Drug Dependence Flashcards
How many of the adult British population have taken illegal drugs?
One in three
What is addiction?
Chronic disease characterised by drug seeking and use that is compulsive, or difficult to control, despite harmful consequences.
Define drug abuse.
A pattern of drug use in which the users consume the substance in amounts or using methods which are directly or indirectly harmful to themselves or others.
Define drug dependence.
An adaptive state that develops after repeated drug use and which results in withdrawal symptoms upon cessation of drug use.
Define drug tolerance.
The diminishing effect of a drug which results after repeated administration at a set dose.
Define psychological dependence.
Dependence that involves emotional–motivational withdrawal symptoms (e.g. dysphoria, depression, anhedonia, restlessness).
Define physical dependence.
Dependence that involves significant physical–somatic withdrawal symptoms (e.g. fatigue, nausea, seizures, pain, delirium tremens).
Classification of drugs under the Misuse of Drugs Act 1971 - give examples for class A, B and C.
Class A: heroin, methadone, cocaine, crack cocaine, ecstasy, LSD, magic mushrooms, methadone…
Class B: amphetamines, barbiturates, ketamine, methylphenidate, codeine, cannabis…
Class C: anabolic steroids, benzodiazepines, gamma hydroxybutyrate, gamma butyrolactone, khat…
What are the receptors for…
Opiates?
Cocaine?
Amphetamine?
Mu and delta opioid receptors - agonist
DA, NAd and 5-HT uptake systems - antagonist
Monoaminergic transmission:uptake systems - agonist of TAAR1
What are the receptors for…
Ethanol?
Nicotine?
Cannabinoids?
GABA A and NMDA receptors - modulator
Nicotinic receptors - agonist
CB1 receptors - agonist
What are the receptors for…
Ketamine and phencyclidine?
Hallucinogens?
Barbiturates and benzodiazepines?
NMDA glutamate receptors - antagonist
5-HT 2A receptors - agonist
GABA A receptors - agonist
What neurotransmitter is particularly important in pleasure?
Dopamine - occupancy of dopamine receptors by labelled marker decreases when the stimulant induces pleasure, as it is displaced by dopamine.
The dopaminergic projection from _____ to _____ is essential in drug dependence.
Ventral tegmental area
Nucleus accumbens
What are the four stages of the addiction cycle?
- Intoxication – positive reinforcement. Impaired self-awareness.
- Bingeing - loss of control.
- Withdrawal/negative affect - negative reinforcement. Amotivation and anhedonia.
- Craving – conditioned positive and negative reinforcement. Drug expectation and attention bias.
Mechanisms underlying withdrawal.
Activation of kappa opioid receptors (endogenous receptor for dynorphin-like peptides) can trigger dysphoria, by reducing dopamine release. Administration of drugs of abuse increases the release of dopamine. Chronic intake leads to up-regulation of dynorphin, which might inhibit drug-induced dopamine release. After stopping the drug, these adaptations remain unopposed which contributes to the negative emotional state associated with drug withdrawal.
Brain areas involved in the development of drug dependence. (6)
Ventral tegmental area Nucleus accumbens (one of first to be involved) Insula Hippocampus Prefrontal cortex Amygdala (last to be involved)
Brain connectivity changes occurs during the development of addiction. There is gradual involvement of many CNS structures. There is increasing ________ with increasing use of drugs, and increasing ______/________.
Neuroplasticity
Compulsivity/loss of control
In addicts what can be said about the availability of dopamine D2 receptors and cerebral metabolism?
In what brain area is this particularly prevalent?
Reduced - these have a linear relationship, they increase/decrease with each other.
Orbitofrontal cortex and cingulate gyrus
In addicts, there are processes that are impaired. These include:
Self-control, emotional regulation, motivation, attention, memory, decision making, insight and salience attribution.
What area of the brain is this associated with?
Prefrontal cortex
Addicts show iRISA. What does this stand for?
Impaired response inhibition and salience attribution
Chronic drug abuse affects gene regulation. How?
Gradual accumulation in gene expression changes.
Which opiates and psychostimulants can particularly effect neuronal structure? What effect do they have?
