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Pmcol 305 > Genetics; Routes of Administration > Flashcards

Genetics; Routes of Administration Flashcards

1
Q

twin studies

A

monozygotic twins have more similar rates of addiction than heterozygotic twins

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2
Q

adoption studies

A

more likely to display birth family than adopted family habits
genetic predispositions

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3
Q

randomized control trial

A

double-blind, randomized, and controlled clinical studies
more informed

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4
Q

reward deficiency hypothesis

A

nature then nurtured
self-medicating a chronic deficiency in subjective hedonic tone that is genetic by using additive drugs

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5
Q

neurobiological causes of reward deficiency hypothesis

A
  1. deficiency of D2 receptors in the reward circuit = less effective signaling
  2. an aberration (impaired functioning) in D3 receptors in the reward circuit
  3. deficiency in presynaptic dopamine levels in the nucleus accumbens = terminals don’t release enough; affect pathway
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6
Q

mice preferences for addictive drugs

A

bred mice sort themselves into high or low seeking behavioural categories by repeated exposure to addictive drugs - Lewis vs Fischer rats

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7
Q

addictable mice

A

display a pathological atrophy of the neurofillamentary transport system for the dopamine synthesizing enzyme tyrosine hydroxylase in dopaminergic VTA neurons
= deficiency in dopamine synthesis

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8
Q

deficiency in dopamine synthesis in addictable mice

A

concomitant aberrations in post-receptor signal transduction mechanisms compared to drug-avoidant animals
molecular event contributes to psychological effect

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9
Q

striatal dopamine D2 receptor expression level - Ritalin

A

predicts subjective experience with methylphenidate
healthy male subjects with naturally high dopamine synthesis report dipleasurable experience with Ritalin
subjects with deficits in striatal D2 levels report a pleasurable experience
PET scan

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10
Q

PET scan

A

measuring radioactivity - measure activity in the brain
label D2 receptors - show striatal D2 receptor level expression

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11
Q

animal attributes predict vulnerability to addiction

A

high:
reactivity to stress
novelty induced locomotor activity
novelty-seeking
trait impulsivity

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12
Q

epigenetics

A

chemical modifications that determine gene transcription are inherited

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13
Q

human attributes predict vulnerability to addiction

A

sensation- and novelty-seeking
trait impulsivity
anti-social conduct disorder

past traumatic experiences or mood-related conditions

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14
Q

Striatal D2 levels in monkeys

A

high levels in socially dominant monkeys
low levels in submissive monkeys
differences amplified in socially-housed monkeys

submissive - lower D2 receptor levels and higher vulnerability to cocaine self-administration

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15
Q

impulsivity and dopamine biology pre-dispose self-administration in rats

A

reduced D2/D3 receptor expression in NAc of drug-naive high-impulsive rats
high impulsive rats display greater cocaine self-administration

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16
Q

reactivity and impulsivity predict a shift to compulsive drug-taking

A

high reactivity to novelty predicts a tendency to self-administer addictive drugs
high impulsivity rats display higher compulsive cocaine self-administration

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17
Q

biopsychosocial model of addiction

A

nature sets a dopamine level that is nurtured by social interactions
- drug exposure
- dopamine (and D2 receptor) functionality
- behavioural traits
- social factors (dominance)
all contribute to model of addiction

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18
Q

polygenecity

A

multiple genes are involved in addiction

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19
Q

predispositions

A

tendency/vulnerability to suffer from a particular condition

20
Q

link between a gene and addiction

A

genes + proteins → pharmacodynamics → physiology → behaviours

21
Q

SNPs

A

single nucleotide polymorphisms
base pair differences within coding and non-coding regions between alleles of genes in the population

22
Q

transgenerational epigenetic effect

A

methylation affects rate of transcription and gene expression → traits passed on to offspring

23
Q

studying genes

A

genome-wide association studies

dopamine networks → dopamine transporters, receptors in VTA + NAc

neuronal adhesion - important for plasticity
DNA/RNA processing
transcriptional regulation
cell structure

24
Q

addiction is viewed as a learning disease

A

addictive drugs hijack the learning/reward circuit

association between dopamine + reward → learning

25
Q

genetics x environment

A

play a 50-50 role to produce behavioural phenotypes of addiction

26
Q

routes of administration

A

inhalation (smoking)
injection (IV, IM)
insufflation (snorting)
oral (chewing tobacco, sublingual - not swallowing)
transdermal patch
ingestion

27
Q

Faster absorption routes

A

faster delivery to the brain → higher peak - more dopamine; correlated with stronger high; drug does not remain in the brain for very long

28
Q

slower absorption routes

A

peak not as high, less intense high, prolonged duration in the brain - sustained release

29
Q

bioavailability

A

amount of administered drug reaching systemic circulation

30
Q

inhalation

A

drugs cross into blood by diffusion = smaller hydrophobic drugs are absorbed the fastest
7-10 second onset
2-4 hour duration
5-99% bioavailability
shortest circulatory path to brain
huge surface area for absorption
risks: emphysema, COPD

31
Q

injection

A

10-20 second onset
2-4hr duration
i.v. = 100% bioavailability
2nd shortest circulatory path
subcutaneous and I.M absorption depends on diffusion into tissue and blood flow
risks: necrosis, track marks, infection

32
Q

insufflation

A

10-45 min onset
5-8 hr duration - extended release
up to 80% bioavailability
longer pathway to the BBB
risks (snorting cocaine): erosion of upper palate

33
Q

ingestion

A

20-45 min onset
6+ hour duration
5-99% bioavailability
first pass metabolism; stomach pH can alter chemistry, degrade
risks: irritation, emesis

34
Q

drugs must…

A

reach brain to bind receptors → effects
route affects bioavailability

35
Q

abuse potential

A

quicker onset triggers greater euphoria

very high: heroin IV, crack
very low: hallucinogens, ingested drugs

36
Q

dose response curve

A

describe relationship between drug concentration and effects

37
Q

efficacy

A

maximal response to drug
Emax

38
Q

potency

A

highest effect at lowest dose (concentration dependence)
lower ED50 = more potent

39
Q

therapeutic index

A

difference in quantitative response - beneficial vs toxic response
LD50/ED50
changes in the presence of other drugs

40
Q

synergism

A

additive effects - effect of multiple drugs is greater than individual effects

41
Q

antagonism

A

decreased overall response
compete for binding with agonist

42
Q

drug half-life

A

time to remove 50% of [drug] from circulation

43
Q

kinetics

A

describe elimination - zero order, first order
change with repeated use → tolerance

44
Q

zero order

A

linear curve of elimination

45
Q

first order

A

exponential curve of elimination

Pmcol 305 (18 decks)

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