Flashcards in Pharmacotherapy for Drug and Alcohol Misuse Deck (50)
State the four uses of pharmacotherapies in addiction
Substitution, treating withdrawal, preventing relapse, and preventing harms
What percentage of alcohol dependent patients are not treated? (Kohn et al, 2004)
92% - mostly as they do not seek treatment
Are substitutions ever prescribed for alcohol?
No - but theoretically diazepam or valium could be, as they are very similar in their effects
Why should alcoholics not go cold-turkey outside of hospital?
Alcohol withdrawal is life-threatening and they could suffer seizures
How many major subunits does the GABA-A receptor have?
How does chronic drinking affect the GABA-A receptor?
It causes receptor tolerance, probably by changing the subunit profile
How does chronic drinking affect the NMDA receptor?
Alcohol antagonises the NMDA receptor. Chronic drinking leads to receptor upregulation to combat the antagonistic affect - in animal models, this is associated with impaired memory
Describe the effects of alcohol withdrawal on the brain
It increases activity in the NMDA receptor and L-type calcium channels, leading to calcium influx, hyper-excitability, and cell death. This increased activity causes seizures. It also causes decreased GABA-ergic activity and less magnesium ion inhibition of the NMDA receptor
Describe the effect of multiple alcohol detoxifications
Multiple detoxifications are associated with less response to treatment (Malcolm et al, 2000) and worse performance on cognitive tests (Duka et al, 2003)
Name a drug used at specialist addiction treatment centres to calm NMDA activity during alcohol withdrawal
Name the 2 drugs used to reduce signs and symptoms of alcohol withdrawal
Benzodiazepines and carbamazepine
Why is carmabazepine not used for alcohol withdrawal in the UK?
It side effects - confusion and ataxia - are the same as the symptoms of alcohol withdrawal
State some harms of long-term alcohol use
Malnutrition, liver disease, inflammation, Marchiafava-Bignami disease, central pontine myelinosis
What is Marchiafava-Bignami disease?
Corpus callosum demyelination, necrosis, and atrophy, lrading to loss of consciousness, aggression, seizures,depression, hemiparesis, ataxia, apraxia, and coma
What is central pontine myelinolysis?
A neurological condition involving severe damage to the myelin sheath of nerve cells of the pons. It is most commonly caused iatrogenically by increasing serum sodium of a hyponatraemic patient too quickly - the mechanism of damage in alcoholism is unclear
What is the most common vitamin deficiency in alcoholics?
State the 2 main consequences of thiamine deficiency
Wernicke's encephalopathy and Korsakoff's syndrome
Describe the triad of symptoms in Wernicke's encephalopathy
Ophthalmoplegia, ataxia, acute confusion (many patients do not have all three)
Describe Korsakoff's syndrome
Irreversible short-term memory loss in the presence of otherwise normal cognitive peformance
What is the most common presenting symptom of Wernicke's encephalopathy?
Acute confusion - which makes it hard to differentiate from acute alcohol intoxication
State a cause of Wernicke's encephalopathy other than alcoholism
Why do alcoholics require IM or IV thiamine?
They cannot absorb sufficient from an oral route
What is the daily requirement of thiamine?
Describe the relationship between the D2 receptor, D3 receptor, and addiction
Low levels of D2 are associated with drug-liking and impulsivity and are seen in stimulant and alcohol addicts. High levels of D3 are seen in stimulant addicts but not alcoholics
Which drug of addiction is bupropion licensed for?
Describe the mechanism of action of disulfiram
It inhibits aldehyde dehydrogenase in the liver, causing a buildup of the alcohol breakdown product acetaldehyde and leading to nausea, vomiting, flushing, palpitations, headache, and hypotension
State some contraindications for prescribing disulfiram
Psychosis, severe liver disease, severe cardiac disease, epilepsy
How can disulfiram cause psychiatric side effects, and what are they?
It inhibits aldehyde hydrogenase, which is in the same family as dopamine-B-hydrozylase - the enzyme which converts dopamine to noradrenaline. It hence increases the amount of dopamine and decreases noradrenaline, leading to anxiety, mania, psychosis, and depression
Why are GABA-B agonists efficacious in alcoholism?
GABA inhibits dopamine firing in response to a stimulus and hence removes the pleasure associated with drinking