Cocaine and morphine
Morphine decreases the total dendritic length and dendritic spine density. Cocaine increases it.
What classifies as hazardous drinking?
Regular consumption of over 5 units a day for men and over 3 units a day for women.
What does acute alcohol intoxication cause?
Euphoria followed by depressed mood, slurring of speech, ataxia, general incoordination, and pupillary dilatation.
How does acute alcohol ingestion affect transmission?
Depresses excitatory transmission and potentiates inhibitory transmission.
What is the long term consequence of alcohol abuse on the brain?
Shrinkage of grey matter
What are some of the long terms effects of alcohol abuse?
Peptic ulcer, GI haemorrhage, varices Pancreatitis Alcoholic liver disease Peripheral neuropathy Korsakoff syndrome AF Hypoglycaemia Thiamine deficiency etc etc...
What does MDMA stand for?
Methylene dioxymethamphetamine - ecstasy
What are some of the systems and receptors that MDMA target? (5)
5-HT uptake system Dopamine uptake system 5-HT2 receptors H2 histamine receptors α2 adrenergic receptors
What mediates the behavioural actions and temperature effects of MDMA?
5-HT
Psychomotor effects of MDMA are mediated by ____ stimulation of dopamine release and activation of _________ receptor.
What are these motor effects?
5-HT
5-HT 1B receptor
Repetitive movements and hyperlocomotion
MDMA users (for a median of 3.66 years) - what effect is seen on their regional glucose metabolism? What does this cause?
Significantly decreased (prefrontal hypometabolism) Verbal memory deficits
What are the signs and symptoms of acute MDMA toxicity? (6)
Body temperature elevation Disseminated intravascular coagulation Rhabdomyolysis (blocked by dantrolene) Increased renal reabsorbtion of water Hyponatraemia Cerebral oedema
What three factors determine the development of addiction?
Environment
Drug-induced effects
Genes
Overuse of MDMA leads to loss of what type of axon?
Serotonin axons
CB 1 receptors are concentrated in which part of the body?
Central nervous system
CB 2 receptors are concentrated in which part of the body?
Immune system
What type of receptor is CB 1?
G protein-coupled
What are the symptoms of cannabinoid intoxication?
Hypothermia
Rigid immobility
Decreased motor activity
Cannabinoids exert mainly what type of effect?
Inhibitory
What are the risks of long-term cannabis use?
Increases risk of developing schizophrenia and major depression, memory problems and paranoia.
What is cannabidiol?
Major non-psychotropic cannabinoid compound present in the plant Cannabis sativa
What two things does Sativex combine? What ratio?
THC and CBD
1:1
What is nabilone?
Synthetic analogue of THC
What ratio does Cannador combine THC and CBD in?
2:1
What are the key methods of management of addiction? (5)
Detoxification Psychological support Medication Evaluation and treatment for co-occurring mental health problems Long-term follow-up
What is nalmefene used for?
Reduction of alcohol consumption (opiate antagonist)
What is ceftriaxone? What has it shown potential to do?
Antibiotic
Attenuate cocaine relapse after abstinence
Why is disulfiram given to alcoholics? How does it work?
To prevent relapse
It is a aldehyde hydrogenase inhibitor, allows build up of acetaldehyde (toxic product).
Why are GABA agonists such as benzodiazepines and anti-epileptic agents given to alcoholics?
To help withdrawal symptoms
What kind of drug is naltrexone? What about acamprosate? Why is it given to alcoholics?
Opioid antagonist (also given to opiate addicts)
Affects glutamate receptors
To prevent relapse
Bupropion – what is it used for? How does it work?
Monoamine reuptake inhibitor for smoking cessation
Buprenorophine – what is it used for? How does it work?
Opioid mu receptor partial agonist, kappa antagonist to help with opiate withdrawal symptoms.
Clonidine and lofexidine – what are they used for? How do they work?
Alpha-2 adrenoreceptor agonists to help with opiate withdrawal symptoms.
What drug was recently introduced for nicotine addiction? How does it work?
Varenicline (α4β2 selective partial agonist
at nicotinic receptors)
What are the two main side effects of varenicline?
Nausea and psychiatric disturbances
