Drugs and Addiction (Laura) Flashcards
Drug definition
A chemical substance, with a known chemical structure that. produces a biological and psychological effect when it is administered
How are drugs made?
- Can come from plants or animals
- Can be entirely synthetic
- May be the result of genetic engineering
What is the key factor that makes a drug a drug?
Needs to be something that is administered to the body rather than a natural (endogenous) substance released by the body
What is pharmacokinetics?
The branch of pharmacology concerned with the movement of drugs within the body
How does route of administration affect pharmacokinetics?
- Causes drastic differences in onset, intensity and duration of a drug’s effect
- Slower onset of drug action the more gradual the build up of the effect and the longer it will last
How is a route of administration chosen?
- Chemical characteristics of the drug
- Unprocessed drugs such as tobacco or cannabis cannot be injected only smoked, snorted and cooked - Personal preference
- Disliking sensation of inhalation - Speed with which the drug acts
How are health outcomes associated with route of administration?
- Risk of dependence - the sooner the effect of the drug is experienced the more reinforcing it is
- Susceptibility to infection - intravenous could lead to Hepatitis C
- Route specific health complications - snorting can lead to nasal ulcerations
Route of administration: Rural Vs. Urban Drug Users (study)
Young, Havens and Leukefeld (2010)
- 212 rural users vs 111 urban users
- Prescription drug. abuse (e.g OxyCodone)
- Urban users more likely to swallow drugs
- Rural most likely to snort drugs
- Alternative routes of administration were more likely in rural populations
- Linked to drug problem severity (higher in rural populations)
How does absorption into the bloodstream account for some differences in pharmacokinetics? (and distribution of drug after absorption)
- More barriers a drug has to travel through too reach the brain the slower the effect and drug more likely to be degraded
- Degree too which drug is soluble in lipids
- Degree of ionisation (ionised forms less likely to cross cellular membrane than deionise)
- Size of molecule (smaller = faster)
- Difference in drug concentration on either side of membrane
Examples of absorption at different routes of administration
- Intravenous = Little absorption, direct delivery to the blood stream and move to site of drug action
- Inhalation = Difference in chemical concentration from lung to blood stream always high, so rapid (movement down the gradient), high lipid solubility and small particles
- Mucous membrane = Several layers of cells to cross but aided by difference in concentration
- Oral = very slow, often poor because of degradation by stomach acid and enzymes
How are drugs distributed after absorption?
- Stored in body tissue
- Remains in blood stream
- Metabolised
What does an agonistic drug do to neurotransmission?
Drug that binds to receptor and switches neuron on
What does an antagonistic drug do to neurotransmission?
Drug that binds to receptor and prevents agonists from binding and neuron won’t switch on (drug blocker)
What are the monoamines?
- Neurotransmitters
- Dopamine
- Serotonin
- Norepinephrine
What are the 2 main process that contribute to drug elimination?
- Metabolism
- Excretion
- The body works actively to eliminate the drug
- Reverse of absorption
How are drugs excreted?
- Drugs can be excreted. either unchanged or as a metabolite
- Via. many different wxit routes, urine, bile, exhalation, sweat, saliva etc
- The most important organ in excretion is the kidney
- Drug molecules that cross membranes easily can be accidentally reabsorbed so products that are most easily
Mode of drug excretion: Exhalation (Lungs)
- Example of the importance of principles of diffusion
- When being excreted the concentration gradient works in the opposite direction to absorption
- Lungs should have low concentration so drug moves from blood stream to lungs
- Every time breathe out drug is excreted
How does the metabolism break down drugs?
- Breaks them down into metabolites
- Breaks them down into another chemical that can be active (can also create biological or psychological effects) or inactive
- Tends to take place in the liver
- Phase 1 (oxidation), phase 2 (conjugation) (and phase 3)
- Doesn’t always go in the expected direction
Metabolism example: Alcohol
- Alcohol is metabolised by specific enzymes in the liver
- Constant rate (170-240g per day average)
- Alcohol to acetaldehyde to acetate to water and carbon dioxide
- Important area of research is individual differences in alcohol metabolism
What is the half life of a drug?
- The amount of time it takes to eliminate half the drug
- Reflects time to metabolise and excrete
- Affects how long the effects of drug will last
- Time interval to avoid withdrawal
- Caffeine has a half-life of 3-7 hours
- Half-life can vary from person to person (e.g. weight, gender etc..)
Journey case study: MDMA (route of administration)
- Oral
- Intravenous
- Intranasally
Journey case study: MDMA (absorption)
Gastrointestinal tract
Journey case study: MDMA (Onset of action)
30 minutes
Journey case study: MDMA (Peak serum levels)
1-3 hours
Journey case study: MDMA (Distribution)
Passes readily int tissues
Journey case study: MDMA (Site of action)
- Indirect serotonergic agonist
- Increasing the amount of serotonin released into the synapse
- Enhances the release of dopamine and noradrenaline
- Can block their re-uptake
Journey case study: MDMA (Metabolism)
- In liver to an active metabolite
- Methydioxyamphetamine
Journey case study: MDMA (Excretion)
- Urine
- Unchanged drug
- Phase 1 and 2 metabolites
Journey case study: MDMA (half-life)
7 hours
What is neuroadaption?
- When we introduce drug to the brain we upset its balance
- Brain seeks to adapt to redress this imbalance by minimising the effect of the drug
- Brains version of homeostasis
What is tolerance of drugs?
- When we use a drug repeatedly the effects diminish
- We need more and more to get the same effect as when we first used it
- Tolerance is to effects of drug and not drug itself
- Applies to almst all effects associated with drugs of abuse
- Happens at different rates and to varying extents for different effects of those drugs
What effects of drugs do we usually become tolerant to the quickest?
