Drug Dependence and tolerance
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What is a drug?
Any chemical compound
What is the ICD 10 criteria for diagnosis of substance dependence?
• desire or sense of compulsion • difficulties in controlling substance use • a physiological withdrawal state • tolerance • prioritising use • persisting with subtance use despite consequences
Name examples of Class A drugs
• Ecstasy • LSD • Heroin • Cocaine • Crack • Magic Mushrooms • Amphetamines (if prepared for injection)
Name examples of Class B drugs
• Amphetamines • Cannabis • Methylphenidate (Ritalin) • Pholcodine
Name examples of Class C drugs
• Tranquilisers • Some painkilers • Gamma hydroxybutyrate • Ketamine
What other conditions is drug abuse/dependence often linked with (co-morbidity)?
• Depression • Anxiety • Schizophrenia (smoking might help) • PTSD
What is the difference between psychological addiction and physical addiction?
• Physical addiction is to self-medicate withdrawal symptoms eg. dysphoria, cramping, agitation • Psychological addiction drugs of abuse activate same brain systems as natural and so are ‘rewarding’ - much more complex.
In what parts of the brain does self-stimulation act - ie the reward centres?
• Median forebrain bundle • Ventral tegmental area Also these (but less effective): • Prefrontal cortex • Nucleus accumbens
What effect does cocaine have at the dopamine nerve terminal?
• Cocaine blocks dopamine transporter (responsible for reuptake) • More dopamine in cleft binding to post-synaptic receptors • More reward/pleasure
What is the effect of amphetamine on dopamine nerve terminal?
Amphetamines can get into the cell via the dopamine transporter and displace dopamine from synaptic vesicles, so called ‘reverse transport’. They are also lipophillic and cationic so can get into cells and intracellular organelles quite easily eg. mitochondria.
How can methamphetamine abuse lead to Parkinson’s?
Loss of dopamine transporter in human methamphetamine abuser -> neurotoxic -> can lead to early onset parkinson’s.
What are the general treatments for addiction?
• Psychological mainly • Disulfiram for alcohol • Methadone replacement therapy and opioid antagonists for heroin
What are treatments for heroin dependence?
• Mu opioid receptor activity • Agonists treatment can work, but antagonist would cause terrible withdrawal symptoms (only for overdose)
Name a full agonist, a partial agonist and an antagonist for the mu opioid receptor
• Full agonist - heroin • Partial agonist - buprenorphine • Antagonist - naloxone
What are the types of drug tolerance?
• Dispositional tolerance (metabolic) • Functional tolerance (cellular) • Context-specific tolerance (environmental) • Cross-tolerance
What are the acute effects of alcohol on transmitter systems?
• Increases GABA effects • Decrease excitatory transmitters (glutamate + aspartate) • Particular effect at NMDA receptors • 5-HT transmission altered • Inc release of endogeneous opiates • Inc mesolimbic dopamine tranmission
What is the physiology of a hangover?
• Formation of acetaldehyde (metabolism of alcohol) • Dehydration • Irritant effect on GI
How does disulfiram (treatment) make you feel sick when taken with alcohol?
• Disulfiram blocks the ALDH enzyme • -> build up of acetaldehyde • toxic -> nausea
