Treatment of Addiction Flashcards
What do drugs do to the CNS?
Alter synaptic plasticity by changingg the synaptic plasticity in circuits involved in motivation & psychomotor activation -
> LTP and LTD
Explain the ADDICTION CIRCUITRY
- what system do addictive drugs target?
- drug evoked synaptic plasticity outlasts the presence of drug in the brian and contributes to the reorginisation of a neural circuit.
- Addictive drugs target the MESOCORTICOLIMBIC DOPAMINE (DA) system.
- This area exists mainly in the ventral tegmental area (VTA) and projects mainly to the nucleus accumbens (Nac) and Prefrontal Cortex (PFC)
- All addictive drugs increase dopamine (DA) concentrations in the VTA itself and in its projection areas
- Drugs of abuse potentiate the effect of electrical brain stimulation.
- Alcohol abuse can occur in the absence of dopamine activation
What are some psychoactive drugs?
Cocaine and Amphetamine
How does cocaine/amphetamines work?
increase the amount of dopamine at synapses of the nucleus accumbens by blocking the dopamine transporter and reuptake from the synaptic cleft =>
- cocaine directly inhibits the DA transporter
- amphetamines are taken up in the cell to enhance the release of DA
Causes midbrain dopamine neurons (VTA) to also release DA from their dendrites
inhibition of DA transporters increases DA in the VTA, Nucleus accumbens and PFC
How does nicotine work?
Increases the firing of DA neurons through NICOTINIC receptors expressed on DA neurons
+ stimulates presynaptic cholinergic receptors = increases the amount of DA released at synapses in the nucleus accumbens
How to opioids and canaboids work?
MUI OPIOID RECEPTOR AGONISTS
- target GABAergic interneurons in the VTA and decrease their activity
- hence take off the effect the INHIBITIOn which is on the DA neurons in the VTA.
- :. get reward because they inhibit the GABA neurons which usually act to inhibit DA release in the nucleus accumbens
- why the GABAergic neurons are targeted may be due to mu opioid receptors expression on gaba but not on DA neurons or GABAergic neurons may be more SENSITISED than DA neurons.
What are Benzodiazapines used for?
- Anxiety and sleeping disorders
- can be used in epilepsy
CHRONIC DRUG USE CAN LEAD TO ADDICTION
How do Benzodiazapines work?
Bind to GABAa receptors, potentiating the inhibitory effect of GABA
Interneurons normally INHIBIT the activity of DA neurons in the VTA
Hence potentiation of GABA causes silencing of interneurons- ie. disinhibition.
Indirectly increases activity.
Lead to addiction - addiction takes a long time to “unwind”
What is Zolpidem (stillnox) & how does it work?
Zolpidem (Stillnox) is used in insomnia and other brain disorders
It is a SHORT ACTING non-benzodiazapine hypnotic that potentiates GABA by binding GABAa receptors at the same location as benzodiazapines.
- TGA 2008: warning- used for sleep.
- Zolppidem may be associated with potentially complex sleep related behaviours which may include sleep walking, sleep driving and other bizarre behaviours.
- Reccomended doses be reduced by 2-% in 2013 because of next morning alertness impairment
Explain some of the changes psychostimulants such as COCAINE and AMPHETAMINES have to the CNS.
Psychostimulants induce neuroplasticity:- cocaine and amphetamines increase spine density & dendritic branches
: on medium spiny GABAergic neurons within the shell & core of th Nucleus Accumbens
: Glutamatergic pyramidal neurons within the PFC
-> some changes evident within 24 hours after drug administration. & persist for 3-4 months
What does repeated exposure to METHAMPHETAMINES CAUSE?
- Drug craving and relapse
- Long term persistent synaptic changes that persist long after drug withdrawal.
: Normalised after drug re-administration - Methamphetamine causes a DA release
: 10 day administration –> long lasting depression at corticostriatal terminals
: relieved by drug readministration
: both processes are due to alteration in dopamine and cholinergic receptor systems
Overview:
How do you treat alcohol addiction?
Short term?
Long term- drug names
Short term: Diazepam & VB12
Acamprosate: + psychological, physical support
Naltrexone - high compliant, no chronic pain
Disulfiram - can kill
ACAMPROSATE: indications
- maintenance of abstinence in patients with alcohol dependence. Must have additional psychological and physical support.
- should be commenced 1 week after drinking stops
- May prove to be effective for treating other psychomotor stimulant and opiate activity
- Long term benefits are unclear
ACAMPROSATE: Pharmacodynamics
Mixed antagonist of NMDA and mGLuR5 glutamate receptors
- decreases glutamatergic transmission and modulates neuronal hyperexcitability during withdrawal from alcohol.
- Reduces neuronal hyperexcitability characteristic of alcohol withdrawal
- Reduces alcoholic craving in some people
- Some of these people remain abstinent, others drink less alcohol.
ACAMPROSATE: pharmacokinetics
Contraindicated in significant hepatic or renal impairment (decrease dose)
= diarrhoea, rashes, abdo pain, nausea and vomitting.