Genetics, Routes of Administration Flashcards
What do twin studies show about addiction?
Monozygotic twins have more similar rates of addiction than heterozygotic twins
What do adoption studies show about addiction?
More likely to display birth family than adopted family habits
How do clinical studies need to be conducted?
Double-blind
Randomized
Controlled
What is the reward deficiency hypothesis?
Self-medicating a chronic deficiency in subjective hedonic tone that is genetic or acquired by using addictive drugs
What are 3 things that may explain the reward deficiency hypothesis?
- A deficiency of D2 receptors in the reward circuit
- An aberration (abnormality) in D3 receptors in the reward circuit
- Due to a deficiency in presynaptic DA levels in the NAc
What do addictable mice display?
A pathological atrophy of the neuro filamentary transport system for the DA-synthesizing enzyme tyrosine hydroxylase in DA-ergic VTA neurons
How do males with robust levels of striatal DA experience methylphenidate?
They don’t like it
How do males with deficits in striatal D2 levels experience methylphenidate?
They experience pleasure
What are characteristics that predict a higher vulnerability to drug-seeking behaviour in animals?
High reactivity to stress
High novelty-induced locomotor activity
High novelty-seeking
High trait impulsivity
What are personal attributes that predict a higher vulnerability to addiction in humans?
Sensation and novelty-seeking
Trait impulsivity
Anti-social conduct disorder
What do most addicts in rehab report?
Traumatic experiences in their past or a mood-related condition
What are striatal D2 levels like in dominant and submissive monkeys?
Dominant = high levels
Submissive = low levels, lower D2 receptors, higher vulnerability to cocaine self-administration
How are rats predisposed to self-administration?
Reduced D2/D3 receptor expression in NAc, leads to greater impulsivity
What does high reactivity predict?
A tendency to self-administer addictive drugs
What is the biopsychosocial model of addiction?
Ties together several aspects of biology, psychology, and social interaction
-drug exposure (naivety)
-DA functionality
-behavioural traits
What is polygenicity?
Multiple genes involved in addiction
What are predispositions?
A tendency/vulnerability to suffer from a particular condition
What is the link between a gene and addiction?
Genes + proteins influence pharmacodynamics which influences physiology which influences behaviours
What are SNPs?
Base pair differences within coding and non-coding regions between alleles of genes in the population
What is GWAS?
Gene set association, heritability enrichment analysis
What is neuronal adhesion?
Important for plasticity
What are the traits of faster absorption routes?
Faster delivery to the brain
Higher peak
Stronger high
Drug doesn’t stay in brain long
What are the traits of slower absorption routes?
Peak not as high
High not as intense
Prolonged duration in the brain
What is bioavailability?
Amount of administered drug reaching systemic circulation
What is the drug onset of inhalation?
7-10 seconds
What is the duration of an inhalation high?
2-4 hours
What is the bioavailability of inhalation?
5-99%
What is the shortest circulatory path to the brain?
Inhalation
What is the drug onset of injection?
10-20 seconds
What is the duration of an injection high?
2-4 hours
What is the bioavailability of injection?
100%
What is the second shortest circulatory path to the brain?
injection
no first-pass metabolism
What can happen after repeated injection?
Veins collapse
What is the drug onset of insufflation?
10-45 minutes
What is the duration of an insufflation high?
5-8 hours
What is the bioavailability of insufflation?
Up to 80%
Does insufflation have first-pass metabolism?
No
What is the drug onset of ingestion?
20-45 minute onset
What is the duration of the high of ingestion?
6+ hours
What is the bioavailability of ingestion?
5-99%
Does ingestion involve first-pass metabolism?
Yes
Stomach pH can alter the chemistry
What routes have a greater abuse potential?
Ones that have a quicker onset
What do dose-response curves describe?
Relationships between [drug] and effects
What axis will tell you which drug is most effective?
The Y axis
What axis will tell you which drug is most potent?
The X axis
What is the therapeutic index?
LD50/ED50
What is synergy?
Drugs working together to have a greater effect
What is antagonism?
Drugs interact to decrease the effect
What is the half-life of drugs?
The time to remove 50% of [drug] from circulation