Negative effects e.g. nausea
Tolerance case study: heroin
- Quick tolerance to nausea
- No tolerance ever to constipation or ‘pinpoint’ pupils
CROSS-TOLERANCE: Once you are tolerant to effects of heroin you are also tolerant to effects of morphine, codeine and methadone. Tolerance to effects of one drug in a class leads to tolerance of effects of other drugs in the class
What is metabolic tolerance
- Pharmacokinetic tolerance
- Body becomes better and more efficient at breaking the drug down (small effects)
Metabolic tolerance example: Alcohol
Amount of liver enzyme produced by body goes up
What is cellular tolerance?
- Pharmacodynamic tolerance
- Change in number of receptors, in receptor function and/or post-synaptic function (large effect)
Cellular tolerance example: Caffeine
- Changes in adenosine receptor signalling that oppose effects
Tolerance and drug overdose
- Overdose often happens when people are on the road to recovery
- Tolerance has gone down but individuals use a habitual amount and that habitual amount is too much following abstinence or reduction
What is sensitisation?
- Opposite of tolerance
- After repeated administration it will take less of a drug to elicit the same effect
- Cross-sensitisation can also occur e.g. cocaine and amphetamine
- Thought to be due to persistent activation of ventral hippocampus-nucleus accumbens pathway
How does physical withdrawal syndrome occur
- Due to neuroadaptation (tolerance)
- As drug wears off uncomfortable symptoms occur
- Reversed by administering drug
- Sign of physical dependence on a drug
What factors affect withdrawal?
- Pattern of drug use
- Amount of drug consumed
- Length of time using drug
- Half-life
Evidence for caffeine withdrawal study
Silverman, Evans, Strain and Griffiths (1992)
- Double-blind trial
- Two days of their normal caffeine regime
- Two days with placebo pills
- Two days with. caffeine pills
- Assessed depression level, anxiety, mood state and incidence of headaches
- Significantly higher scores in these tests in the placebo condition than in either of the other conditions
What is the withdrawal-reversal hypothesis
- When baseline cognitive performance levels are taken at the beginning of a trial, experimenters are actually misinterpreting withdrawn performance as normal
- James (1997) suggested a long term repeated measures trial with suitable ‘washout’ periods between testing
- James (1998) failed to find any net benefits of sustained caffeine usage
What is learning theory?
- Dominant approach to understanding addictive behaviour
- Helpful way of exploring non-drug addictions
Two variations:
- Learning theory
- Social learning theory
How does learning theory work?
- Operant conditioning
- Understanding behaviour in terms of rewards and punishments resulting from that behaviour
- Assumption that we will tend toward reward and avoid punishment
Positive reinforcement for drugs (operant conditioning)
- Taking the drug leads to activation of reward pathway
- Contiguity - how clearly the behaviour and the effect are linked (time)
- Routes of administration - how soon you feel effects = more reinforcing because behaviour and effect are more clearly linked (time)
Negative reinforcement for drugs (operant conditioning)
- Removal of unpleasant stimulus/discomfort
- Removal of withdrawal symptoms (nausea, headaches etc)
Punishment for drug (operant conditioning)
- Negative consequences of behaviour
- Withdrawal, health consequences
- Can often be in medium and long term in cases of addictive substances
- Often lower or low contiguity
What is conditioned tolerance?
- Drug opposite conditioned responses counteract. anticipated effects of drugs
- This may contribute to tolerance
- Attenuate drug effect
What is conditioned ‘high’ needle- freaking
Levine (1974)
- Heroin users when heroin is unavailable
- Go through ritual of preparing to inject drug but use saline (or other things) instead
- Mild ‘high’, some physiological signs, some withdrawal reversal
What is social learning theory?
- Learning always takes place within a social context (Bandura, 1977)
- Self-efficacy, the extent to which someone feels capable of an action (Bandura, 2010)
- Expectancy theory (expectation of an outcome) especially relevant in alcohol research (Jones et al 2001)
Animal model pros
Helps us to understand neuroadaptation, risk factors for addiction and development of treatments.
Animal model cons
- Led us down wasteful routes
- Many drugs based on animal models have failed.
- Animal models portray addiction as a disorder of compulsion but human evidence suggest goal-directed operant behaviour
- Addiction: dependence on language
- Cannot ignore environmental and social: hard to model with animals
What is the incentive sensitisation theory based on?
Robinson and Berridge (1993)
- Craving
- Craving and drug taking can. be re-instated after drug use has ceased
- As drugs are wanted more and more, liking may go down
What is polydrug use?
The use of more than one drug in combination
Why is there polydrug use?
- Cumulative or complementary effects: mixed to increase overall psychoactive experience
- Offsetting of negative effects of a drug
- The use of several substances by an individual over a longer period of time might reflect the replacement of one drug by another, due to changes in price, availability, legality or fashion
- Could also reflect the use of separate drugs in different settings or contexts, or simply reflect regular multi-substance use associated with drug dependence
What is the underlying neurobiology of polydrug use?
- Common neural systems
- Use of one drug leads t risk of using another
- Cocaine addict at risk of relapse from occasional heroin use and vice versa
- Rehab requires total abstinence
- Cross sensitisation exists between non-drug and drug based addictions
- Sex addicts are often addicted to alcohol or another drug
Heroin and cocaine co-use
- Negative consequences on health
- Simultaneous. use doesn’t induce novel effects
- No difference in reinforcement value, especially at high doses
- Cocaine alleviates withdrawal effects of opioid use
