Substance Misuse & Addictions Flashcards
What 2 distinct mechanisms does the basic science of substance misuse suggest?
Tolerance (the basis of physical dependence)
Reward centre (the basis of psychological craving)
What is tolerance?
“Reduced responsiveness to a drug caused by previous administration”
Develops in response to many types of drug
eg opioids, ethanol, barbiturates, benzodiazepines
An example of homeostasis-the body likes things the way they were
Mechanisms underlying tolerance can vary
What are the mechanisms of tolerance and some examples?
Dispositional=less drug reaches the active site, eg
- decreased rate of absorption
- increased rate of metabolism to inactive metabolites
- decreased rate of metabolism to active metabolites
- increased rate of excretion
Pharmacodynamic (aka tissue or functional tolerance) = site of action is less affected by the drug
- down-regulation or internalisation of drug receptors
- reduced signalling down stream of drug
receptors
- some other compensatory mechanism
When does tolerance become dependence?
Development of tolerance may also lead to withdrawal symptoms
Development of tolerance will in itself cause dependence – have to keep taking the drug to achieve a normal state-as if not will be imbalance between drug effect and adaptive response
What is the withdrawal phenomena?
Withdrawal effect of a drug is usually the reverse of the acute effect
Tolerance & dependence are closely linked
Development of tolerance may lead to physical dependence in order to avoid the (unwelcome) withdrawal effects
What are the acute effects and withdrawal effects of:
- Opioid
- Barbiturate
- Cocaine?
- constipation-diarrhoea
- anticonvulsant-convulsions
- elevated mood-depressed mood
What is the reward pathway and how has it evolved?
The reward pathway:
- Neurones project from the ventral tegmental area to the nucleus accumbens & prefrontal cortex
- When VTA neurones are stimulated they release dopamine is released
- This causes a sensation of pleasure/reward
Why has the reward pathway evolved?
The reward pathway is normally activated by eating, drinking and sex
It therefore encourages those “healthy” behaviours that lead to propagation of your genes
How do some drugs of abuse affect reward centres?
Some drugs of abuse tap into the reward pathway and increase dopamine levels eg
- heroin increases firing rate of dopaminergic neurones
- amphetamine increases dopamine release
- cocaine inhibits dopamine uptake
- alcohol
This produces the psychological component of addiction - “craving”
What 2 distinct components of drug dependence have been shown in animal studies?
Physical dependence which develops as a consequence of tolerance to the drug
Psychological craving which is a result of stimulation of the reward pathways in the brain
In humans it is almost certainly more complex
eg discriminative (cue) effects
What are some examples of stimulants that are abused?
Cocaine
Amphetamine
Methamphetamine
Methylphenidate (prescribed for ADHD-may misuse it if they are prescribed it)
What is the most potent natural stimulant?
Cocaine-extracted from leaves of coca plant
Cocaine (powder) and crack cocaine (smoked)
Crack produced by mixing cocaine with a base (sodium bicarbonate) and purified
How does cocaine work?
Monoamine reuptake inhibitor – dopamine,serotonin,noradrenaline increase
- Makes dopamine more available in the presynaptic space-so have sensation of rush of dopamine
What are the effects of cocaine and how long do different modes of taking it take effect?
Depends on dose and rate of entry to the brain
smoking - almost immediate
injecting - 15 to 30 secs
snorting - 3 to 5 mins
the effects of crack smoking are very intense but quickly over ( 15 mins)
EFFECTS
stimulant and euphoriant
Anaesthetic effect
Hypersensitive
increased alertness and energy
increased confidence and impaired judgement
lessens appetite and desire for sleep
If mixed with alcohol - cocaethylene-almost like cocaine with longer half life
What are the serious effects of cocaine?
damage to nose and airways (consistent vasoconstriction damages nasal septum)
convulsions with respiratory failure
cardiac arrhythmia’s and MI
hypertension and CVA
toxic confusion
paranoid psychosis
What are the cocaine withdrawal effects?
Depression
Irritability
Agitation
Craving
Hyperphagia
Hypersomnia
Broadly opposite of drug effect
How is amphetamine taken and what are the effects of taking it?
Sniffed, swallowed or injected
Effects similar to cocaine but longer lasting
Toxic confusion occasionally with convulsions and death
Amphetamine psychosis in heavy chronic use
What are some examples of opiates?
Opium
Morphine
Heroin (diamorphine)
Methadone
Codeine and dihydrocodeine
They’re all broadly, opiate agonists, often changing by exactly what opiate receptors they are hitting and half life issues as well
Heroine is available as what and what may it be presented as?
Available as diamorphine or as diamorphine hydrochloride
May be presented as powder or as an almost tar like substance
How can heroin be taken?
Taken by:
- Snorting ( not common in UK)
- Smoking(chasing the dragon)
- Injection (cultural or tolerance reasons)
Smoking is safest, injecting the most dangerous method of use
Via what receptors does heroin act and what is its half life?
Opiod agonist
Acts via mu (principally)
Acts principally via Mu ,Delta and Kappa receptors
Kappa and Delta – analgesia
Mu – mood effects, analgesia and euphoria
Half life of 30mins – multiple administrations needed if dependant ( increased risk) - subjective effect of approx. 4hrs
Sleep disturbed, acute withdrawals in the middle of the night etc
What are the effects of heroin and what can happen in an overdose of it?
Analgesia
Emotional analgesia
Nausea initially
Euphoria
Pin point pupils
Itching/sweating
Constipation
Decreased libido/menstrual irregularities
Reduced cough reflex
OVERDOSE:
Respiratory depression
Snoring indicates risk
Bradycardia
Hypotension
Death
Risk increased if mixed with other respiratory depressants – alcohol, benzodiazepines etc
What is used in a Heroin overdose?
Naloxone – opiate antagonist
National Naloxone Programme
What are the side effects of opiates?
First time - nausea/vomiting and headache
Medium term – phlebitis
-endocarditis
-Injection injuries/consequences (BBVs)
- Anorexia
- Constipation
Longer term - tolerance
- Withdrawal
- Social and health problems
BBV-Hep C most common
What are the signs of opiate withdrawal syndrome?
craving
insomnia
yawning
muscle pain and cramps
increased salivary, nasal and lacrimal secretions
dilated pupils
piloerection (hence ‘cold turkey’)
What is the role of methadone maintenance and what is its downfall?
Decriminalises drug use & allows normalisation of lifestyle
Reduces iv misuse
Leakage on to the illicit market
What is another name for diazepam?
Valium
Xanax is also known as?
Alprazolam
Benzodiazepines: What kind of agonists are they?
GABA agonists
Anxiolytics, sedatives
Ecstasy (MDMA): what are its effects?
Relaxed euphoric state without hallucinations
Majority of all ‘ecstasy tabs.’ contain no MDMA