Pharmacotherapy for drug and alcohol misuse Flashcards
Which receptors does alcohol target?
Activates GABA-a receptor, causing Cl- influx.
NMDA antagonist. Decreased Ca2+ flux, so decreased excitation.
What happens to these systems after alcohol withdrawal?
NMDA: Much higher glutamate. Ca2+ flux, hyper excitability and cell death. (seizures etc)
GABA: Decreased activity, Mg2+ in the receptor is deficient.
What is Acamprosate and how was it used?
Evidence shows it calms the NMDA system down.
Glutamate levels were decreased in withdrawal patients on Acamprosate.
Increases abstinence rates. Also used for relapse prevention.
What is the mainstay of withdrawal treatment?
Benzodiazepines reduce signs and symptoms of withdrawal, recommended as treatment of choice.
Carbamazepine has also been shown efficacious as an alternative.
What are the main effects of alcohol damage on the brain, and how is it treated?
Malnutrition- treat with vitamin supplementation. I.V THIAMINE is key- both in metabolism and decreasing risk of excitability.
Inflammation
What are the symptoms of Wernicke Korsakoff’s syndrome?
Wernicke’s encephalopathy: -Opthalmoplegia (nystagmus)
Ataxia
Acute confusion
A medical emergency.
Korsakoff’s syndrome:
Irreversible short term memory loss in presence of normal other cognitive performance.
How does dopamine modulated pharmacotherapy act?
DRD2 levels in addiction are very low, so:
Boost DA-ergic function to reduce dysphoria, irritability.
DA-ergic ‘agonists’:
-Bromocriptine
-Disulfiram
-Methylphenidate.
-DRD3 antagonist (presynaptic, blocking it increases DA release)
How does disulfiram work?
Acetaldehyde-> Acetate blocked, so buildup of acetaldehyde. Causes nausea, flushing, headache, vomiting.
How does disulfiram increase dopamine?
Inhibits Dopamine-B-Hydroxylase. This prevents Dopamine->Noradrenaline.
This can cause psychosis, anxiety, mania.
What effect does baclofen have?
Reduces cocaine administration and response to cues
Reduces alcohol self administration
Reduces heroin self administration.
How does naltrexone work in treating alcoholism?
Antagonises u-opiate receptor, allowing GABA break to function. Less DA is released.
This decreases the pleasurable effects of alcohol, and reduces rates of relapse. You can drink whilst on it.
The main problem is the amount of people on opioid analgesia has hugely risen. This antagonist blocks this effect.
HOw does the Kappa system work?
This modulates dysphoria. As you withdraw, kappa system stays upregulated despite a neutral mu. Relapse/reinstating of consumption slightly increases mu, but kappa is seriously dysregulated.
Targeting and reducing kappa activity is important.
What is Nalmefene and how does it work?
This decreases pleasurable effects of alcohol. It reduces drinking.
However, side effects are much worse (depersonalisation, nausea, insomnia)
No opioid analgesia possible.
What is the difference between combining methadone with heroin vs buprenorphine + heroin?
Methadone: Prevents addicts getting “high” , makes them comfortable instead. However, can be overcome with more heroin.
Buprenorphine: Sticks to receptor, so heroin cannot outcompete it.
How do you treat overdose on methadone/fentanyl/heroin?
Naloxone- shorter action antagonist than naltrexone. This precipitates withdrawal.
