brain flexibility
Inhibits the ‘default mode network’ which regulates executive brain function
