Psychopharmacology 2 Flashcards
What is chlorpromazine and what are its side effects?
- Anti-psychotic
- Parkinsonism - loss of dopaminergic neurons in substantia nigra
- Bind to D1, D2
What are the indirect measures of dopamine?
- Homovanillic acid = breakdown product of dopamine
- Dopamine receptor binding
What does 18F fluorodopa uptake represent and what is it metabolised by?
- Uptake represents dopamine synthesis - increased 20% in schizophrenia
- Metabolised by DOPA decarboxylase
What does excess dopamine in the mesolimbic pathway lead to?
Positive symptoms (delusions, hallucinations)
What does hypo-activity (under-active dopamine) in the mesocortical pathway lead to?
- Positive/cognitive symptoms
- Alogia, anhedonia, apathy, amotivation, social withdrawal
What the MOA of LSD?
- Serotonin agonist
- Psychosis
- Lower expression serotonin receptors
What do NMDA (glutamate) receptor antagonists produce?
Psychosis
e.g. Ketamine
What happens to levels of glutamate in schizophrenia?
- Reduced levels in CSF
- Mainly in hippocampus/PFC
What is inhibitory interneuron dysfunction?
- GABA release inhibits excitatory neurons
- Excitatory neurons inhibit inhibitory neurons with glutamate
- Balance in health
- Loss of inhibition in schizophrenia
What is the MOA of most antipsychotics?
Dopamine antagonists
Clinical effect on mesolimbic pathway
What effect does dopamine have in the basal ganglia?
- Dopamine promotes movement
- ACh inhibits movement
- Dopamine blockade = parkinsonism
What does procyclidine do?
Balances cholinergic + dopaminergic activity in basal ganglia
What does dopamine blockade in anterior pituitary lead do?
- Disinhibition of prolactin release
- Side effects = gynaecomastia, galactorrhoea, sexual dysfunction
What affect do antipsychotics have on the myocardium?
- Block repolarisation of K+ channel
- Prolong QT interval
- Increased risk sudden cardiac death
What affect do antipsychotics have on PSNS?
Tachycardia, dry mouth, urinary retention, constipation, disrupt cognitive function, balance, delirium
What affect do antipsychotics have on M3 receptors?
- Weight gain
- Metabolic syndrome
What is neuroleptic malignant syndrome (NMS)?
- Muscle rigidity, decreased HCS, autonomic instability
Serotonin syndrome as above but hyperreflexia, dilated pupils, increased bowel sounds
How is NMS treated?
- Immediate withdrawal antipsychotics
- Dantrolene (reduce muscle spasm)
- Dopamine receptor agonist (Bromocriptine)
- ICU
What effects do recreational drugs have on dopamine?
- Increase in dopamine in nucleus accumbens
- High levels of D3 receptors
- Dopamine release in amygdala (part of memory system) during significant events
- Mediates + reinforcement
What are the psychopharmacological effects of alcohol?
- Positive modulator @ GABA receptors
- Use of BD2 in withdrawal
What are the psychopharmacological effects of opioids?
- Mu receptor agonists - analgesia, euphoria, resp depression
- Inhibits noradrenaline
- Compensatory upregulation revealed on withdrawal - insomnia, restlessness, diarrhoea
What are the psychopharmacological effects of cocaine?
- Inhibits dopamine reuptake - Na channel blocker
- Fast uptake
- Reduce dopaminergic function on chronic use
What are the psychopharmacological effects amphetamines?
Inhibits dopamine reuptake + stimulated dopamine release
What are the psychopharmacological effects of cannabis?
- Partial agonist on cannabinoid CB1 receptors (brain
- Excitatory effects (increase cortical blood flow)
- Depression of mesolimbic dopaminergic neurons
What are the psychopharmacological effects of nicotine?
- Increase mesolimbic dopamine levels
- Reduce MAO
