Pharmacotherapy for Drug and Alcohol Misuse Flashcards
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?
5
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
Acamprosate
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?
B1 (thiamine)
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
Hyperemesis gravidarum
Why do alcoholics require IM or IV thiamine?
They cannot absorb sufficient from an oral route
What is the daily requirement of thiamine?
1mg
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?
Nicotine
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
Name a GABA-B agonist that can be prescribed for alcoholism
Baclofen
What is baclofen usually prescribed for?
Treating muscle spasms in multiple sclerosis
Why are opiate antagonists efficacious in alcoholism?
Opioids are inhibitory against GABA via the mu-opioid receptor - opiate antagonists block this, allowing GABA to function and block dopamine release, removing the pleasure associated with drinking
Name 2 opiate antagonists prescribed for alcoholism
Naltrexone and namlefene
Which patients cannot take opiate antagonists for alcoholism?
Those on opioid analgesia
How does alcoholism affect the mu and kappa receptors?
They are usually balanced - in alcoholics, the kappa system is upregulated, leading to feelings of dysphoria
Describe the method of action of nalmefene
It antagonises the mu and kappa opioid receptors, reducing the pleasurable effects of alcohol
State some side effects of nalmefene
Nausea, insomnia, depersonalisation - most pronounced over first few days
What is acamprosate?
An anti-glutamate drug derived from taurine
Which abstinence-maintaining drug can be started while an individual is still drinking?
Nalmefene
What is the key therapeutic approach in opiate addiction?
Substitution - either with a full opioid receptor agonist, a partial agonist, or an antagonist
Name a full opioid receptor agonist and its major side effect
Methadone - respiratory depression (a danger of all full agonists)
Name a partial opioid receptor agonist
Buprenorphine
Give at least 2 disadvantages of prescribing buprenorphine in heroin addiction
Much more expensive than methadone, less liked by heroin adducts (prevents heroin having effects when taken ‘on top’), can still cause lethal respiratory depression when taken with other depressants, causes some withdrawal symptoms
Give an advantage of prescribing buprenorphine in heroin addiction
Less sedating than methadone, safer - especially for elderly addicts as tolerance decreases with age and frailty
Give 2 disadvantages of prescribing naltrexone for heroin addiction
No reinforcement therefore poor compliance, precipitates extreme withdrawal symptoms
Which heroin addict patient group is likely to take naltrexone?
Professional ex-opiate addicts who want to continue working, e.g. dentists or doctors
Why must naloxone always be prescribed with methadone, and what is it?
It is a short-acting opiate antagonist and must be prescribed in case of overdose
Describe the symptoms of opiate withdrawal
Mydriasis, diarrhoea, dysphoria, tachycardia, sweating, insomnia, pilorection, rhinorrhoea, shivering, restlessness, craving
Other than opiate agonists, name a class of drugs which can treat opiate withdrawal
Noradrenergic agonists
Name a drug used to treat nicotine withdrawal
Varenicline
