Addictions Flashcards
What is the definition of tolerance?
Reduced responsiveness to a drug caused by previous administration
What types of drug are common in addictions?
Opioids
Ethanol
Barbiturates
Benzodiazepines
What is dispositional tolerance?
Less drug reaches the active site
What can be the causes for dispositional tolerance?
Less drug absorbed
Drug metabolised faster to inactive metabolites
Drug metabolised slower to active metabolites
More drug excreted
What is pharmacodynamic tolerance?
Drug has less action at the active site
What are the causes of pharmacodynamic tolerance?
Fewer drug receptors - down-regulation or internalisation
Less efficient drug receptors - less signalling down stream
What other phenomena of addiction tends to follow on from tolerance?
Withdrawal symptoms
Explain how the body develops tolerance to a drug using the example of a drug causing reduced transmitter release?
1 - Before taking the drug, the pre-synaptic terminal produces the normal amount of neurotransmitter
2 - After taking the drug, the pre-synaptic terminal produces less of the neurotransmitter
3 - Due to the reduction in neurotrasmitter production, the post-synaptic terminal increases its sensitivity by increasing the number of receptors
4 - After stopping taking the drug, the increased sensitivity produced by step 3 together with the return to normal neurotransmitter production results in withdrawal symptoms
How can the development of tolerance explain the phenomena of withdrawal from a drug?
- Due to the increased sensitivity caused by exposure to a drug, the withdrawal effects of stopping that same drug are usually the reverse of the acute effect which was desired
Give examples of addictive drugs, their acute desired effects and the associated withdrawal effects to illustrate withdrawal phenomena?
What other effect of addiction can be experienced due to development of drug tolerance?
Physical dependence - in order to avoid the (unwanted) withdrawal effects
What is the reward pathway?
- Causes a sensation of pleasure & reward
- VTA - Nucleus Accumbens - Prefontal Cortex
- When VTA neurones are stimulated dopamine is released
What does VTA mean?
Ventral Tegmental Area
Why has the reward pathway evolved?
- It encourages ‘healthy’ behaviours such as eating, drinking and sex that allow us to propogate our genes
- It is powerful
In what ways do some of the most addictive drugs influence the reward centres of the brain?
Heroin - Increases firing rate of dopaminergic neurones
Amphetamine - Increases dopamine release
Cocaine - Inhibits dopamine uptake
What mechanism of addiction forms the basis of physical dependence?
Tolerance
What mechanism of addictions forms the basis psychological cravings?
Reward centres
What aspect of addiction forms the cravings that addicts report?
Reward centres
Which gene has been implicated in addictive behaviours?
A1 Allele of the D2 Dopamine receptor gene
Give examples of stimulant drugs?
Cocaine
Amphetamines
What are the desired effects of cocaine?
- Stimulation and feeling of euphoria
- Increased alertness and energy
- Increased confidence and impaired judgement
- Reduced appetite and need for sleep
What are the negative effects of cocaine?
- Damage to nose and airways
- Convulsions with respiratory failure
- Cardiac arrythmias and MI
- Hypertension
- Paranoid psychosis
What are the withdrawal effects of cocaine?
- Depression
- Irritability
- Agitation
- Craving
- Hyperphagia
- Hypersomnia
What are various drugs within the opiates class of drugs?
- Opium
- Morphine
- Heroin (diamorphine)
- Methadone
- Codeine & dihydrocodeine
